Contents. Version 1.0: 01/02/2010 Protocol# ISRCTN Page 1 of 7
|
|
- Lawrence Carter
- 5 years ago
- Views:
Transcription
1
2 Contents 1. INTRODUCTION STUDY SYNOPSIS STUDY OBJECTIVES Primary Objective Secondary Objectives Assessment of Objectives Change the Primary Objective During the Conduct of the Study STUDY DESIGN General Design and Plan Sample Size Randomization and Blinding STUDY POPULATIONS Participant Characteristics Major Protocol Deviations Definition of Sub-Group Populations STATISTICAL ANALYSIS General Pooling of Sites Interim Analyses Time-Points For Analysis Methods for Handling Missing Data Statistical Analytical Issues EVALUATION OF DEMOGRAPHICS AND BASELINE CHARACTERISTICS Demographics and Baseline Characteristics EVALUATION OF TREATMENT COMPLIANCE AND EXPOSURE Compliance to Study Drug and Treatment EVALUATION OF PARAMETERS Analysis of Primary, Secondary, and Other Efficacy Endpoints Method for Analysis of Efficacy Endpoints EVALUATION OF SAFETY PARAMETERS Adverse Events... 7 Page 1 of 7
3 1. INTRODUCTION The outline statistical methods to be used for the analysis of trial data are included in the final trial Protocol. This analysis plan provides full details of the results to be presented. Shell data tables were created to provide an overview of the analysis to be conducted by the Data Monitoring and Ethics Committee (see Appendix 1). 2. STUDY SYNOPSIS A Randomised Placebo Controlled Trial Among Trauma Patients with Significant Haemorrhage of the Effects of Tranexamic Acid on Death and Transfusion Requirement (CRASH-2). 3. STUDY OBJECTIVES To quantify the effect on death, vascular events and transfusion requirements of the early administration of the antifibrinolytic agent tranexamic acid in patients with trauma and significant bleeding PRIMARY OBJECTIVE The primary outcome measure is death in hospital within four weeks of injury SECONDARY OBJECTIVES Secondary outcome measures are: Blood Products Blood products transfusion given Number of units of blood products transfused (including the total number of units of red cells, platelets, fresh frozen plasma and cryoprecipitate) Disability Death or dependency: this outcome will be measured using the five point Modified Oxford Handicap Scale. We will dichotomise the scale into independent (no symptoms; minor symptoms; some restriction in lifestyle but independent) and dependent (dependent, but not requiring constant attention; fully dependent; requiring attention day and night; death). Surgery Neurosurgery, chest operation, abdominal operation and pelvis operation. We will analyse all surgery combined and separately. Thromboembolic episodes Stroke, myocardial infarction, pulmonary embolism, clinical evidence of deep vein thrombosis. We will analyse thromboembolic episodes combined and separately. Page 2 of 7
4 Gastrointestinal bleeding Days in intensive care unit Causes of death will be described to assess whether deaths were due to bleeding, myocardial infarction, stroke, pulmonary embolism, vascular occlusion (bleeding or myocardial infarction or stroke or pulmonary embolism), multi-organ failure, head injury or other ASSESSMENT OF OBJECTIVES All outcome variables are recorded on the outcome form which is completed entirely from the hospital notes no extra tests are needed. The outcome form is completed at death, discharge or four weeks post randomisation, whichever occurs first CHANGE OF THE PRIMARY OBJECTIVE DURING THE CONDUCT OF THE STUDY There has not been any change in the primary outcome of the study. The following secondary outcomes were included: death or dependency, gastrointestinal bleeding, days in intensive care unit, and type of surgical intervention. 4. STUDY DESIGN 4.1 GENERAL DESIGN AND PLAN A randomised double blind placebo controlled trial. Adults with trauma who are within 8 hours of injury and have either significant haemorrhage, or who are considered to be at risk of significant haemorrhage, are eligible if the responsible doctor is for any reason substantially uncertain whether or not to use an antifibrinolytic agent. Numbered drug or placebo packs will be available in each participating emergency department. Randomisation will involve calling a 24-hour free-call randomisation service. The call should last only a minute or two and at the end of it the randomisation service will specify which numbered treatment pack to use. For hospitals where telephone randomisation is not feasible, randomisation will be by taking the next consecutively numbered treatment pack. No extra tests are required but a short form must be completed one month later or on discharge or on death (whichever occurs first). 4.2 SAMPLE SIZE Since even a 2% survival advantage for an intervention as simple as TXA would represent a worthwhile benefit, the main trial has been planned to be able to detect a benefit of this size. If the real mortality difference is in fact 20% versus 18%, then there is about an 85% chance that a trial involving 20,000 patients will achieve 2P<0.01 (and a 95% chance that it will achieve 2P<0.05). With such large numbers, even moderate effects on the numbers needing transfusion or on the mean number of Page 3 of 7
5 units transfused will be determined accurately, as will any substantial effects on nonfatal vascular events (haemorrhagic or occlusive). 4.3 RANDOMISATION AND BLINDING Patients are randomised in one of two ways: Hospitals with reliable telephone access, where the recruiting doctors are able to provide baseline data in English, will use the central telephone randomisation service provided by the Clinical Trial Service Unit (CTSU) in Oxford. During the call, which will last 2-3 minutes, baseline data are collected and recorded on the central computer. To achieve a reasonable balance on the key prognostic factors, the allocation uses a minimisation algorithm balancing for sex, age (16-24 years, years, 35 years and older), hours since injury (1 hour or less, 1-3 hours, over 3 hours), type of injury (blunt or penetrating), Glasgow Coma Scale (3, 4-5, 6-8, 9-12, 13-15), Systolic Blood Pressure (>89, 76-89, 50-75, 1-49, 0), Respiratory Rate (>29, 10-29, 6-9, 1-5, 0), Central Capillary Refill Time (2 or less, 3-4, 5 or more) and country, bearing in mind what packs remain at that hospital. The allocated treatment pack number will be given and recorded on the trial entry form. Hospitals in which the doctors feel that central randomisation is not feasible will use a local pack system. At such hospitals, baseline information will be collected on the trial entry form and the next consecutively numbered treatment pack taken from a box of eight packs (with a random allocation sequence based on a block size of eight, also generated by CTSU). Once the pack number is recorded, the patient is included in the trial whether or not the pack was opened or the allocated treatment started Blinding Blinding is achieved through the use of matching placebo. The blinding process is described in Appendix STUDY POPULATIONS 5.1 PARTICIPANT CHARACTERISTICS A trial profile of participants will be presented as per the CONSORT recommendations (figure 1). The table of baseline characteristics will be as per Table 4 in DMEC shell tables but excluding the components of the GCS. 5.2 DEFINITION OF POPULATIONS FOR ANALYSIS The analyses will be on an intention-to-treat basis. All patients will be analysed on the basis of the group to which they were randomised, irrespective of whether the patients in the intervention group actually received the intervention. 5.3 MAJOR PROTOCOL DEVIATIONS These will be described in the results section. Page 4 of 7
6 5.4 DEFINITION OF SUB-GROUP POPULATIONS Analysis of the primary outcome will be stratified on: hours from injury to randomisation and the initiation of treatment (less than one hour, one to three hours, more than three hours) severity of haemorrhage as assessed by systolic blood pressure ( 75, 76-89, >89 mmhg) Glasgow Coma Scale (severe [GCS 3-8], moderate [GCS 9-12], mild [GCS 13-15]) type of injury (blunt/blunt & penetrating, or penetrating only) Subsequent analyses will include subgroup analyses according to baseline risk of mortality. We will develop a prognostic model including all the baseline variables (age, sex, systolic blood pressure, heart rate, respiratory rate, Glasgow Coma Score, number of hours since injury, central capillary refill time and type of injury). This model will be derived only from the control group. We will categorise the patients according to tertiles of risk and we will report the relative and absolute measures of effect for each category. 6. STATISTICAL ANALYSIS 6.1 GENERAL For each binary outcome we will report relative risks with 95% confidence intervals and give a two-sided p-value for statistical significance. For analysis of the prespecified subgroups (primary outcome only) we will report relative risks with 99% confidence intervals with two-sided p-value. 6.2 POOLING OF SITES The data will be pooled across all participating sites. 6.3 INTERIM ANALYSES Interim analyses were conducted by the independent DMEC as per the DMEC SOP. 6.4 TIME-POINTS FOR ANALYSIS There will be one analysis at the end of the trial after the database has been locked. 6.5 METHODS FOR HANDLING MISSING DATA A complete case analysis will be conducted (i.e. only including cases for which the relevant outcome data are available). There will be no imputation for missing data. Page 5 of 7
7 6.6 STATISTICAL ANALYTICAL ISSUES Adjustments for covariate There will be no covariate adjustment in the primary analysis Multiple Comparisons There will be no adjustment for multiple comparisons. We will report 99% confidence intervals for subgroup analyses of the primary outcome Examination of Subgroups We will report relative risks with 99% confidence intervals for the primary outcome by the following subgroups: hours from injury severity of haemorrhage systolic blood pressure ( 75, 76-89, >89 mmhg) Glasgow Coma Scale (severe, moderate, mild) type of injury (blunt, blunt & penetrating, or penetrating only) We will conduct a test of homogeneity of effects across the subgroups and report a p- value. Unless there is strong evidence against the null hypothesis of homogeneity of effects (i.e. p<0.001) the overall relative risk will be considered as the most reliable guide to the approximate relative risks in all subgroups. 7. EVALUATION OF DEMOGRAPHICS AND BASELINE CHARACTERISTICS 7.1 DEMOGRAPHICS AND BASELINE CHARACTERISTICS As outlined above, a trial profile will be presented as per the CONSORT recommendations (figure 1). The baseline characteristics will be presented according to treatment (table 1). 8. EVALUATION OF TREATMENT COMPLIANCE AND EXPOSURE 8.1 COMPLIANCE TO STUDY DRUG AND TREATMENT Compliance with study treatment will be defined as: Received allocated intervention (loading dose) Known not to have received allocated intervention (loading dose) Unknown whether received allocated intervention (loading dose) Continued allocated intervention (maintenance dose) Known not to have continued allocated intervention (maintenance dose) Unknown whether continued allocated intervention (maintenance dose) This will be reported in figure 1. Page 6 of 7
8 9. EVALUATION OF PARAMETERS 9.1 ANALYSIS OF PRIMARY, SECONDARY AND OTHER EFFICACY ENDPOINTS See section 6 above. 9.2 METHOD FOR ANALYSIS OF EFFICACY ENDPOINTS Binary Data For each binary outcome we will report relative risks with 95% confidence intervals and give a two-sided p-value for statistical significance. For analysis of the prespecified subgroups (primary outcome only) we will report relative risks with 99% confidence intervals with two-sided p-value Count Data Means and standard deviations will be estimated for count outcomes. We will report the two-sided p-value for statistical significance of the difference in means of logarithms of count outcomes Time-to-Event Data There will be no analysis of time to event data Ordinal Scales and Non-Ordered Scales Data For the analysis of the patients condition at discharge, the five point scale will be dichotomised into independent (no symptoms, minor symptoms, and some restriction in lifestyle but independent) and dependent (including death) categories. 10. EVALUATION OF SAFETY PARAMETERS 10.1 ADVERSE EVENTS Numbers and type will be described using MedDRA codes (Version 12.1). Page 7 of 7
9 FIGURE 1 CONSORT FLOW OF PATIENTS Randomization (n=) Allocated to TXA (n=) Received allocated intervention (n=) Known not to have received allocated intervention (n=) Unknown whether received allocated intervention (n=) Continued allocated intervention (n=) Known not to have continued allocated intervention (n=) Unknown if allocated intervention continued (n=) Allocation (loading dose) Allocation (maintenance dose) Allocated to placebo (n=) Received allocated intervention (n=) Known not to have received allocated intervention (n=) Unknown whether received allocated intervention (n=) Continued allocated intervention (n=) Known not to have continued allocated intervention (n=) Unknown if allocated intervention continued (n=) No follow up (n=) Follow up No follow up (n=) Analysed (n=) Analysis Analysed (n=) Version 1.0 FINAL Page 1 SAP Appendix 1: Shell tables for analysis
10 TABLE 1 BASELINE DATA ALL PATIENTS RANDOMIZED Percentages are of group total unless specified Patients randomized as of <Date> Gender 2 Age 2 Hours since injury 2 Type of injury 2 Systolic BP (mmhg) 2 Respiratory rate (per min) 2 Male Female Mean age in years (SD) <25 years years years 45 years <1 hour 1 3 hours >3 hours Blunt Penetrating 90 mmhg SBP mmhg SBP 75 mmhg SBP <6 4 Central capillary refill time (secs) 2 2 or less 3 to 4 5 or more Heart rate (per min) 2 > <77 Glasgow Coma Score 2 Median [IQR] Severe (GCS 3 8) Moderate (GCS 9 12) Mild (GCS 13 15) Blunt/ Blunt & penetrating TXA Placebo Version 1.0 FINAL Page 2 SAP Appendix 1: Shell tables for analysis
11 TABLE 2. DEATH WITHIN 4 WEEKS ALL PATIENTS RANDOMIZED TXA Placebo RR (95% CI) p value All patients Pre specified subgroups RR (99% CI) p value (i) Severity of haemorrhage 90 mmhg SBP mmhg SBP 75 mmhg SBP (ii) Time since injury <1 hour 1 3 hours >3 hours (iii) Glasgow Coma Scale Severe (GCS 3 8) Moderate (GCS 9 12) Mild (GCS 13 15) (iv) Type of injury Blunt* Penetrating only * Blunt/ Blunt & penetrating Analysis will include p value from test of homogeneity of effects between subgroups TABLE 3 BLOOD PRODUCTS TRANSFUSION GIVEN TXA Placebo RR (95% CI) p value All patients All types of blood products (including red cells, fresh frozen plasma, platelets and cryoprecipitate) TABLE 4 DISTRIBUTION OF NUMBER OF BLOOD UNITS TXA Placebo Mean difference (95% CI) p value Mean units transfused [SD] Analysis will use logarithmic transformation of number of units transfused TABLE 5. DEATH OR DEPENDENCY AT 4 WEEKS, DISCHARGE, OR TRANSFER TXA Placebo RR (95% CI) p value All patients Version 1.0 FINAL Page 3 SAP Appendix 1: Shell tables for analysis
12 TABLE 6 MANAGEMENT AND COMPLICATIONS All surgery Thromboembolic episodes Gastrointestinal bleeding NS operation Chest operation Abdominal operation Pelvis operation Pulmonary embolism Deep vein thrombosis Stroke Myocardial infarction TXA Placebo RR (95% CI) p value Days in intensive care unit Mean days in ICU [SD] Analysis will use logarithmic transformation of number of days in ICU Mean difference (95% CI) p value TABLE 7. CAUSE OF DEATH Bleeding Vascular occlusion Multi organ failure Head injury Other Myocardial infarction Stroke Pulmonary embolism TXA Placebo RR (95% CI) p value Notes 1. All analyses include all patients randomized, on an intention to treat basis 2. Groups are pre specified randomization strata 3. Includes patients for whom Systolic BP was not known 4. Includes patients for whom respiratory rate was not known 5. Denominators are of patients with management data received; numerators are number of patients noncompliant 6. Denominators are of patients with information on dose received * indicates z > 3 Version 1.0 FINAL Page 4 SAP Appendix 1: Shell tables for analysis
13
DATA DICTIONARY FOR THE DATA SET CRASH-2 DATA FOR SUNGAI BULOH
A LARGE RANDOMISED PLACEBO CONTROLLED TRIAL AMONG TRAUMA PATIENTS WITH OR AT RISK OF SIGNIFICANT HAEMORRHAGE, OF THE EFFECTS OF ANTIFIBRINOLYTIC TREATMENT ON DEATH AND TRANSFUSION REQUIREMENT DATA DICTIONARY
Antifibrinolytic drugs for acute traumatic injury(review)
Cochrane Database of Systematic Reviews Antifibrinolytic drugs for acute traumatic injury(review) KerK,RobertsI,ShakurH,CoatsTJ KerK,RobertsI,ShakurH,CoatsTJ. Antifibrinolytic drugs for acute traumatic
Transfusion Requirements and Management in Trauma RACHEL JACK
Transfusion Requirements and Management in Trauma RACHEL JACK Overview Haemostatic resuscitation Massive Transfusion Protocol Overview of NBA research guidelines Haemostatic resuscitation Permissive hypotension
Gastrointestinal haemorrhage
Gastrointestinal haemorrhage A common emergency Important cause of mortality and morbidity Case fatality is high (10 20% in the UK) Rockall TA et al. BMJ, 1995. 311(6999): p. 222-6. Williams JG et al.
Blood Pressure Reduction Among Acute Stroke Patients A Randomized Controlled Clinical Trial
Blood Pressure Reduction Among Acute Stroke Patients A Randomized Controlled Clinical Trial Jiang He, Yonghong Zhang, Tan Xu, Weijun Tong, Shaoyan Zhang, Chung-Shiuan Chen, Qi Zhao, Jing Chen for CATIS
Review of the TICH-2 Trial
Review of the TICH-2 Trial Mikaela Hofer, PharmD PGY-1 Pharmacy Resident Pharmacy Grand Rounds September 18, 2018 2018 MFMER slide-1 Objectives Review the pharmacologic options to limit hematoma expansion
Reprint of Original Article
Reprint of Original Article Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled
Centocor Ortho Biotech Services, LLC
SYNOPSIS Issue Date: 17 June 2009 Name of Sponsor/Company Name of Finished Product PROCRIT Name of Active Ingredient(s) Protocol No.: PR04-15-001 Centocor Ortho Biotech Services, LLC Epoetin alfa Title
BACKGROUND AND SCIENTIFIC RATIONALE. Protocol Code: ISRCTN V 1.0 date 30 Jan 2012
BACKGROUND AND SCIENTIFIC RATIONALE Protocol Code: ISRCTN15088122 V 1.0 date 30 Jan 2012 Traumatic Brain Injury 10 million killed or hospitalised every year 90% in low and middle income countries Mostly
FVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial. Joseph P. Broderick, MD James Grotta, MD Jordan Elm, PhD
FVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial Joseph P. Broderick, MD James Grotta, MD Jordan Elm, PhD Background Intracerebral hemorrhage (ICH) accounts for more than
A Very Early Rehabilitation Trial (AVERT): What we know, what we think and what s to come
A Very Early Rehabilitation Trial (AVERT): What we know, what we think and what s to come The AVERT Trial Collaboration group Joshua Kwant, Blinded Assessor 17 th May 2016 NIMAST Nothing to disclose Disclosure
TITLE: Tranexamic Acid for the Management of Bleeding: A Review of the Clinical Effectiveness and Guidelines
TITLE: Tranexamic Acid for the Management of Bleeding: A Review of the Clinical Effectiveness and Guidelines DATE: 24 June 2013 CONTEXT AND POLICY ISSUES Bleeding or hemorrhage indicates a blood loss from
CHL 5225 H Advanced Statistical Methods for Clinical Trials. CHL 5225 H The Language of Clinical Trials
CHL 5225 H Advanced Statistical Methods for Clinical Trials Two sources for course material 1. Electronic blackboard required readings 2. www.andywillan.com/chl5225h code of conduct course outline schedule
Deep vein thrombosis and its prevention in critically ill adults Attia J, Ray J G, Cook D J, Douketis J, Ginsberg J S, Geerts W H
Deep vein thrombosis and its prevention in critically ill adults Attia J, Ray J G, Cook D J, Douketis J, Ginsberg J S, Geerts W H Authors' objectives To systematically review the incidence of deep vein
RATIONALE AND OVERVIEW
Tranexamic acid for the treatment of significant traumatic brain injury: an international randomised, double blind placebo controlled trial RATIONALE AND OVERVIEW Protocol Code: ISRCTN15088122 V 1.1 date
Journal Club. 1. Develop a PICO (Population, Intervention, Comparison, Outcome) question for this study
Journal Club Articles for Discussion Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-pa Stroke Study Group. N Engl J Med. 1995 Dec
Online Appendix (JACC )
Beta blockers in Heart Failure Collaborative Group Online Appendix (JACC013117-0413) Heart rate, heart rhythm and prognostic effect of beta-blockers in heart failure: individual-patient data meta-analysis
Critical Review Form Therapy
Critical Review Form Therapy Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion Lancet 1993; 341:501-511 Objective: To determine
What can we learn from the AVERT trial (so far)?
South West Stroke Network Event, 29 th April, 2015 What can we learn from the AVERT trial (so far)? Peter Langhorne, Professor of stroke care, Glasgow University Disclosure PL was AVERT investigator and
University of Bristol - Explore Bristol Research
Rogers, C., Capoun, R., Scott, L., Taylor, J., Angelini, G., Narayan, P.,... Ascione, R. (2017). Shortening cardioplegic arrest time in patients undergoing combined coronary and valve surgery: results
Statistical Analysis Plan
Effectiveness of nutritional supplementation (RUTF and multi micronutrient) in preventing malnutrition in children 6-59 months with infection (malaria, pneumonia, diarrhoea), a randomized controlled trial
HORMONE REPLACEMENT THERAPY
TRIALS OF HR RUTH (Barrett- Connor et al 29 ) JULY 2006 (Country) mean ± sd, range International trial 67.5 an Placebo component in 67.5 ± 6.7 women with Raloxifene or multiple 67.5 ± 6.6 risk factors
Pre-hospital Administration of Blood Products (PHBP) and Tranexamic acid (TXA): Is the Jury Still Out?
Pre-hospital Administration of Blood Products (PHBP) and Tranexamic acid (TXA): Is the Jury Still Out? Jessica K. Reynolds, MD Assistant Professor of Surgery University of Kentucky, Department of Trauma
An introduction to Quality by Design. Dr Martin Landray University of Oxford
An introduction to Quality by Design Dr Martin Landray University of Oxford Criteria for a good trial Ask an IMPORTANT question Answer it RELIABLY Quality Quality is the absence of errors that matter to
PFIZER INC. THERAPEUTIC AREA AND FDA APPROVED INDICATIONS: See USPI.
PFIZER INC. These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert. For publications based on this study, see associated bibliography.
London School of Hygiene and Tropical Medicine, Keppel Street, London, UK 2
CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury a nested, randomised, placebo-controlled
Supplementary Online Content
Supplementary Online Content Cooper DJ, Nichol A, Bailey M, et al. Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury: the POLAR
CRASH ing Trauma Patients: The CRASH trials. Tim Coats Professor of Emergency Medicine University of Leicester, UK
CRASH ing Trauma Patients: The CRASH trials Tim Coats Professor of Emergency Medicine University of Leicester, UK www.le.ac.uk/emag I DO NOT have an affiliation (financial or otherwise) with a pharmaceutical,
Session 7: The Sliding Dichotomy 7.1 Background 7.2 Principles 7.3 Hypothetical example 7.4 Implementation 7.5 Example: CRASH Trial
Session 7: The Sliding Dichotomy 7.1 Background 7.2 Principles 7.3 Hypothetical example 7.4 Implementation 7.5 Example: CRASH Trial Session 7 1 7.1 The Sliding Dichotomy: Background The sliding dichotomy
WATCHMAN PROTECT AF Study Rev. 6
WATCHMAN PROTECT AF Study Rev. 6 Protocol Synopsis Title WATCHMAN Left Atrial Appendage System for Embolic PROTECTion in Patients with Atrial Fibrillation (PROTECT AF) Sponsor Atritech/Boston Scientific
FOCUS: Fluoxetine Or Control Under Supervision Results. Martin Dennis on behalf of the FOCUS collaborators
FOCUS: Fluoxetine Or Control Under Supervision Results Martin Dennis on behalf of the FOCUS collaborators Background Pre clinical and imaging studies had suggested benefits from fluoxetine (and other SSRIs)
Statistical Analysis Plan
The BALANCED Anaesthesia Study A prospective, randomised clinical trial of two levels of anaesthetic depth on patient outcome after major surgery Protocol Amendment Date: November 2012 Statistical Analysis
Tranexamic acid for intracerebral haemorrhage: (TICH-2) trial. Nikola Sprigg On behalf of the TICH-2 investigators
Tranexamic acid for intracerebral haemorrhage: (TICH-2) trial Nikola Sprigg On behalf of the TICH-2 investigators Disclosures TICH-2 funded by National Institute of Health Research Health Technology Assessment
ARTEMIS. ARixtra (fondaparinux) for ThromboEmbolism prevention in. a Medical Indications Study. NV Organon Protocol 63129
ARTEMIS ARixtra (fondaparinux) for ThromboEmbolism prevention in NV Organon Protocol 63129 a Medical Indications Study Objective To demonstrate efficacy and to assess safety of oncedaily subcutaneous (SC)
ASCEND Randomized placebo-controlled trial of aspirin 100 mg daily in 15,480 patients with diabetes and no baseline cardiovascular disease
ASCEND Randomized placebo-controlled trial of aspirin 100 mg daily in 15,480 patients with diabetes and no baseline cardiovascular disease Jane Armitage and Louise Bowman on behalf of the ASCEND Study
the bleeding won t stop? Liane Manz RN, BScN, CNCC(c) Royal Alexandra Hospital
What do you do when the bleeding won t stop? Teddie Tanguay RN, MN, NP, CNCC(c) Teddie Tanguay RN, MN, NP, CNCC(c) Liane Manz RN, BScN, CNCC(c) Royal Alexandra Hospital Outline Case study Normal coagulation
Supplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: The National Heart, Lung, and Blood Institute Acute Respiratory
Addition of clopidogrel to aspirin in patients with acute myocardial infarction: randomised placebo-controlled trial
Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative
Shock and Resuscitation: Part II. Patrick M Reilly MD FACS Professor of Surgery
Shock and Resuscitation: Part II Patrick M Reilly MD FACS Professor of Surgery Trauma Patient 1823 / 18 Police Dropoff Torso GSW Lower Midline / Right Buttock Shock This Monday Trauma Patient 1823 / 18
Clinically Important Outcomes in ICU research
Clinically Important Outcomes in ICU research Michaël Chassé, MD, PhD, FRCPC Intensivist, Centre Hospitalier de l Université de Montréal Clinical Assistant Professor, Department of Medicine, University
A factorial randomized trial of blood pressure lowering and intensive glucose control in 11,140 patients with type 2 diabetes
A factorial randomized trial of blood pressure lowering and intensive glucose control in 11,140 patients with type 2 diabetes Hypotheses: Among individuals with type 2 diabetes, the risks of major microvascular
Supplemental Appendix. 1. Protocol Definition of Sustained Virologic Response. A patient has a sustained virologic response if:
Supplemental Appendix 1. Protocol Definition of Sustained Virologic Response A patient has a sustained virologic response if: 1. The patient is a responder at the end of treatment and all subsequent planned
Transfusion for the sickest ICU patients: Are there unanswered questions?
Transfusion for the sickest ICU patients: Are there unanswered questions? Tim Walsh Professor of Critical Care Edinburgh University None Conflict of Interest Guidelines on the management of anaemia and
Technology appraisal guidance Published: 15 March 2012 nice.org.uk/guidance/ta249
Dabigatran an etexilate for the preventionention of stroke and systemic embolism in atrial fibrillation Technology appraisal guidance Published: 15 March 2012 nice.org.uk/guidance/ta249 NICE 2012. All
Antiplatelet Therapy in Primary CVD Prevention and Stable Coronary Artery Disease. Καρακώστας Γεώργιος Διευθυντής Καρδιολογικής Κλινικής, Γ.Ν.
Antiplatelet Therapy in Primary CVD Prevention and Stable Coronary Artery Disease Καρακώστας Γεώργιος Διευθυντής Καρδιολογικής Κλινικής, Γ.Ν.Κιλκίς Primary CVD Prevention A co-ordinated set of actions,
What to do with missing data in clinical registry analysis?
Melbourne 2011; Registry Special Interest Group What to do with missing data in clinical registry analysis? Rory Wolfe Acknowledgements: James Carpenter, Gerard O Reilly Department of Epidemiology & Preventive
Data Analysis Plan for assessing clinical efficacy and safety of ER niacin/laropiprant in the HPS2-THRIVE trial
Data Analysis Plan for assessing clinical efficacy and safety of ER niacin/laropiprant in the HPS2-THRIVE trial 1 Background This Data Analysis Plan describes the strategy, rationale and statistical methods
EDMS #4298 Version 1.0
Randomized EValuation of the Effects of Anacetrapib through Lipid-modification (HPS3/TIMI55 REVEAL) Data Analysis Plan Version 1.0 1 Table of Contents 1 VERSION HISTORY... 2 2 INTRODUCTION... 3 2.1 BACKGROUND...
Primary Endpoint The primary endpoint is overall survival, measured as the time in weeks from randomization to date of death due to any cause.
CASE STUDY Randomized, Double-Blind, Phase III Trial of NES-822 plus AMO-1002 vs. AMO-1002 alone as first-line therapy in patients with advanced pancreatic cancer This is a multicenter, randomized Phase
What is the risk of venous thromboembolism (VTE) in patients treated by an Outpatient Parenteral Antimicrobial Therapy (OPAT) Service?
What is the risk of venous thromboembolism (VTE) in patients treated by an Outpatient Parenteral Antimicrobial Therapy (OPAT) Service? David A. Barr; Sharon Irvine; Neil D. Ritchie; Jay McCutcheon; R.
PATCH Analysis Plan v1.2.doc Prophylactic Antibiotics for the Treatment of Cellulitis at Home: PATCH Analysis Plan for PATCH I and PATCH II Authors: Angela Crook, Andrew Nunn, James Mason and Kim Thomas,
Endovascular or open repair for ruptured abdominal aortic aneurysm: 30-day outcomes from
Web supplement for Endovascular or open repair for ruptured abdominal aortic aneurysm: 30-day outcomes from the IMPROVE trial IMPROVE trial investigators Containing: page Risk differences for mortality
CONSORT 2010 checklist of information to include when reporting a randomised trial*
CONSORT 2010 checklist of information to include when reporting a randomised trial* Section/Topic Title and abstract Introduction Background and objectives Item No Checklist item 1a Identification as a
Disclosures (2013 to the present)
What level and types of CV safety data acquisition should be considered to sufficiently characterize a drug s benefit/risk assessment by the end of Phase 3 development? Cardiac Safety Research Consortium
2.0 Synopsis. Adalimumab R&D/04/118. (For National Authority Use Only) Referring to Part of Dossier: Volume:
2.0 Synopsis Abbott Laboratories Name of Study Drug: Adalimumab Name of Active Ingredient: Adalimumab Title of Study: Individual Study Table Referring to Part of Dossier: Volume: Page: (For National Authority
ADVANCE post trial ObservatioNal Study
Hot Topics in Diabetes 50 th EASD, Vienna 2014 ADVANCE post trial ObservatioNal Study Sophia Zoungas The George Institute The University of Sydney Rationale and Study Design Sophia Zoungas The George Institute
Randomized comparison of single versus double mammary coronary artery bypass grafting: 5 year outcomes of the Arterial Revascularization Trial
Randomized comparison of single versus double mammary coronary artery bypass grafting: 5 year outcomes of the Arterial Revascularization Trial Embargoed until 10:45 a.m. CT, Monday, Nov. 14, 2016 David
ACUTE KIDNEY INJURY (AKI) ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) ADVANCED DIRECTIVE LIMITING CARE...91 AGE...9 AGE UNITS...
ACUTE KIDNEY INJURY (AKI)...122 ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)...124 ADVANCED DIRECTIVE LIMITING CARE...91 AGE...9 AGE UNITS...10 AIRBAG DEPLOYMENT...30 AIS PREDOT CODE...118 AIS SEVERITY...119
This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.
abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the
Occurrence of Bleeding and Thrombosis during Antiplatelet therapy In Non-cardiac surgery. A prospective observational study.
Occurrence of Bleeding and Thrombosis during Antiplatelet therapy In Non-cardiac surgery A prospective observational study OBTAIN Study Statistical Analysis Plan of Final Analysis Final Version: V1.1 from
Thicker than Water. Alisa McQueen MD, FAAP, FACEP Associate Professor of Pediatrics The University of Chicago
Thicker than Water Alisa McQueen MD, FAAP, FACEP Associate Professor of Pediatrics The University of Chicago I have no relevant financial relationships to disclose. Who is bleeding? How much and what kind
Supplementary appendix
Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Blum CA, Nigro N, Briel M, et al. Adjunct prednisone
4. Which survey program does your facility use to get your program designated by the state?
TRAUMA SURVEY Please complete one survey for each TCD designation you have in your facility. There would be a maximum of three surveys completed if your facility was designated as a trauma, stroke and
DVT PROPHYLAXIS IN HOSPITALIZED MEDICAL PATIENTS SAURABH MAJI SR (PULMONARY,MEDICINE)
DVT PROPHYLAXIS IN HOSPITALIZED MEDICAL PATIENTS SAURABH MAJI SR (PULMONARY,MEDICINE) Introduction VTE (DVT/PE) is an important complication in hospitalized patients Hospitalization for acute medical illness
Clinical Trial Synopsis TL-OPI-525, NCT#
Clinical Trial Synopsis, NCT#00762736 Title of Study: A Phase II, Double-Blind, Randomized, Placebo-Controlled, Proof-of-Concept Study of the Efficacy, Safety, and Tolerability of Pioglitazone HCl (ACTOS
CHOLESTEROL-LOWERING THERAPHY
CHOLESTEROL-LOWERING THERAPHY TRIALS NUMBER OF PARTICIPANTS NUMBER OF WOMEN PERCENTAGE OF WOMEN MEAN AGE MEAN - (YEARS) TRIALS WITH ANALYSIS BY GENDER N, (%) 50,194 15,036 30.0% 60.8 3.2 1/ 6 (16.7%) HR
Ultrasound-enhanced, catheter-directed thrombolysis for pulmonary embolism
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE Interventional procedure consultation document Ultrasound-enhanced, catheter-directed thrombolysis for pulmonary embolism A pulmonary embolism (PE) is
INTERVAL trial Statistical analysis plan for principal paper
INTERVAL trial Statistical analysis plan for principal paper 8 January 2016, final agreed version Compiled by Simon Thompson, on behalf of the INTERVAL Trial Steering Committee 1. Aim The purpose of this
SYNOPSIS. Study center(s) This study was conducted in the United States (128 centers).
Drug product: Drug substance(s): Document No.: Edition No.: Study code: Date: SYMBICORT pmdi 160/4.5 µg Budesonide/formoterol SD-039-0725 17 February 2005 SYNOPSIS A Twelve-Week, Randomized, Double-blind,
GSK Medicine: Study Number: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
HERMES Time and Workflow Primary Paper. Statistical Analysis Plan
HERMES Time and Workflow Primary Paper Statistical Analysis Plan I. Study Aims This is a post-hoc analysis of the pooled HERMES dataset, with the following specific aims: A) To characterize the time period
SYNOPSIS. Publications No publications at the time of writing this report.
Drug product: TOPROL-XL Drug substance(s): Metoprolol succinate Study code: D4020C00033 (307A) Date: 8 February 2006 SYNOPSIS Dose Ranging, Safety and Tolerability of TOPROL-XL (metoprolol succinate) Extended-release
British Society of Gastroenterology. St. Elsewhere's Hospital. National Comparative Audit of Blood Transfusion
British Society of Gastroenterology UK Com parat ive Audit of Upper Gast roint est inal Bleeding and t he Use of Blood Transfusion Extract December 2007 St. Elsewhere's Hospital National Comparative Audit
Recombinant Factor VIIa for Intracerebral Hemorrhage
Recombinant Factor VIIa for Intracerebral Hemorrhage January 24, 2006 Justin Lee Pharmacy Resident University Health Network Outline 1. Introduction to patient case 2. Overview of intracerebral hemorrhage
Bias and confounding special issues. Outline for evaluation of bias
EPIDEMIOLOGI BIAS special issues and discussion of paper April 2009 Søren Friis Institut for Epidemiologisk Kræftforskning Kræftens Bekæmpelse AGENDA Bias and confounding special issues Confounding by
Critical Appraisal. Dave Abbott Senior Medicines Information Pharmacist
Critical Appraisal Dave Abbott Senior Medicines Information Pharmacist Aims Identify key components of clinical trial design and apply these to a critical appraisal of the literature Be able to work out
Experiences with interim trial monitoring, particularly with early stopped trials
Experiences with interim trial monitoring, particularly with early stopped trials 1 Robert J Glynn, ScD Divisions of Preventive Medicine and Pharmacoepidemiology & Pharmacoeconomics, Brigham & Women s
Efficacy of beta-blockers in heart failure patients with atrial fibrillation: An individual patient data meta-analysis
Efficacy of beta-blockers in heart failure patients with atrial fibrillation: An individual patient data meta-analysis Dipak Kotecha, MD PhD on behalf of the Selection of slides presented at the European
Venous Thromboembolism Prophylaxis
Approved by: Venous Thromboembolism Prophylaxis Vice President and Chief Medical Officer; and Vice President and Chief Operating Officer Corporate Policy & Procedures Manual Number: Date Approved January
ESM1 for Glucose, blood pressure and cholesterol levels and their relationships to clinical outcomes in type 2 diabetes: a retrospective cohort study
ESM1 for Glucose, blood pressure and cholesterol levels and their relationships to clinical outcomes in type 2 diabetes: a retrospective cohort study Statistical modelling details We used Cox proportional-hazards
CADTH CANADIAN DRUG EXPERT COMMITTEE FINAL RECOMMENDATION
CADTH CANADIAN DRUG EXPERT COMMITTEE FINAL RECOMMENDATION Edoxaban (Lixiana SERVIER Canada Inc.) Indication: Prevention of Stroke and Systemic Embolic Events in Patients With Nonvalvular Atrial Fibrillation
Cover Page. The handle holds various files of this Leiden University dissertation.
Cover Page The handle http://hdl.handle.net/188/20915 holds various files of this Leiden University dissertation. Author: Flinterman, Linda Elisabeth Title: Risk factors for a first and recurrent venous
Study No.: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives: Co-Primary Outcomes/Efficacy Variables:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
Online Supplementary Data. Country Number of centers Number of patients randomized
A Randomized, Double-Blind, -Controlled, Phase-2B Study to Evaluate the Safety and Efficacy of Recombinant Human Soluble Thrombomodulin, ART-123, in Patients with Sepsis and Suspected Disseminated Intravascular
(n=6279). Continuous variables are reported as mean with 95% confidence interval and T1 T2 T3. Number of subjects
Table 1. Distribution of baseline characteristics across tertiles of OPG adjusted for age and sex (n=6279). Continuous variables are reported as mean with 95% confidence interval and categorical values
The comparison or control group may be allocated a placebo intervention, an alternative real intervention or no intervention at all.
1. RANDOMISED CONTROLLED TRIALS (Treatment studies) (Relevant JAMA User s Guides, Numbers IIA & B: references (3,4) Introduction: The most valid study design for assessing the effectiveness (both the benefits
GALA GENERAL ANAESTHESIA vs LOCAL ANAESTHESIA FOR CAROTID SURGERY HOSPITAL DISCHARGE OR 7 DAY POST-SURGERY FOLLOW-UP FORM
GALA GENERAL ANAESTHESIA vs LOCAL ANAESTHESIA FOR CAROTID SURGERY HOSPITAL DISCHARGE OR 7 DAY POST-SURGERY FOLLOW-UP FORM To the surgeon and anesthetist: Please complete questions 1-29 (pages 1, 2 & 3)
Management of haemorrhage in patients taking DOACs/ NOACs (direct/ novel oral anticoagulants) Guideline. Contents
Management of haemorrhage in patients taking DOACs/ NOACs (direct/ novel oral anticoagulants) Guideline Classification: Clinical Guideline Lead Author: Dr Rowena Thomas-Dewing, Consultant Haematologist
EAST MULTICENTER STUDY DATA DICTIONARY. Temporary Intravascular Shunt Study Data Dictionary
EAST MULTICENTER STUDY DATA DICTIONARY Temporary Intravascular Shunt Study Data Dictionary Data Entry Points and appropriate definitions / clarifications: Entry space Definition / Instructions 1. Specific
Efficient analysis of ordinal functional outcome scales
Efficient analysis of ordinal functional outcome scales Gordon D Murray University of Edinburgh Outline of presentation Functional outcome scales Ordinal analysis Case study: SCAST Results Points to consider
Statistics for Clinical Trials: Basics of Phase III Trial Design
Statistics for Clinical Trials: Basics of Phase III Trial Design Gary M. Clark, Ph.D. Vice President Biostatistics & Data Management Array BioPharma Inc. Boulder, Colorado USA NCIC Clinical Trials Group
Critical Review Form Therapy Objectives: Methods:
Critical Review Form Therapy Clinical Trial Comparing Primary Coronary Angioplasty with Tissue-Plasminogen Activator for Acute Myocardial Infarction (GUSTO-IIb), NEJM 1997; 336: 1621-1628 Objectives: To
Statistical Analysis Plan (SAP)
Statistical Analysis Plan (SAP) Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax in Ethiopia: a randomized controlled trial Contents
BLOOD PRESSURE-LOWERING TREATMENT
BLOOD PRESSURE-LOWERING TRIALS NUMBER OF PARTICIPANTS NUMBER OF PERCENTAGE OF MEAN AGE MEAN - (YEARS) TRIALS WITH ANALYSIS BY GENDER N, (%) 69,473 28,008 40.3% 70.2 3.2 3/5 (60%) APPENDIX 2 1 BLOOD PRESSURE-LOWERING
Clinical Study Synopsis
Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace
Meta Analysis. David R Urbach MD MSc Outcomes Research Course December 4, 2014
Meta Analysis David R Urbach MD MSc Outcomes Research Course December 4, 2014 Overview Definitions Identifying studies Appraising studies Quantitative synthesis Presentation of results Examining heterogeneity
The current place of tranexamic acid in the management of bleeding
Anaesthesia 2015, 70 (Suppl. 1), 50 53 Review Article doi:10.1111/anae.12910 The current place of tranexamic acid in the management of B. J. Hunt 1,2 1 Professor of Thrombosis & Haemostasis, Kings College
Anticoagulants and Head Injuries. Asaad Shujaa,MD,FRCPC,FAAEM Assistant Professor,weill Corneal Medicne Senior Consultant,HMC Qatar
Anticoagulants and Head Injuries Asaad Shujaa,MD,FRCPC,FAAEM Assistant Professor,weill Corneal Medicne Senior Consultant,HMC Qatar Common Anticoagulants and Indications Coumadin (warfarin) indicated for