Supplementary Appendix

Transcription

1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Niemann CU, Feiner J, Swain S, et al. Therapeutic hypothermia in deceased organ donors and kidney-graft function. N Engl J Med 2015;373: DOI: /NEJMoa

2 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Claus U. Niemann 1,2, MD, John Feiner 1, MD, Sharon Swain 3, MSN, RN, Scott Bunting 4,RRT, Melissa Friedman 4, MSN, RN, Megan Crutchfield 5, MPH, Kristine Broglio MS, 6 Ryutaro Hirose 2, MD, John P. Roberts 2, MD, and Darren Malinoski 5,7, MD 1 Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, 2 Department of Surgery, Division of Transplantation, University of California San Francisco, California, United States, 3 California Transplant Donor Network, Oakland, California, 4 OneLegacy, Los Angeles, California, 5 Section of Surgical Critical Care, VA Portland Health Care System (VAPORHCS), Portland, Oregon 6 Berry Consultants, LLC Austin, Texas, 7 Division of Trauma, Critical Care, and Acute Care Surgery, Oregon Health & Science University, Portland, Oregon 1

3 Table of Contents Personnel and Funding 4 Principal Investigator (s): 4 Statistician 4 Independent Data Safety and Monitoring Board 4 Trial Coordinators 4 Sites, principal investigators and investigators 4 Funding 4 Acknowledgement 4 Methods Supplement 6 Study design: 6 Data gathering: 6 Data analysis 6 Data and analysis integrity 6 Manuscript: 6 Decision to publish: 6 Authorization Process for Donation and Research 6 Communication with Transplant Centers 7 Table S1. United Network for Organ Sharing Region 5 donor management goals. 9 Inclusion and Exclusion Criteria 9 Inclusion Criteria 9 Exclusion Criteria 9 Temperature Management and Intervention 11 Data Collection and Verification 11 Data Entry 11 Donor-specific Data 12 Recipient-specific Data 12 Security and Privacy 13 Administration 13 Reporting 13 Results Supplement 14 Interim Analysis 14 Temperature Profiles in Study Groups 14 Table S2. Temperature and cooling data for donors who donated at least one kidney. 15 Table S3. Characteristics of All Enrolled Organ Donors. 16 Adverse events Err or! Bookmark not defined. Table S4. Additional Organ Recipient Characteristics. 16 Subgroup Analyses 18 2

4 Kidney-Pancreas Transplants 18 Liver-Kidney Recipients 18 Table S5. Subgroup Analyses 18 Secondary Outcomes 19 Table S6. Organs Transplanted by Treatment Group 19 Selective active Trials investigating Interventions on Delayed Graft Function 20 3

5 Supplementary Appendix Personnel and Funding Principal Investigator (s): PI: Claus Niemann, University of California San Francisco, USA, Co-PI Darren Malinoski, Portland VA Medical Center & Oregon Health & Science University, Statistician Berry Consultants, 4301 Westbank Dr #140B, Austin,TX Independent Data Safety and Monitoring Board Roger J. Lewis, MD, PhD, Department of Emergency Medicine Harbor-UCLA Medical Center, Bldg D9, 1000 W Carson St, Torrance, CA Torrance, CA, USA Trial Coordinators Sharon Swain, Scott Bunting, Megan Crutchfield, Darren Malinoski and Claus Niemann Sites, principal investigators and investigators California Transplant Donor Network: Claus Niemann (PI), Sharon Swain, John P. Roberts, Ryutaro Hirose, John Feiner OneLegacy: Darren Malinoski (Co-PI), Scott Bunting, Megan Crutchfield Funding This publication was supported by Grant No. R380T22183 (to Claus U. Niemann, MD) from the Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services. Acknowledgement The data reported here have been supplied by the Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The 4

6 interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government. We also would like to thank Nathan Tomlanovich for his help with data management. In addition we would like to thank James Bowman, MD and Bernard F. Kozlovsky, MD from the Health Resources and Services Administration for his continuous encouragement. In addition, we would like to thank Tom Mone (OneLegacy) and Crystal Oley-Graybill (UNOS) for their support. 5

7 Methods Supplement Study design Claus U. Niemann, MD, Darren Malinoski, MD Data gathering John Feiner, MD, Sharon Swain, MSN, RN, Scott Bunting, RRT, Melissa Friedman, MSN, RN, Megan Crutchfield, MPH Data analysis Claus U. Niemann, MD, Darren Malinoski, MD, John Feiner, MD, Kristine Broglio MS, Ryutaro Hirose, MD, John P. Roberts, MD Data and analysis integrity Claus U. Niemann, MD, Darren Malinoski,MD, John Feiner, MD, Megan Crutchfield, MPH, Kristine Broglio MS, Ryutaro Hirose, MD, John P. Roberts, MD Manuscript Claus U. Niemann, MD, Darren Malinoski, MD, John Feiner, MD, Kristine Broglio MS, Ryutaro Hirose, MD, John P. Roberts, MD Decision to publish Claus U. Niemann, MD, Darren Malinoski, MD Authorization Process for Donation and Research Upon declaration of neurologic death, patients families or legal surrogates either received disclosure of a patient s prior document of gift for organ and tissue donation on the California 6

8 State Donor Registry or were approached for authorization for donation. Unless otherwise specified, a patient s document of gift included authorization for research. Research authorization to enroll DNDDs in management studies or utilize their organs and/or tissue could either be documented by the donor on a state registry prior to their death or, in the absence of this, obtained from their legal next of kin after the decision to donate organs had been made. At the time that families or legal surrogates were approached for authorization for organ and tissue donation, a request for authorization for research was also made. The family or surrogate could authorize or decline research participation independent of organ and tissue donation for transplantation. If authorization for research was granted a research brochure was provided explaining the current research the OPO was engaged in. If a family or surrogate declined research due to objections over solid organs being utilized solely for research an additional request was made to determine if enrollment in this trial was feasible as the trial did not involve procurement of organs solely for research purposes. If authorization was granted, an addendum was made to the authorization form specifically stating authorization for enrollment in this donor management trial. Legal statutes do not require informed consent from next of kin, due to the fact that no harm can come to a deceased subject. However, the Uniformed Anatomical Gift Act does require authorization for both what is being donated as well as the purpose for which the gift is being donated, organ transplantation and research being two such examples. Communication with Transplant Centers Prior to implementation of the study, contact was initiated with all of the high volume donor hospitals and local transplant centers in the two donation service areas covered by OneLegacy and California Transplant Donor Network to inform them of this research effort. The research oversight body of each OPO approved the study protocol after each of their organ-specific 7

9 committees provided input. Two exclusion criteria were suggested and adopted: DNDDs with (1) hemodynamic instability, defined as not meeting the UNOS Region 5 Donor Management Goal for low-dose vasopressor usage or (2) a coagulopathy, defined as an INR > 2.5, PTT > 3x normal, and/or a Platelet count < 50,000/mcl. Table S1 contains the current UNOS DMGs, which include the criteria for hemodynamic instability and guide the bedside management of every DNDD throughout the Region. After receiving local approval, the study protocol was presented to the UNOS Region 5 Research Committee, which recommended approval to the general audience at the Regional Business Meeting. Approval was given with the following stipulations: 1. Split liver donors should not be included due to the concern for a mild coagulopathy during the dissection of donors in the hypothermia arm and 2. Donors of thoracic organs should be excluded until the cardiovascular and pulmonary safety profile of mild hypothermia could be established and presented at the next meeting of the Research Committee. In addition, notification was sent via the United Network for Organ Sharing (UNOS) enewsletter to inform the transplant community at large about the upcoming study and to allow for a two-week public comment period, during which time no further requests were made. Study protocols were made available on and shared as requested. With each subject enrollment, information about organs offered for transplantation from enrolled DNDDs was posted on DonorNet SM, (Richmond, Virginia, USA). In addition to standard data, it contained information about the study protocol and treatment group assignment. This allowed any transplant center and surgeon to contact the PI or Co-PI at any time if there were questions concerning donor enrollment and the implications for organs offered for transplantation. The allocation of organs to specific recipients occurred based on standard OPTN guidelines and local transplant center acceptance criteria. 8

10 Table S1. United Network for Organ Sharing Region 5 donor management goals. Donor Management Goals Mean arterial pressure Central venous pressure Ejection fraction Vasopressors* Arterial blood gas ph PaO 2 /FIO 2 Serum Sodium Urine output Parameters mm Hg 4 12 mm Hg 50% 1 and low dose mmol/l > 0.5 ml/kg/hr over 4 hrs Glucose 180 mg/dl *Low dose of vasopressors was defined as: Dopamine 10 mcg/kg/min, Phenylephrine 60 mcg/min, and Norepinephrine 10 mcg/min Inclusion and Exclusion Criteria Inclusion Criteria Legal determination of death by neurologic criteria Any gender or ethnicity Age 18 years or greater at the time of death Authorization for research from the authorizing surrogate or by First Person Authorization via either a state donor registry or advanced directive Mean arterial blood pressure > 60 mmhg for more than one hour without an increase in vasopressors (see exclusion criteria for upper limits of vasopressor use) Exclusion Criteria Donors after determination of circulatory death (DCD) Age under 18 years 9

11 No research authorization End stage renal disease and/or dialysis at the time of current hospitalization Coagulopathy (INR greater than 2.5, PTT greater than 3 time normal, and/or platelet count less than 50,000/mcl), Hemodynamic instability (more than one vasopressor or one agent at a high dose: dopamine greater than 10 mcg/kg/min, norepinephrine greater than 10 mcg/min, and/or phenylephrine greater than 60 mcg/min) Donor considered a candidate for in-situ split liver Chronic medical condition precluding general acceptance for transplantation (i.e. Hepatitis B or C, diabetic or hypertensive nephropathy with unacceptable kidney biopsy findings) Additional outlying factors for exclusion were determined on a case-by-case basis with the PI and the study coordinator (i.e. severe electrolyte disturbance, rhabdomyolysis, etc.) Of note, donors whose coagulopathy, hemodynamic instability, or electrolyte deficiency were corrected, were considered for enrollment at that time. DNDDs were disenrolled if any of these exclusion criteria developed after randomization, but before initiation of targeted temperature management, or a donor family rescinded authorization for either donation or research. In addition, based on the initial approval that was received by each OPO s research oversight body as well as the UNOS Region 5 Research Committee, DNDDs who were anticipated to be thoracic organ donors (heart/lung) were excluded during the first 6 months of the study so that the safety profile of mild hypothermia on hemodynamic and respiratory function could be established; being that deep hypothermia has been associated with a decrease in cardiac output and no amount of hypothermia has previously been studied in DNDDs, thoracic transplant programs wanted to examine these effects prior to accepting organs 10

12 from study donors. After a detailed safety analysis was shared with regional thoracic transplant programs (see below), enrollment was then expanded to include all DNDDs with research authorization: Enrollment began on March 15, 2012 and, as of December 6th, there have been 123 donors randomized. Initially, only abdominal donors were included so that the cardiovascular and respiratory effects of mild hypothermia could be assessed and a safety analysis performed. The analysis has revealed that no donors have required an increase in vasopressor dosages after enrollment and there were no significant changes in PaO 2 :FIO 2 ratios over time in either group. Temperature Management and Intervention The intervention was initiated after research authorization was obtained and randomization had occurred. Randomized DNDDs were either warmed to or cooled to C based on the study group assignment. The goal was to reach the target temperature within four hours of enrollment. Once this target was reached, temperature was maintained within the goal range until the DNDD was transported to the operating room for organ recovery. Management in the operating room was not part of the donor intervention and followed standard protocols. Data Collection and Verification Data Entry OPO procurement coordinators prospectively entered the data contained within the DMG data template at the bedside of each donor during donor management. This data template has been in place since 2008 and has been extensively used for quality assurance. Its overall format and functionality are familiar to all of the OPOs in Region 5. Study protocol-specific data were prospectively recorded on an electronic data collection sheet, reviewed during weekly conference calls by the steering committee, and imported into a relational database (Filemaker 11

13 Pro, Santa Clara, CA, USA). The relational database allowed for matching of all donor-specific data to the appropriate recipient demographic and outcome data that was provided by the Scientific Registry of Transplant Recipients (SRTR). Donor-specific Data Donor demographics, medical history and baseline clinical data were collected along with laboratory values obtained at the time of enrollment from the OPO. Time intervals between ICU admission, study enrollment, and organ recovery were recorded. Creatinine levels were used for calculation of GFR (Modification of Diet in Renal Disease Study, Creatinine and GFR were measured at study enrollment and just prior to organ recovery (terminal creatinine). The Kidney Donor Profile Index (KDPI) is cumulative percentage scale that represents an overall estimate of the risk of graft failure for an individual donor. The KDPI includes weight, height, ethnicity/race, history of hypertension or diabetes, cause of death, serum creatinine, anti-hcv. Recipient-specific Data The study obtained data from the Scientific Registry of Transplant Recipients (SRTR). The SRTR data system includes data on all donors, wait-listed candidates, and transplant recipients in the US, submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors. Recipient variables known to impact graft function and that are included in established riskadjusted models were obtained from the SRTR standard analysis file ( and linked to each study donor by their unique UNOS identification number. These included recipient age, sex, ethnicity, cold ischemia time, 12

14 and warm ischemia time, among others. The full model is available at: Security and Privacy The Region funded the creation of a web portal (software as a service, SAAS) for more efficient and accurate data entry. The web based data entry system employs a rights management system through which system administrators can control and maintain user responsibilities and privileges. The system provides a login page requesting a unique user name and password for the purpose of authenticating the appropriate user access levels and privileges. System access beyond this point is restricted to only allow authorized users of the system. Once a user login is processed and authenticated, the system creates a security session. Session data tracks the user and the system checks the security session each time the user accesses a page. Administration One person at each OPO was given administrative rights to manage the application in terms of security authorizations and registering and un-registering each OPO s users. Reporting Data gathered were consolidated into report formats and exportable for analysis purposes. Reports were generated for each OPO as well as OPO-blinded aggregate reports. 13

15 Results Supplement Interim Analysis Sample size estimation was based on the primary outcome, DGF. We considered a 30% relative change in the DGF rate to be considered clinically significant. In order to have 90% power to detect this change with an overall two-sided Type I error rate of 5%, this trial required a total of 820 kidneys transplanted, 410 in each group. With an estimated attrition rate of 20%, our original enrollment target was 500 donors or 1000 potentially transplantable kidneys. At the time of the interim analysis, 293 DNDDS were enrolled and 247 had at least one kidney transplanted. The primary endpoint was known on at least one kidney from 244 donors. Based on the Lan-DeMets approximation of the O Brien-Fleming group sequential boundary and an information time of 244/500 (48.8% information), the two-sided nominal p-value for treatment required to stop early for success was and the p-value required for success at the completion of the trial would be At the interim analysis, based on the primary efficacy analysis, hypothermia reduced the odds of DGF by approximately half (OR = 0.49, 95% confidence interval [CI] 0.32 to 0.75) as compared to normothermia. The two-sided p-value for treatment group was 0.001, which was less than the two-sided p-value required for early success stopping (0.0026). Accrual to the trial was not paused for the interim analyses Temperature Profiles in Study Groups Temperature did not differ initially between donors in the hypothermia and normothermia group (Table S2). Upon leaving for the operating room for organ donation, donors in the hypothermia group were over 2ºC colder than those in the normothermia group (P<0.001). 14

16 Table S2. Temperature and cooling data for donors who donated at least one kidney. Hypothermia Normothermia P Value (N = 150) (N = 152) Temperature (ºC) Enrollment 36.5 ± ± Prior to organ recovery 34.6 ± ± 0.4 < Method of Temperature Control < Arctic Sun 5 (3.3) 0 (0.0) Bair Hugger 0 (0.0) 9 (5.9) Blanket 112 (74.7) 81 (53.3) Fan 4 (2.7) 4 (2.6) Ice Packs 7 (4.7) 2 (1.3) None 13 (8.7) 51 (33.6) Other 7 (4.7) 3 (2.0) Unknown 2 (1.3) 2 (1.3) Core Temperature Measurement 0.43 Bladder 57 (38.3) 72 (47.4) Esophageal 1 (0.7) 1 (0.7) Rectal 85 (57.0) 75 (49.3) Other 6 (4.0) 4 (2.6) Target Temperature Reached in 4 hours 122 (81.3%) 149 (98.0%) < Time at Target Temperature (hours) 16.9 ( ) n/a* Data are mean ± SD or No. (%), or median (interquartile range). Data missing for 1 donor in hypothermia group; * all donors were in the normothermic range at enrollment Characteristics of All Enrolled Kidney Donors The characteristics of all enrolled donors were balanced between the treatment groups, including the three stratification criteria and the KDPI (Table S3). A single donor had both kidneys pumped. 15

17 Table S3. Characteristics of All Enrolled Organ Donors. Hypothermia Group Normothermia Group (N = 180) (N = 190) P Value OPO n. (%) 0.83 A 77 (42.8) 84 (44.2%) B 103 (57.2) 106 (55.8) Age yr 46 ± ± Sex n. (%) 0.39 Female 69 (38.3) 64 (33.7) Male 111 (61.7) 126 (66.3) Height m 1.70 ± ± Weight kg 83.7 ± ± Body Mass Index kg/m ± ± ECD at enrollment n. (%) 60 (33.3) 64 (33.7) 1.0 KDPI* % 55 ± ± Prior Hypothermia n. (%) 20 (11.1) 21 (11.1) 1.0 Enrollment Creatinine mg/dl 1.2 ± ± Terminal Creatinine mg/dl 1.1 ± ± Enrollment GFR ml/min/1.73m ± ± Terminal GFR ml/min/1.73m ± ± Plus-minus values are means±sd OPO, organ procurement organization; ECD, expanded criteria donor; KDPI, Kidney Donor Profile Index; GFR, glomerular filtration rate; Terminal creatinine, last creatinine recorded in the ICU *Data missing for 11 donors in the hypothermia group and 8 donors in the normothermia group Additional Recipient organ recipient characteristics are shown in Table S4 Table S4. Additional Organ Recipient Characteristics. Hypothermia Group Normothermia Group (N = 285) (N = 287) P Value Height m 0.61 N

18 mean ± SD 167 ± ± 15 Weight kg 0.55 N mean ± SD 76.0 ± ± 20.5 Donor/Recipient Weight Ratio 0.94 N mean ± SD 1.20 ± ± 0.71 HCV 0.31 N no. (%) 10 (4.3) 15 (6.5) HLA Mismatches 0.92 N mean ± SD 4 ± 2 4 ± 2 Peak PRA 0.91 N mean ± SD 20 ± ± 31 Placed Outside Original DSA N no. (%) 35 (14.9) 50 (21.0) Time on RRT days 0.48 N mean ± SD 2,061 ± 1,375 2,030 ± 1,523 RRT 30 days 210 (95.0) 210 (95.5) 1.0 Prior Renal Transplant N no. (%) 26 (11.1) 26 (10.9) 1.0 Plus-minus values are means±sd; N, count of available data HCV, hepatitis C virus; HLA, human leukocyte antigen; PRA, plasma reactive antibody; RRT, renal replacement therapy; DSA, donor service area 17

19 Subgroup Analyses Within each subgroup, DGF between treatment groups was compared with a logistic regression model fitted according to the GEE and including only a term for randomized treatment group. Kidney-Pancreas Transplants Combined kidney-pancreas transplants included 16 (5.6%) kidneys from the hypothermia group of donors and 10 (3.5%) from donors in the normothermia group. No ECD donors were used for combined kidney-pancreas transplant and no DGF occurred in either treatment group (Table S5). Liver-Kidney Recipients Simultaneous kidney and liver grafts, included 12 (4.2%) kidneys from the hypothermia group and 13 (4.5%) from the normothermia group. Only 5 of these 25 donors were ECD. The proportion of DNDDs who donated kidney and liver grafts to the same recipient was not significantly different between the two treatment groups (P=1.0). DGF in kidneys from the two treatment groups did not differ within this subgroup, P= (Table S5). Table S5. Subgroup Analyses Hypothermia Group Normothermia Group (N = 280*) (N = 286*) Odds Ratio (95% CI) P Value Liver-kidney No. (%) 12 (4.3) 13 (4.5) DGF 9 (75.0) 6 (46.2) 3.5 (0.64 to 19.2) 0.15 Kidney-pancreas No. (%) 16 (5.7) 10 (3.5) DGF 0 (0) 0 (0) 1.0 Data are No. (%), or odds ratio (95% confidence interval) DGF, delayed graft function; ECD, expanded criteria donor; SCD, standard criteria donor *Only recipients with complete DGF and cold ischemic time data were included 18

20 Secondary Outcomes In both treatment groups the median number of organs transplanted from each donor was 3 (interquartile range, 2-4, P=0.987, Table S6) and individual organ transplantation rates were similar between groups. Table S6. Organs Transplanted by Treatment Group Hypothermia Group Normothermia Group (N = 180) (N = 190) P Value Number of Organs Transplanted Total Mean ± SD 3.2 ± ± Median (interquartile range) 3.0 ( ) 3.0 ( ) 0.87 Kidneys 0.70 Both 140 (77.8) 141 (74.2) One 10 (5.6) 11 (5.8) None 30 (16.7) 38 (20.0) Number of Kidneys Transplanted Total Mean ± SD 1.6 ± ± Median (interquartile range) 2.0 ( ) 2.0 ( ) 0.41 Heart Transplanted 46 (25.6) 49 (25.8) 1.0 Liver Transplanted 129 (71.7) 135 (71.1) 0.91 Lungs Transplanted 0.79 Both 40 (22.2) 44 (23.2) One 3 (1.7) 5 (2.6) None 137 (76.1) 141 (74.2) Pancreas or Islets Transplanted 19 (10.6) 15 (7.9) 0.47 Data are mean ± SD, median (interquartile range), No., or No. (%) 19

21 Selective registered trials (ClinicalTrials.gov) with delayed graft function as an endpoint. Accessed: April 27, 2015 Identifier: NCT Belatacept for Renal Transplant Recipients With Delayed Graft Function This study is currently recruiting participants. Verified May 2014 by Ohio State University Sponsor: Von Visger, Jon, MD Collaborator: Bristol-Myers Squibb Information provided by (Responsible Party): Von Visger, Jon, MD, The Ohio State University First received: April 21, 2014 Last updated: May 7, 2014 Last verified: May 2014 ClinicalTrials.gov Identifier: NCT Eculizumab for Prevention of Delayed Graft Function (DGF) in Kidney Transplantation This study is currently recruiting participants. Verified March 2015 by Heeger, Peter, M.D. 20

22 Sponsor: Heeger, Peter, M.D. Collaborators: Alexion Pharmaceuticals Mount Sinai School of Medicine Information provided by (Responsible Party): Heeger, Peter, M.D. First received: August 7, 2013 Last updated: March 17, 2015 Last verified: March 2015 ClinicalTrials.gov Identifier: NCT A Trial for the Prevention of DGF After Kidney Transplantation This study is currently recruiting participants. Verified April 2015 by Alexion Pharmaceuticals Sponsor: Alexion Pharmaceuticals Collaborator: CTI Clinical Trial and Consulting Services Information provided by (Responsible Party): Alexion Pharmaceuticals First received: May 15, 2014 Last updated: April 13, 2015 Last verified: April

23 ClinicalTrials.gov Identifier: NCT Study on Delayed Graft Function Using Paired Kidneys This study is currently recruiting participants. Verified January 2015 by Angion Biomedica Corp Sponsor: Angion Biomedica Corp Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Information provided by (Responsible Party): Angion Biomedica Corp ClinicalTrials.gov Identifier: NCT First received: March 21, 2012 Last updated: January 13, 2015 Last verified: January 2015 ClinicalTrials.gov Identifier: NCT Placebo-Controlled Study to Evaluate the Safety and Efficacy of OPN-305 in Preventing Delayed Renal Graft Function This study is currently recruiting participants. Verified March 2015 by Opsona Therapeutics Ltd. 22

24 Sponsor: Opsona Therapeutics Ltd. Information provided by (Responsible Party): Opsona Therapeutics Ltd. First received: February 13, 2013 Last updated: March 17, 2015 Last verified: March 2015 ClinicalTrials.gov Identifier: NCT C1INH Inhibitor Preoperative and Post Kidney Transplant to Prevent DGF & IRI (C1INHDGF) This study is currently recruiting participants. Verified September 2014 by Cedars-Sinai Medical Center Sponsor: Cedars-Sinai Medical Center Information provided by (Responsible Party): Stanley Jordan, MD, Cedars-Sinai Medical Center First received: February 19, 2014 Last updated: September 26, 2014 Last verified: September 2014 Please visit for completed trials and additional information. 23