Mock Electronic Case Report Forms (ecrfs) and Instructions

Transcription

1 Site Number - Enrollment Number A Randomized Trial of Enteral Glutamine to Minimize Thermal Injury Human Research Protection Office (HRPO) Log Number A HRPO Proposal Number Clinical trials.gov ID #NCT Mock Electronic Case Report Forms (ecrfs) and Instructions Please direct questions to: Rupinder Dhaliwal Project Leader Tel: ext Fax: dhaliwar@kgh.kari.net Version: March 26,

2 Table of Contents Mock CRF Page/Description Page # General Instructions 3 Screening Inclusion 5 Screening Exclusion 7 Pre-randomization 9 Randomization 9 Baseline 11 Severity of Burn Assessment 13 Study Intervention Timing 13 Nutrition Assessment/Timing 15 Daily Monitoring 17 Daily Organ Dysfunction 19 Daily Laboratory 21 Daily Nutrition 23 Blood Sampling for Mechanistic Studies (Optional by Site) 25 Burn Related Operative Procedures 27 Blood Products 29 Concomitant Medications 31 Antibiotics, Antifungals & Antivirals 33 Microbiology 35 Invasive Mechanical Ventilation/Dialysis 37 Hospitalization Overview 39 Follow-Up 39 Comments 41 Investigator Confirmation 43 Protocol Violation 45 Version: March 26,

3 General Instructions The following mock case report forms have been developed to assist the research coordinator at the participating site with data collection. The research coordinator may choose to record the data from the patient s medical chart (source document) on these forms before entering the data on to the electronic data capture system i.e. REDCAP. Alternatively, she/he may choose to use her/his own worksheets or enter data directly from the medical chart. In any case, the instructions on each page that detail how and when the data is to be collected must be reviewed. te: The appearance of these mock CRFs and the order in which they appear may vary slightly from REDCAP. 1. To help you keep track, we recommend numbering the worksheets using both the site number and the 4 digit patient randomization number assigned by the web-based Central Randomization System (CRS) on the top right hand corner of every page. 2. There may be occasions when data is unavailable, not applicable or not known for a variety of reasons. The measurement may not have been taken, the test not done, or the data may be missing from the source document. Example: T-Bilirubin was not done on a particular study day. Example: A particular data point was NOT entered in the medical chart. Or ICU flow sheet is missing. If the data is t Available for any reason, indicate by checking the box on the worksheet and on REDCAP. 3. Date format will be day-month-year, entered as dd/mmm/yyyy. For example: 08 Mar All times should be recorded using the 24 hour (military) clock. Midnight is to be entered as 00:00 hrs. 5. Anywhere in the CRF worksheet that is indicated, there must be an entry in REDCAP (in the space provided) describing what other means. 6. Study days MUST be defined as follows: Study Day 1 = ICU admit date (not randomization) and time until 23:59 that day Study Day 2 = the subsequent day starting at 00:00 to 23:59 and so on for other days. Example 1: A patient is admitted to unit on March 8 02:00. The study days would be: Study Day 1= 02:00 to 23:59 Study Day 2 = 00:00 to 23:59 and so on Example 2: A patient is admitted to the unit on March 8 14:00. The study days would be: Study Day 1= 14:00 to 23:59 Study Day 2 = 00:00 to 23:59 and so on 7. The duration of data collection and frequency will vary depending upon each Electronic Case Report Form and is outlined as follows: To be collected once: Baseline, Initial Burn Assessment, Nutrition Assessment/Timing, Final Burn Assessment, and Hospitalization Overview & Follow-Up. To be collected from Study Day 1 (ICU admission) until 10 days post last successful grafting, or until ICU/burn unit discharge, or 6 months from ICU admission, whatever comes first: Daily: Daily Nutrition, Burn Related Operative Procedures, Blood Products, Concomitant Medications, Antibiotics/ Antifungals/Antivirals & Microbiology. While patient is mechanically ventilated: Daily from Study Day 1 through Study Day 14 and then weekly: Daily Organ Dysfunction and Daily Laboratory. To be collected from randomization until 7 days post last successful grafting, or until ICU/burn unit discharge, or 6 months from ICU admission, whatever comes first: Daily: Daily Monitoring (dose of study intervention received) To be collected Weekly/other specified intervals: Nutrition Assessment/Timing (weekly prescriptions) and Blood Sampling for Mechanistic Studies (per instructions IF participating in Optional Blood Sampling).. Refer to specific instructions for each worksheet. Version: March 26,

4 Screening - Inclusion Instructions The following pages from page 4-9 inclusive, refer to the data to be entered into the Central Randomization System (CRS). When you are ready to screen and/or randomize a patient, transfer the data from these worksheets into the CRS at the following link: Refer to Implementation Manual for further instructions regarding the CRS Date and time of screening Inclusion Criteria 1. Presence of either 2nd or 3rd degree burns (or both) requiring grafting Enter the date and time you screen the patient. Only patients who meet the inclusion criteria should be entered into the Central Randomization System (CRS). Eligibility must be confirmed by the Site Investigator/ delegate. The presence of deep 2nd degree and/or deep 3rd degree burns requiring grafting is an assessment that must be made by the attending surgeon/physician. Check the box indicating that this criteria is met. This information must be obtained from the attending surgeon/delegate before randomization can occur. 2. Age Enter the age of the patient in years at the time of screening (patients must be > 18 years of age to be eligible to participate in The RE-ENERGIZE Study). 3. Presence of Inhalation Injury Indicate if the patient has an inhalation injury by placing a check in the corresponding box or Smoke inhalation injury is defined as: restricted to injury below the glottis caused by products of combustion. Diagnosis of inhalation injury requires both of the following: 1) history of exposure to products of combustion 2) bronchoscopy revealing one of the following below the glottis evidence of carbonaceous material signs of edema or ulceration te: Answering to this question does not necessarily exclude the patient from the study, refer to the Eligibility Requirements listed under Inclusion Criteria #4. 4. Total Burn Surface Area (TBSA) % Record the total burn surface area expressed as a percentage (This assessment is to be made by the attending surgeon/physician based on her/his clinical judgment). Record TBSA in the nearest whole number rounding up from 0.5 and down from 0.4; i.e. if 47.5% is reported, record as 48% and if 47.4% is reported, record as 47%. Eligibility Requirements: Patients years of age without inhalationa injury and with TBSA > 20%. Patients years of age with inhalationa injury and with TBSA > 15%. Patients > 60 years of age (with or without inhalationa injury) and with TBSA > 10%. This information must be obtained from the attending surgeon/delegate before randomization can occur. Consent must be obtained within 72 hours of admission to the ICU (burn unit). Refer to exclusion criteria for more details. Version: March 26,

5 Site Number - Enrollment Number Screening Inclusion Date and time of Screening D D M M M Y Y Y Y H H : M M (24 hour clock) Inclusion Criteria 1. Presence of Deep 2nd and/or Deep 3rd degree burns requiring grafting 2. Age years 3. Does the patient have an inhalation injury? 4. Total Burn Surface Area (TBSA): % Eligibility Requirements: Patients years of age without inhalation injury TBSA 20% Patients years of age with inhalation injury TBSA 15% Patients > 60 years of age (with or without inhalation injury) TBSA > 10% Version: March 26,

6 Screening Exclusion Instructions Exclusion criteria Record all exclusion criteria that the patient meets. If any one of the twelve criteria below are met, then the patient is NOT ELIGIBLE. 1. >72 hours from admission to ICU to time of consent 2. Patients < 18 years of age (Age of maturity for an eligible patient to give consent is 18 years in Canada and U.S.) 3. Liver cirrhosis Child s Class C liver disease (see chart below) The Child s Class C score is obtained by adding the points for all 5 criteria in this table. Any patient having a score of falls into Group C (severe hepatic impairment), which would be considered exclusion for this study. Criteria Total Bilirubin SI units Serum Albumin SI units Prothrombin time or INR 4. Pregnancy Urine/blood tests for pregnancy will be done on all women of childbearing age by each site as part of standard of ICU practice. 5. Absolute contra-indication for Enteral Nutrition Intestinal occlusion or perforation, abdominal injury. Being NPO is not considered a contraindication for Enteral Nutrition. 6. Patients admitted > 48 hours post burn Patients admitted more than 48hrs post burn (for patients that receive standardized burn care and resuscitation prior to admission to ICU, this exclusion criteria may be extended to more than 96 hrs post burn; if this is the case consent must be obtained within 24 hours of admission to burn ICU, according to the judgement of the Site Investigator) 7. Patient with injuries from high voltage electrical shock 8. Patient who is moribund. This may be defined as not expected to be in the ICU for more than 48 hours due to imminent death. 9. Patients with extreme body size: BMI <18 or >50 kg/m Enrollment in another industry sponsored ICU intervention study Co-enrollment in academic studies will be considered on a case by case basis. 11. Received glutamine supplement for > 24 hours prior to randomization 12. Known allergy to maltodextrin, cornstarch, corn, or corn products Points assigned < 2mg/dL or 2-3 mg/dl or > 3 mg/dl or < 34 μmol/l μmol/l > 51 μmol/l > 3.5 g/dl or > 35 g/l < 4 seconds g/dl g/l 4 6 seconds < 2.8 g/dl or < 28 g/l > 6 seconds < > 2.3 Ascites* Absent Slight Moderate Encephalopathy ne Moderate Severe * Refer to ultrasound results. If ascites has been drained in the past, it should be considered Moderate. If the patient does NOT meet any of the above exclusion criteria, patient is eligible for randomization and you may proceed to the Pre-randomization/Randomization form. Version: March 26,

7 Site Number - Enrollment Number Screening Exclusion Exclusion Criteria 1. >72 hours from admission to ICU to time of consent 2. Patients < 18 years of age 3. Liver cirrhosis Child s Class C liver disease 4. Pregnancy 5. Absolute contra-indication for EN 6. Patients admitted to ICU > 48 hrs post burn (if field treated > 96 hrs) 7. Patients with injuries from high voltage electrical shock 8. Patient who is moribund 9. Patients BMI < 18 or > 50 kg/m Enrollment in another industry sponsored ICU intervention study (co-enrollment in academic studies will be considered on a case by case basis) 11. Received glutamine supplement for >24 hours prior to randomization 12. Known allergy to maltodextrin, cornstarch, corn, or corn products Version: March 26,

8 Pre Randomization / Randomization Instructions General Instructions If inclusion criteria are present AND no exclusion criteria are met the patient is considered eligible for randomization into the study. Check all appropriate boxes on this form. Patient Eligibility Confirmed by MD Patient co-enrolled in another academic ICU study Consent Enter the name of the physician who confirmed patient eligibility. This individual should be listed on the Site Delegation of Authority Log. Is the patient co-enrolled in another academic ICU study, or? If, then enter the name(s) of the study(ies). Did you obtain consent? or. If YES, enter date and time of consent. If NO, choose the most important reason why the patient wasn t randomized: Reason next of kin or substitute decision maker Refused Consent Missed the patient Language Barriers t approached for consent Family dynamics Pharmacy not available Workload Issues Other Description The SDM or legally acceptable representative was not available for consent discussion within the required time frame. The SDM or LAR refused participation. It is important to document the reason for the refusal to consent. The patient was not identified by the site coordinator in time to approach for consent. Example: the patient was admitted over a long weekend. The SDM was not approached because of language barriers. A certified translator was not present. The SDM was not approached due to emotional stress or complicated family dynamics. The pharmacy not available to prepare the investigational product. There was inadequate Research staff present to follow the patient Specify the reason(s) for not obtaining consent that is not listed above. Example: patient received glutamine for >24 hrs before randomization Randomization Date and Time Log onto the Central Randomization System (CRS) to obtain the date and time of randomization. Refer to the CRS & REDCAP Manual for details. Pharmacy/Unblinded Staff tification Record the date and time that pharmacy/un-blinded staff was notified. Pre Burn Weight Use patient s pre-burn weight to avoid fluctuations due to large fluid shifts. Indicate by placing a whether the weight is: measured (obtained by a weighing scale) estimated (obtained verbally from a healthcare professional or family) Record weight in kg (to the nearest decimal point). Version: March 26,

9 Site Number - Enrollment Number Pre Randomization Patient Eligibility Confirmed by: Name of Physician: Is this patient co-enrolled in another academic ICU study? If, specify Did you obtain consent? If Date and time of Consent D D M M M Y Y Y Y H H : M M (24 hour clock) If, choose the most important reason the patient wasn t randomized next of kin or substitute decision maker Refused consent Missed patient Language barriers Pharmacy not available Workload issues Other, please specify: t approached for consent family dynamics Randomization Date and time of randomization D D M M M Y Y Y Y H H : M M (24 hour clock) Date and time pharmacy / un-blinded staff notified D D M M M Y Y Y Y H H : M M (24 hour clock) Pre-burn weight measured estimate. kg Version: March 26,

10 Baseline Instructions General Instructions Complete all of the information by placing a in the appropriate box and filling in the required boxes for each field on this form. Duration of Data Collection Sex Ethnic Group APACHE II These data are to be collected once, at baseline. Place a in the appropriate box (male or female). Tick only one box. Choose the appropriate patient ethnicity from the following list: White Black or African American Hispanic Asian or Pacific Islander Native Other (please specify) Go to the following website to calculate the APACHE II score. Record the calculated score. Reminder to use variables within the first 24 hrs of this ICU admission. If variables are not available from the first 24 hrs, go outside the 24 hr window and use data closest to ICU admission. NOTE: ensure that the units that you are using for serum sodium, potassium and white blood count are correct. Comorbidities Enter all comorbidities present using the taxonomy provided (Appendix 2). Only those comorbidities found on the taxonomy listing should be recorded. If no comorbidities are present, record this as 00. Tobacco use Alcohol use Height BMI in kg/m 2 Date and time of burn Type of burn Hospital admit ICU admit Indicate whether the patient is a current smoker or uses tobacco, or. If you are not able to obtain this information, place a in the t Available box. Indicate whether the patient has a history of alcohol abuse, or. If you are not able to obtain this information, place a in the t Available box. Place a if height is measured (by yourself or other staff); estimated (obtained verbally from a healthcare professional or family); or unknown as it is not available in the patient chart or can t be estimated. Before selecting this option please discuss with family to see if they are aware. Record height (to the first decimal point). Place a in the appropriate measurement scale (inches or meters). A Body Mass Index must be calculated to determine eligibility. Body Mass Index is calculated as: Weight in kg/height in metres 2 (metric system) Enter the date and time the burn injury trauma occurred. If the time of the burn is not available place a in the time available box. Select the type of burn that best describes the nature of the burn injury from this list (select only one): scald fire chemical radiation unknown other (please specify) Enter the date and time of hospitalization. This is the time of initial presentation to the emergency department or hospital ward, whichever is the earliest. If the patient is admitted directly to the ICU, this date and time becomes the Hospital admit date and time. If the admit time is not available, enter the time of the first documentation. Enter the date and time of ICU admission. If the patient is admitted directly to the ICU, this date and time is the same as the Hospital admit date and time. If the admit time is not available, enter the time of the first documentation. Version: March 26,

11 Site Number - Enrollment Number Baseline Sex Male Female Ethnic Group White Black or African American Hispanic Asian or Pacific Islander Native APACHE II Comorbidities Tobacco use t Available History of Alcohol abuse t Available Height measured. inches estimate meters unknown BMI. kgs/m 2 Date and time of burn D D M M M Y Y Y Y H H : M M (24 hour clock) time available Type of burn scald fire chemical radiation unknown Other specify Hospital Admit Date and Time H H M M (24 hour clock) ICU Admit Date and Time H H M M (24 hour clock) Version: March 26,

12 Severity of Burn Injury Assessment Instructions General Instructions Date of initial assessment Initial Assessment An initial assessment of the burn injury must be made by the attending surgeon/delegate within 24 hrs of randomization. This is to be repeated once at the end of the study duration i.e. 10 days post last successful grafting, or at hospital discharge, or 6 months from ICU admission, whatever occurs first. Record the date of the initial assessment done by the attending surgeon/delegate. This must be done within 24 hours of randomization. Within 24 hours of randomization, have the attending surgeon/delegate provide an initial assessment of the following using the Lund-Browder chart (see Appendix 1): superficial partial thickness burn (defined as expected to heal within 21 days without skin grafting) as %TBSA deep partial/full thickness burn (defined as expected to require skin grafting) as % TBSA Date of final assessment at discharge Record the date of the final assessment done by the attending surgeon/delegate. This must be done 10 days post last successful grafting, or at hospital discharge, or 6 months from ICU admission, whatever occurs first. Final Assessment Have the attending surgeon/delegate assess the % of area of the initial burned surface that required grafting as %TBSA Study Intervention Timing General Instructions Study intervention is to be started within 2 hours of randomization. Duration of Data Collection Study Intervention Start Date and time Study Intervention started more than 2 hours from Randomization Study Intervention Stop Date and time This data are to be collected when study supplements are first started and when study supplements are finally stopped. Enter the date and time study supplements were first started in the format dd/mmm/yyyy. Indicate or by placing a in the corresponding box. If the intervention starts after 2 hrs from randomization, you must provide an explanation in the space provided. Enter the date and time study supplements were finally stopped in the format dd/mmm/yyyy. The stop date should be at the end of the study period i.e. 7 days after the last successful grafting operation or at discharge from ICU/burn unit or 6 months from ICU admission, whatever occurs first. Laboratory Units General Instructions Complete all of the information by placing a in the appropriate box. Duration of Data Collection Laboratory Units These data are to be collected once, at baseline. Indicate the units each laboratory test is reported in by placing a in the appropriate box. Version: March 26,

13 Site Number - Enrollment Number Severity of Burn Assessment INITIAL ASSESSMENT to be done within 24 hours of randomization Date of initial assessment Superficial Partial thickness burn (expected to heal) %TBSA Deep partial/full thickness burn (expected to require grafting) %TBSA FINAL ASSESSMENT to be done 10 days post last successful grafting or at hospital discharge Date of final assessment Area of initial burned surface that required grafting %TBSA Study Intervention Timing Date and Time Study Intervention actually Started H H : M M (24 hour clock) Was Study Intervention started > 2 hours from Randomization? If, please explain why: Date and Time Study Intervention actually Stopped H H : M M (24 hour clock) Laboratory Units T- bilirubin mg/dl µmol/l Blood Sugar mg/dl mmol/l Lactate mg/dl mmol/l Ammonia µg/dl µmol/l Urea mg/dl mmol/l Platelets 10^3/µL 10^9/L Serum Creatinine mg/dl µmol/l Albumin g/dl g/l WBC 10^3/µL 10^9/L Version: March 26,

14 Nutrition Assessment/Timing Instructions General Instructions These data are collected to determine how well the patient is being fed i.e the nutritional adequacy (% calories and protein received/prescribed) and the timing of initiation of nutrition. Prescribed Energy and Protein needs Contact your dietitian to obtain this information. These will need to be calculated by the dietitian at baseline (ICU admission or at the first dietitian assessment) and thereafter. Prescribed energy needs are to be calculated by using one (or a combination) of these methods: 1) Measured Energy Expenditure (MEE) by Indirect Calorimetry (preferred option), if available MEE X ) Basal Energy Expenditure (BEE) using Harris-Benedict Equation as follows: BEE Women: ( 9.6 x weight in kg ) + ( 1.8 x height in cm ) - ( 4.7 x age in years ) BEE Men: 66 + ( 13.7 x weight in kg ) + ( 5 x height in cm ) - ( 6.8 x age in years ) If 50% Burn Surface Area, use BEE x If < 50% Burn Surface Area, use BEE x ) Predictive equations such as Carlson et al 1992 or Milner et al Refer to the Standardization of Nutrition Practices document (Implementation Manual) for more details Use pre-burn weight. For Obese patients, if your standard practice is to adjust weight for obesity, use the weight you would use. If not, use ideal body weight. Please ask you dietitian for more details. Prescribed Protein needs are to be calculated by using the following: If > 50% burns, use 2g/kg/day to 3g/kg/day If < 50% burns, use 1.5 g/kg/day to 2 gm/kg/day Use pre-burn weight. For Obese patients, if your standard practice is to adjust weight for obesity, use the weight you would use. If not, use ideal body weight. Please ask you dietitian for more details. If the prescribed energy or prescribed protein intake changes from week to week, record this in the appropriate row (Assessment #2, #3, etc) and record the date the prescription changed. In the event that the prescription changes more than once a week, record the average prescribed calories and protein over the week. If there are no changes in the prescription from baseline, place a check in the change from baseline box. Enteral Nutrition Parenteral Nutrition If the patient did not receive enteral nutrition during this ICU admission, place a in the box titled Never received during this ICU admission. If the patient received Enteral nutrition, record the following: the start date and time of enteral nutrition. the stop date and time of enteral nutrition. This refers to the date enteral nutrition was permanently discontinued, not stopped for temporary interruptions. If enteral nutrition is continued beyond ICU/burn unit discharge, record ICU/burn unit discharge date and time as the date and time that enteral nutrition was stopped. If the patient is still receiving enteral nutrition in the ICU/burn unit at 6 months, place a in the box titled Still on EN at 6 months in ICU/burn unit. If the patient did not receive parenteral nutrition during this ICU admission, place a in the box. If the patient received parenteral nutrition, record the following: the start date and time of parenteral nutrition. the stop date and time of parenteral nutrition. This refers to the date parenteral nutrition was permanently discontinued, not stopped for temporary interruptions. If parenteral nutrition is continued beyond ICU/burn unit discharge, record ICU/burn unit discharge date and time as the date and time that parenteral nutrition was stopped. If the patient is still receiving parenteral nutrition in the ICU/burn unit at 6 months, place a in the box titled Still on PN at 6 months in ICU/burn unit. Version: March 26,

15 Nutrition Assessment/Timing Date baseline prescription made - Site Number Enrollment Number Baseline Assessment Prescribed energy needs kcal Prescribed protein needs grams change from baseline Date 2nd prescription made Assessment # 2 Prescribed energy needs kcal Prescribed protein needs grams change from Assessment #2 Date 3rd prescription made Assessment # 3 Prescribed energy needs kcal Prescribed protein needs grams change from Assessment # 3 Date 4th prescription made Assessment #4 Prescribed energy needs kcal Prescribed protein needs grams change from Assessment #4 Date 5th prescription made Assessment # 5 Prescribed energy needs kcal Prescribed protein needs grams change from Assessment #5 Date 6th prescription made Assessment # 6 Prescribed energy needs kcal Prescribed protein needs grams Enteral Nutrition Never received during this ICU admission Date and time enteral nutrition started Date and time enteral nutrition stopped Parenteral Nutrition Never received during this ICU admission Still on EN at 6 months in ICU/burn unit H H : M M (24 hour clock) H H : M M (24 hour clock) Still on PN at 6 months in ICU/burn unit Date and time parenteral nutrition started H H : M M (24 hour clock) Date and time parenteral nutrition stopped H H : M M (24 hour clock) Version: March 26,

16 Daily Monitoring General Information These data are collected to determine the compliance to the prescribed dose of the study intervention and to identify any Serious Adverse Events or Protocol Violations/Incidents that require expedited reporting to the Methods Centre. Study intervention is to be started within 2 hours of randomization. Duration of Data Collection Given the material affect on the study, these data are to be collected daily as close to REAL TIME as possible and as follows: Study Intervention: from randomization to 7 days post last successful grafting operation regardless of whether the patient is receiving enteral/parenteral nutrition, ventilation status or location of patient i.e. discharged to another ward. SAEs, Protocol Violations, etc: from randomization to 10 days post last successful grafting operation te: Duration of Study Intervention is from randomization to 7 days post last successful graft, or until ICU/burn unit discharge, or until 6 months from ICU admission, whatever comes first. Total # of Packets Prescribed per Day Record the total number of packets of study supplement prescribed per day at the top of each Daily Monitoring form in the spaces provided. te: The prescribed # of packets should remain the same for the duration of the study. Study Day # Record the Study Day number consecutively at the top of each column, starting at day 1. Reminder: Study Day 1 is the time from ICU admission until 23:59 that day, Study day 2 is the next 24 hrs period and so on. Date Enter the dates corresponding to the calendar day for the corresponding study day number. Time bolus given Record each time the Study medication was administered as a bolus. This is to be given at q 4 hr intervals if given via NG/feeding tube (unless weight is < 54 kg) or TID or QID if given po. If given q4h you should record 6 administrations per day. Depending on the timing of the study medication administration, you may have 5 or 7 administrations per day. Record each administration on the study day/date it was given. Refer to the Implementation Manual for more details on the Investigational Product Administration. # packets given Record the # packets given by the RN at each interval as documented in the medical chart. Route Percentage of packets received Protocol Violation Select the route by which the bolus was given at each interval, EN or PO. Divide the number of packets actually given by the number of packets prescribed per day (documented at the top of the page) to determine the percentage of packets received. Record the percentage in the space provided. A protocol violation with the delivery of the study intervention occurs when the patient received < 80% of the total prescribed daily dosage (expressed as # packets) over a 3 day average. Refer to the Dosing Weight Chart and the Protocol Violation Form for more details (Implementation Manual). In the event that the patient does not receive at least 80% prescribed # packets over a 3 day average, a Protocol Violation Form must be completed and faxed to CERU within 24 hours of becoming aware. SAE Record yes or no if an unexpected serious adverse event (SAE) occurred, or if an expected serious adverse event (SAE) related to the study medication occurred. In the event that a SAE (serious and unexpected OR serious expected and related) has occurred, a SAE form must be completed and faxed to CERU within 24 hours. Refer to the SAE section in the Implementation Manual for more details. Version: March 26,

17 Daily Monitoring Site Number - Enrollment Number Number of packets prescribed per day Page #: Study Day # dd/mmm/yyyy Day # Day # Day # Day # Day # Day # Day # 1-Time (hh mm) # packets given Route 2-Time (hh mm) # packets given Route 3-Time (hh mm) # packets given Route 4-Time (hh mm) # packets given Route 5-Time (hh mm) # packets given Route 6-Time (hh mm) # packets given Route X-Time (hh mm) # packets given Route Percentage of packets received today Protocol Violation SAE PO EN PO EN PO EN PO EN PO EN PO EN PO EN. % PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN PO EN. %. %. %. %. %. % Version: March 26,

18 Daily Organ Dysfunction Instructions General Instructions & Duration of Data Collection These data are collected for calculation of SOFA and organ dysfunction scores. These data are to be collected as follows while patient is mechanically ventilated: Daily from study Day 1-14 (first two weeks from ICU admission) Weekly from study Day 15 onwards until 10 days post last successful grafting or ICU/burn unit discharge or 6 months from ICU admission, whatever comes first. Study Day # Record the Study Day number consecutively at the top of each column, starting at day 1. Reminder: Study Day 1 is the time from ICU admission until 23:59 that day, Study day 2 is the next 24 hrs period and so on. Date Enter the dates corresponding to the calendar day for the corresponding study day number. Heart rate Core Temperature Record the highest heart rate observed during the study day. Select either C or F for how the temperature was recorded. Record the most aberrant core temperature from 37.0 C or 98.0 F observed during the study day. This refers to the temperature which deviates from 37.0 C or 98.0 F the most, not the highest temperature observed. For example, the following core temperatures were recorded on study day 1: 37.7ºC, 37.9ºC, 36.0ºC, 36.8ºC. A core temperature of 36.0ºC should be recorded in the CRF because it deviates the most from 37.0 C. To convert a non-core temperature to a core temperature: Oral temperature C = core temperature Axillary temperature C = core temperature. MAP Respiratory Rate Urine output (ml) Dialysis Vasopressors/ Inotropes Enter the lowest MAP observed during the study day. This value should only be recorded if the patient is NOT receiving any vasopressors (i.e. dopamine, dobutamine, norepinephrine, epinephrine, phenylephrine or vasopressin). If the patient receives vasopressors for any part of the study day then enter N/A. Enter the highest mechanical and/or spontaneous respiratory rate observed during the study day. Place a in the appropriate volume range for urine output for the study day. Indicate whether the patient received any type of dialysis at any point during the study day. Record the highest hourly dose infused for each of the following vasopressor/inotropes received during the study day. For the following use the units indicated: Dopamine (µg/kg/min) Dobutamine (µg/kg/min) Vasopressin (units/min) For the following indicate either µg/min or µg/kg/min by placing a in the appropriate box. repinephrine Epinephrine Phenylephrine Enter N/A in the row if no vasopressor/inotropes were administered that day. Version: March 26,

19 - Site Number Enrollment Number Daily Organ Dysfunction Page #: Study Day # Day # Day # Day # Day # Day # Day # Day # Date (dd/mmm/yyyy) Heart Rate (highest) Temperature (most aberrant) MAP (lowest) C F Respiratory Rate (highest) Urine output: < 200mls /day mls/day 500mls/day Dialysis today ( or ) Dopamine Highest dose µg/kg/min Dobutamine Highest dose µg/kg/min repinephrine µg/min Highest dose µg/kg/min Epinephrine µg/min Highest dose µg/kg/min Phenylephrine µg/min Highest dose µg/kg/min Vasopressin Highest dose units/min Version: March 26,

20 Daily Laboratory Instruction Duration of Data Collection These data are to be collected while patient is mechanically ventilated as follows: Daily from study Day 1-14 (first two weeks from ICU admission) Weekly from study Day 15 onwards until 10 days post last successful grafting or ICU/burn unit discharge or 6 months from ICU admission, whatever comes first. Study Day # Record the Study Day number consecutively at the top of each column, starting at day 1. Reminder: Study Day 1 is the time from ICU admission until 23:59 that day, Study day 2 is the next 24 hrs period and so on. Date PaO 2 /FiO 2 T-bilirubin highest Enter the dates corresponding to the calendar day for the corresponding study day number. Record the lowest PaO 2 /FiO 2 (PF ratio) observed on the study day. The PaO 2 and FiO 2 values should come from the same blood gas measurement. If no PF ratio record N/A Record the highest serum total bilirubin observed on the study day. Ammonia Record the highest blood ammonia level reported on the study day. Serum Creatinine lowest Record the highest serum creatinine observed on the study day. BS closest to 08:00 Record the blood sugar closest to 8am observed on the study day 6 hrs (i.e. from 02:00 to 14:00 hrs). Urea highest Record the highest serum urea observed on the study day. Albumin highest Record the highest serum albumin observed on the study day. Lactate highest Record the highest lactate level observed on the study day. If not available record n/a in the box. Platelets lowest Record the lowest serum platelets observed on the study day. WBC highest Record the highest white blood count observed on the study day. If there is only one value recorded for the 24 hr period then record the one value as the highest and lowest. WBC lowest Record the lowest white blood count observed on the study day. If there is only one value recorded for the 24 hr period then record the one value as the highest and lowest. For each requested result above, if there is no value available to record, indicate by entering N/A in the space provided. Version: March 26,

21 Site Number - Enrollment Number Daily Laboratory Page #: Study Day # Day # Day # Day # Day # Day # Day # Day # Date (dd/mm/yy) PaO2/FiO2 (lowest) T-bilirubin (highest) Ammonia (highest) Creatinine (highest) BS closest to 08:00 am Urea highest Albumin highest Lactate highest Platelets lowest WBC highest WBC lowest Version: March 26,

22 Daily Nutrition Instruction General Instructions Duration of Data Collection These data are collected to determine the adequacy of all types of nutrition (calories and protein received) These data are to be collected daily from Study Day 1 (ICU admission) until 10 days post last successful grafting or ICU/burn unit discharge or 6 months from ICU admission, whatever comes first. Study Day # Record the Study Day number consecutively at the top of each column, starting at day 1. Reminder: Study Day 1 is the time from ICU admission until 23:59 that day, Study day 2 is the next 24 hrs period and so on. Date Enter the dates corresponding to the calendar day for the corresponding study day number. Enteral Nutrition Today? Formula Formula Strength For each day, indicate whether the patient received enteral nutrition, or. If to Enteral Nutrition, using Appendix 3 Enteral Nutrition, choose the number that corresponds to the type of enteral formula received. You may record up to 3 different formulas used in a day. Record the first formula received in the spaces provided for Formula 1 and so on. If the formula given is not in Appendix 3, write the name of the formula in the space provided for If only one type of enteral formula is received, enter N/A in the 2nd and 3rd boxes. In the event that the patient receives more than 3 formulas in one day, select the 3 that provide the largest volumes. Record whether the formula strength is full strength (full), three quarter strength (3/4), half strength (1/2), one quarter strength (1/4), or any other strength for each formula in the space provided. Total kcals Total Protein Enteral Nutrition Today? (If ) Parenteral Nutrition today? Total Kcals Total Protein Oral feeding today? Total kcals & Protein Record the total calories (kilocalories) and protein from all the enteral nutrition formulas received in the study day. Include the calories and protein from any supplements. Do not include the calories from IV solutions (e.g. Dextrose). Do not record the calories from propofol (volume to be entered separately below). If to Enteral Nutrition, using the list below, indicate ALL the reason(s) the patient did not receive EN on the specified Study day by placing the number(s) in the box(es) provided: 1. NPO for endotracheal extubation or intubation or other bedside procedure 2. NPO for operating procedure 3. NPO for radiology procedure 4. High NG drainage 5. Increased abdominal girth, abdominal distension or pt. discomfort 6. Vomiting or emesis 7. Diarrhea 8. enteral access available / enteral access lost, displaced or malfunctioning 9. Inotropes, vasopressor requirement 10. Subject deemed too sick for enteral feeding 11. On oral feeds 12. Reason not known For each day, indicate whether the patient received parenteral nutrition, or. If yes, record the total calories (kilocalories) and grams of protein received from parenteral nutrition. Do not include the calories from IV solutions (e.g. Dextrose). Do not record the calories from propofol (volume to be entered separately below). Indicate whether the patient received any oral intake today, or This refers to the calorie (kilocalories) and protein intake from oral feeding only for at least the first week following the discontinuation of enteral feeding. Record the totals in the space provided. In the event that no calorie/protein intakes were kept, place a in the t Available box. Propofol today? Total mls Indicate whether the patient received a continuous infusion of Propofol for 6hrs, or. This is to be completed for each day regardless of whether the patient received enteral nutrition, parenteral nutrition or neither. Record the volume of propopfol received each day (mls) Version: March 26,

23 Daily Nutrition Study Day # DATE dd/mmm/yyyy Site Number - Enrollment Number Page #: EN today? Total kcals Reason(s) EN not received today Total protein gram Formula 1 # 1 - Strength Formula 2 Formula 3 # 2 - Strength # 3 - Strength PN today? Total kcals Total protein gram Oral feeding today? Total kcals Total protein gram t Available Propofol today for > 6 hours? Total ml Study Day # DATE dd/mmm/yyyy EN today? Total kcals Reason(s) EN not received today Total protein gram Formula 1 # 1 - Strength Formula 2 Formula 3 # 2 - Strength # 3 - Strength PN today? Total kcals Total protein gram Oral feeding today? Total kcals Total protein gram t Available Propofol today for > 6 hours? Total ml Study Day # DATE dd/mmm/yyyy EN today? Total kcals Reason(s) EN not received today Total protein gram Formula 1 # 1 - Strength Formula 2 Formula 3 # 2 - Strength # 3 - Strength PN today? Total kcals Total protein gram Oral feeding today? Total kcals Total protein gram t Available Propofol today for > 6 hours? Total ml Version: March 26,

24 Blood Sampling for Mechanistic Studies Instructions General Information Only complete this form if your site is participating in Optional Blood Sampling for Mechanistic Studies. These data are to be collected to determine the effect of the study intervention on mechanistic endpoints (i.e. lymphocyte function, heat shock proteins, inflammatory cytokines, etc) Duration of Data Collection Blood samples are to be drawn on the following days: Draw 1 (4 days post start of study intervention) 48 hrs Draw 2 (7 days post start of study intervention) 48 hrs Draw 3 (14 days post start of study intervention) 48 hrs Draw 4 (21 days post start of study intervention) 48 hrs Blood samples are to be drawn from the central line, wherever possible. If there is no central line, then blood should be drawn at the same time as routine blood work to prevent unnecessary blood draws. If there is no central line and there is no routine blood work scheduled for 4, 7, 14 or 21 days post start of study intervention (or the next day if weekend), do not draw blood. Blood samples must NOT be drawn within the period of 12 hrs after surgery or after a blood transfusion. It is ok to draw blood before surgery/transfusion. Refer to the Lab Manual for more details. Date and Time For each day of blood draw, complete the date the blood samples were taken in the format dd-mmm-yyyy and the time in the format of 24 hr clock. Blood samples should be drawn at the same time as regular morning blood draw, if possible. Specimen I.D. Record the Specimen ID in the spaces provided. The Specimen ID contains 9 numbers: the first digit represents the draw number, the next 4 digits are your site number, and the last 4 digits are the patient enrollment number (Refer to the Lab Manual for further details and instructions). If no blood samples taken, reason why Please document reason blood samples were not taken. Version: March 26,

25 Site Number Blood Sampling for Mechanistic Studies (Complete ONLY if participating in Optional Blood Sampling) - Enrollment Number Sample Details If no blood samples taken, explain why Draw # 1 Date Time D D M M M Y Y Y Y H H M M (24 hour clock) Specimen I.D. 1 Draw # Site Number 4 digit patient enrollment # Draw # 2 Date Time D D M M M Y Y Y Y H H M M (24 hour clock) Specimen I.D. 2 Draw # Site Number 4 digit patient enrollment # Draw # 3 Date Time D D M M M Y Y Y Y H H M M (24 hour clock) Specimen I.D. 3 Draw # Site Number 4 digit patient enrollment # Draw # 4 Date Time D D M M M Y Y Y H H M M (24 hour clock) Specimen I.D. 4 Draw # Site Number 4 digit patient enrollment # Version: March 26,

26 Burn Related Operative Procedures Instructions General Instructions These data are collected to determine the frequency and type of burn related operative procedures that the patient undergoes during the study. Duration of Data Collection Record all burn related operative procedures from Study Day 1 (ICU admit) to 10 days post last successful grafting or ICU/burn unit discharge or 6 months from ICU admission, whatever comes first. Study Day # Record the Study Day number consecutively at the top of each column, starting at day 1. Reminder: Study Day 1 is the time from ICU admission until 23:59 that day, Study day 2 is the next 24 hrs period and so on. Date Patient had a burn related procedure today or? Type of Operative Procedure Enter the dates corresponding to the calendar day for the corresponding study day number. Indicate or if the patient had undergone any burn related operative procedures. If Indicate from the taxonomy the type(s) of operation(s) performed that day. 1) Surgical excision (tangential or fascial) 2) Excision and temporary covering (xenograft, allograft and artificial skin) 3) Excison and autograft 4) Delayed autograft 5) Excision and primary closure/composite tissue transfer 6) Other specify example amputation Version: March 26,

27 Site Number - Enrollment Number Burn Related Operative Procedures Page #: Study Day # Day # Day # Day # Day # Day # Day # Day # dd/mmm/yyyy or? Type of operative procedure List all that apply Study Day # Day # Day # Day # Day # Day # Day # Day # dd/mmm/yyyy or? Type of operative procedure List all that apply Study Day # Day # Day # Day # Day # Day # Day # Day # dd/mmm/yyyy or? Type of operative procedure List all that apply Version: March 26,

28 Blood Products Instructions General Instructions Duration of Data Collection blood products received Date Blood Product These data are collected to capture all blood products the patient received. These data are to be collected on days that blood products were given for the following duration: Daily from Study Day 1 (ICU admit) until 10 days post last successful grafting or ICU/burn unit discharge or 6 months from ICU admission, whatever comes first. If no blood products were received during the study period then place a check in the box. Record the date that blood products (Platelets, Packed cells or Fresh Frozen Plasma) given. Indicate which of the following was received by placing a in the appropriate category: Platelets Packed Cells (PC) Fresh Frozen Plasma (FFP) Record the total volume of each of the blood products received by entering the number of units or mls in the corresponding spaces provided. If more than one type of blood product is received on the same day, record each type of blood product on a separate row. Version: March 26,

29 Site Number - Enrollment Number Blood Products Page #: NO BLOOD PRODUCTS RECEIVED Date Blood Product Volume Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Platelets PC FFP Units mls Version: March 26,

30 Concomitant Medication Instructions General Instructions Duration of Data Collection concomitant medications were given These data are collected to capture all relevant medications that the patient received that may have a material effect on the measured outcomes of the study. Record all concomitant medications started from Study day 1 (ICU admit) to 10 days after the last successful grafting or ICU/burn unit discharge or 6 months from ICU admission, whatever comes first. If no concomitant medications were given for the duration of the study, then place a in the box. Study Day # Record the Study Day number consecutively at the top of each column, starting at day 1. Reminder: Study Day 1 is the time from ICU admission until 23:59 that day, Study day 2 is the next 24 hrs period and so on. Date Insulin Enter the dates corresponding to the calendar day for the corresponding study day number. Indicate if insulin was given by placing a in the box or. If the information is t Available, indicate by placing a in the appropriate box. Record the total units received in the 24 hour period from all insulin IV, SC (subcutaneous) and bolus. If no insulin was given put a forward slash through the box. Opiates Indicate if any opiates were given by placing a in the box or. If the information is t Available, indicate by placing a in the appropriate box. Motility agents Indicate if any of the following motility agents were given by placing a in the box or : Maxeran Erythromycin Motilium Other If the information is t Available, indicate by placing a in the appropriate box. Oxandrolone Indicate if Oxandrolone was given by placing a in the box or. If the information is t Available, indicate by placing a in the appropriate box. Propanolol Indicate if Propanolol was given by placing a in the box or. If the information is t Available, indicate by placing a in the appropriate box. Version: March 26,

31 - Site Number Enrollment Number Concomitant medications given for the entire study Concomitant Medications Page #: Study Day # Day # Day # Day # Day # Day # Day # Day # DATE dd/mmm/yyyy Insulin given today? t Available t Available t Available t Available t Available t Available t Available Insulin total dose in units Opiates given today? t Available t Available t Available t Available t Available t Available t Available Motility agents given today? t Available t Available t Available t Available t Available t Available t Available Oxandrolone given today? t Available t Available t Available t Available t Available t Available t Available Propanolol given today? t Available t Available t Available t Available t Available t Available t Available Version: March 26,