Prevention of Delayed Graft Function Using Eculizumab Therapy (PROTECT Study)
Primary Purpose
Delayed Graft Function
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Eculizumab
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Delayed Graft Function focused on measuring DGF, Dialysis, Kidney, Kidney Transplantation, eGFR, Complement, Eculizumab
Eligibility Criteria
Inclusion Criteria:
- Male or female, 18 years or older
- Has dialysis-dependent renal failure (initiated more than 2 months prior to transplant)
- Participant is to receive a first kidney transplant from a standard criteria donor or expanded criteria donor deceased donor with a DGF risk score using the Irish scale of ≥25% (to be determined prior to surgery and before randomization)
- Able to provide written informed consent
- Willing and able to comply with the requirements of the study protocol
- Female participants of child-bearing potential must have a negative serum pregnancy test (serum beta-human chorionic gonadotropin) and must be practicing an effective, reliable, and medically approved contraceptive regimen at the time of consent and for up to 5 months following discontinuation of treatment
Exclusion Criteria:
- Participant to receive a multi-organ transplant
- Participant to receive kidney(s) from donors <6 years of age
- Participant to receive a dual kidney transplant (from same donor, including en bloc)
- Participant to receive a living donor kidney
- Participant is highly sensitized (high risk to develop acute antibody-mediated rejection) to the donor (as determined by local center practice). Testing to determine high risk may include but is not limited to flow cytometric cross match, single antigen bead testing and/or complement dependent cytotoxicity
- Participant has received a previous transplant
- Participant is participating in another investigational study
- Participant has a body mass index >40 kilograms/square meter at screening
- Participant will be the recipient of an A, B, O Blood Glycoproteins (ABO) (blood type) incompatible kidney (A2 donors to B and O recipients will be allowed if the site has the ability to confirm A2 subtype)
- Participant will receive a kidney from a donation after cardiac death donor
- Participant has a predicted Irish model risk of DGF <25%
- Female participants who are pregnant or breast feeding
- Female participants of child bearing potential who are unable or unwilling to use a medically acceptable form of contraception
- Participants with a history of human immunodeficiency virus, or active hepatitis C virus or hepatitis B virus infection
- Participants with active bacterial or other infection which is clinically significant in the opinion of the Investigator
- Participants with a history of splenectomy
- Participants with unresolved meningococcal disease
- Participants with an unresolved systemic bacterial or fungal infection
- Participants with known or suspected hereditary complement deficiency (for example, but not limited to: atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria)
- Participant has a current malignancy or a history of any malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix that has been treated appropriately
- Participant has a history of or is believed by the Investigator to have used an illicit drug(s) and/or abused alcohol within 3 months prior to screening
- Participant has a psychiatric or physical illness that in the opinion of the Investigator would interfere with the ability of the participant to participate in the study
Sites / Locations
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Active
Placebo
Arm Description
Eculizumab was administered by intravenous (IV) infusion over 25-45 minutes (min) for 2 doses (on the day of transplant then 18-24 hours [h] later).
Placebo was administered by IV infusion over 25-45 min for 2 doses (on the day of transplant then 18-24 h later).
Outcomes
Primary Outcome Measures
Percentage Of Participants With Delayed Graft Function (DGF) In The First Seven Days Post-transplant
Results are reported for the DGF composite endpoint, defined as the occurrence of DGF (dialysis for any reason in the first 7 days post transplantation), graft loss, death, or loss to follow-up (including discontinuation) in the first 7 days post transplantation and for each item of the composite endpoint. Loss to follow-up included withdrawal due to any reason other than death. The sum of the counts in the events that make up the DGF composite may be greater than the composite count, because a participant who experienced multiple events was only counted once in the composite.
Secondary Outcome Measures
Percentage Of Participants With DGF, Functional DGF, And Immediate Graft Function
DGF was defined as a requirement for dialysis for any reason in the first 7 days post transplantation; functional DGF was defined as no need for dialysis during the first 7 days post transplantation and either (1) a <70% reduction in serum creatinine during the first 7 days post transplantation, or (2) failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days, both measured during the first 7 days post transplantation. Blood and urine samples were collected, but because the study failed to demonstrate a treatment effect and the program subsequently lost funding, the collected data from the samples could not be analyzed to generate summary level data. As such, the data set for this secondary outcome measure cannot be summarized.
Percentage Of Participants Who Required Dialysis Post Transplantation
The need for dialysis was assessed by evaluation of renal function; this included urine volume, blood urea nitrogen, serum creatinine, and, starting on Day 2, the creatinine reduction ratio. Blood and urine samples were collected, but because the study failed to demonstrate a treatment effect and the program subsequently lost funding, the collected data from the samples could not be analyzed to generate summary level data. As such, the data set for this secondary outcome measure cannot be summarized.
Estimated Glomerular Filtration Rate (eGFR)
The eGFR was calculated by using the Modification of Diet in Renal Disease 7 equation at Day 28 post transplantation. The equation requires serum creatinine, age, ethnicity, gender, blood urea nitrogen, and albumin. The eGFR was calculated retrospectively from participant demographics and laboratory chemistries and is reported in mL/min/square meter (m^2).
Percentage Of Participants With Rejection-free Graft Survival
Graft survival was defined as not having biopsy-proven acute rejection per Banff criteria, graft loss, or participant death. Participants who did not experience graft loss or death were censored at 365 days or the day they withdrew, whichever came first. There were no time-specific protocol mandated biopsies. Kidney biopsy would have been performed for cause at the discretion of the Investigator to assess poor graft function and would have been obtained prior to initiating treatment of suspected allograft rejection. Only summaries of Kaplan-Meier estimates of graft survival at Week 26 (Month 6) and Week 52 (Month 12) are reported.
Full Information
NCT ID
NCT02145182
First Posted
May 15, 2014
Last Updated
December 3, 2018
Sponsor
Alexion
Collaborators
CTI Clinical Trial and Consulting Services
1. Study Identification
Unique Protocol Identification Number
NCT02145182
Brief Title
Prevention of Delayed Graft Function Using Eculizumab Therapy (PROTECT Study)
Official Title
A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multi-center Study of Eculizumab for the Prevention of Delayed Graft Function After Kidney Transplantation in Adult Subjects at Increased Risk of Delayed Graft Function.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
August 21, 2014 (Actual)
Primary Completion Date
November 22, 2016 (Actual)
Study Completion Date
November 22, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
Collaborators
CTI Clinical Trial and Consulting Services
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study was to determine if eculizumab is safe and could be used to prevent delayed graft function (DGF) following kidney transplantation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Delayed Graft Function
Keywords
DGF, Dialysis, Kidney, Kidney Transplantation, eGFR, Complement, Eculizumab
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
288 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active
Arm Type
Experimental
Arm Description
Eculizumab was administered by intravenous (IV) infusion over 25-45 minutes (min) for 2 doses (on the day of transplant then 18-24 hours [h] later).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo was administered by IV infusion over 25-45 min for 2 doses (on the day of transplant then 18-24 h later).
Intervention Type
Drug
Intervention Name(s)
Eculizumab
Other Intervention Name(s)
Soliris
Intervention Description
Eculizumab is a complement component 5 inhibitor.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
0.9% sodium chloride
Primary Outcome Measure Information:
Title
Percentage Of Participants With Delayed Graft Function (DGF) In The First Seven Days Post-transplant
Description
Results are reported for the DGF composite endpoint, defined as the occurrence of DGF (dialysis for any reason in the first 7 days post transplantation), graft loss, death, or loss to follow-up (including discontinuation) in the first 7 days post transplantation and for each item of the composite endpoint. Loss to follow-up included withdrawal due to any reason other than death. The sum of the counts in the events that make up the DGF composite may be greater than the composite count, because a participant who experienced multiple events was only counted once in the composite.
Time Frame
First 7 days post transplantation
Secondary Outcome Measure Information:
Title
Percentage Of Participants With DGF, Functional DGF, And Immediate Graft Function
Description
DGF was defined as a requirement for dialysis for any reason in the first 7 days post transplantation; functional DGF was defined as no need for dialysis during the first 7 days post transplantation and either (1) a <70% reduction in serum creatinine during the first 7 days post transplantation, or (2) failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days, both measured during the first 7 days post transplantation. Blood and urine samples were collected, but because the study failed to demonstrate a treatment effect and the program subsequently lost funding, the collected data from the samples could not be analyzed to generate summary level data. As such, the data set for this secondary outcome measure cannot be summarized.
Time Frame
First 7 days post transplantation
Title
Percentage Of Participants Who Required Dialysis Post Transplantation
Description
The need for dialysis was assessed by evaluation of renal function; this included urine volume, blood urea nitrogen, serum creatinine, and, starting on Day 2, the creatinine reduction ratio. Blood and urine samples were collected, but because the study failed to demonstrate a treatment effect and the program subsequently lost funding, the collected data from the samples could not be analyzed to generate summary level data. As such, the data set for this secondary outcome measure cannot be summarized.
Time Frame
First 30 days post transplantation
Title
Estimated Glomerular Filtration Rate (eGFR)
Description
The eGFR was calculated by using the Modification of Diet in Renal Disease 7 equation at Day 28 post transplantation. The equation requires serum creatinine, age, ethnicity, gender, blood urea nitrogen, and albumin. The eGFR was calculated retrospectively from participant demographics and laboratory chemistries and is reported in mL/min/square meter (m^2).
Time Frame
Day 28 post transplantation
Title
Percentage Of Participants With Rejection-free Graft Survival
Description
Graft survival was defined as not having biopsy-proven acute rejection per Banff criteria, graft loss, or participant death. Participants who did not experience graft loss or death were censored at 365 days or the day they withdrew, whichever came first. There were no time-specific protocol mandated biopsies. Kidney biopsy would have been performed for cause at the discretion of the Investigator to assess poor graft function and would have been obtained prior to initiating treatment of suspected allograft rejection. Only summaries of Kaplan-Meier estimates of graft survival at Week 26 (Month 6) and Week 52 (Month 12) are reported.
Time Frame
Week 26 and 52 post transplantation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, 18 years or older
Has dialysis-dependent renal failure (initiated more than 2 months prior to transplant)
Participant is to receive a first kidney transplant from a standard criteria donor or expanded criteria donor deceased donor with a DGF risk score using the Irish scale of ≥25% (to be determined prior to surgery and before randomization)
Able to provide written informed consent
Willing and able to comply with the requirements of the study protocol
Female participants of child-bearing potential must have a negative serum pregnancy test (serum beta-human chorionic gonadotropin) and must be practicing an effective, reliable, and medically approved contraceptive regimen at the time of consent and for up to 5 months following discontinuation of treatment
Exclusion Criteria:
Participant to receive a multi-organ transplant
Participant to receive kidney(s) from donors <6 years of age
Participant to receive a dual kidney transplant (from same donor, including en bloc)
Participant to receive a living donor kidney
Participant is highly sensitized (high risk to develop acute antibody-mediated rejection) to the donor (as determined by local center practice). Testing to determine high risk may include but is not limited to flow cytometric cross match, single antigen bead testing and/or complement dependent cytotoxicity
Participant has received a previous transplant
Participant is participating in another investigational study
Participant has a body mass index >40 kilograms/square meter at screening
Participant will be the recipient of an A, B, O Blood Glycoproteins (ABO) (blood type) incompatible kidney (A2 donors to B and O recipients will be allowed if the site has the ability to confirm A2 subtype)
Participant will receive a kidney from a donation after cardiac death donor
Participant has a predicted Irish model risk of DGF <25%
Female participants who are pregnant or breast feeding
Female participants of child bearing potential who are unable or unwilling to use a medically acceptable form of contraception
Participants with a history of human immunodeficiency virus, or active hepatitis C virus or hepatitis B virus infection
Participants with active bacterial or other infection which is clinically significant in the opinion of the Investigator
Participants with a history of splenectomy
Participants with unresolved meningococcal disease
Participants with an unresolved systemic bacterial or fungal infection
Participants with known or suspected hereditary complement deficiency (for example, but not limited to: atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria)
Participant has a current malignancy or a history of any malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix that has been treated appropriately
Participant has a history of or is believed by the Investigator to have used an illicit drug(s) and/or abused alcohol within 3 months prior to screening
Participant has a psychiatric or physical illness that in the opinion of the Investigator would interfere with the ability of the participant to participate in the study
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
City
Livingston
State/Province
New Jersey
ZIP/Postal Code
07039
Country
United States
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
City
Camperdown
State/Province
New South Wales
Country
Australia
City
Westmead
State/Province
New South Wales
Country
Australia
City
Adelaide
State/Province
South Australia
Country
Australia
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
City
São Paulo
ZIP/Postal Code
05403-000
Country
Brazil
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Halifax
State/Province
Nova Scotia
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada
City
Prague
ZIP/Postal Code
14000
Country
Czechia
City
Bordeaux
ZIP/Postal Code
33076
Country
France
City
Créteil
ZIP/Postal Code
94010
Country
France
City
Le Kremlin-Bicêtre
ZIP/Postal Code
94270
Country
France
City
Lyon
ZIP/Postal Code
69003
Country
France
City
Nantes
ZIP/Postal Code
44093
Country
France
City
Paris
ZIP/Postal Code
75010
Country
France
City
Paris
ZIP/Postal Code
75743
Country
France
City
Strasbourg
ZIP/Postal Code
67091
Country
France
City
Suresnes
ZIP/Postal Code
92150
Country
France
City
Toulouse
ZIP/Postal Code
31059
Country
France
City
Tours
ZIP/Postal Code
37044
Country
France
City
Berlin
ZIP/Postal Code
13353
Country
Germany
City
Dresden
ZIP/Postal Code
01307
Country
Germany
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
City
Essen
ZIP/Postal Code
45147
Country
Germany
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
City
Hannoversch Münden
ZIP/Postal Code
34346
Country
Germany
City
Hannover
ZIP/Postal Code
30625
Country
Germany
City
Kiel
ZIP/Postal Code
24105
Country
Germany
City
Bari
ZIP/Postal Code
70124
Country
Italy
City
Brescia
ZIP/Postal Code
25123
Country
Italy
City
Milano
ZIP/Postal Code
20162
Country
Italy
City
Padova
ZIP/Postal Code
35128
Country
Italy
City
Torino
ZIP/Postal Code
10126
Country
Italy
City
Verona
ZIP/Postal Code
37126
Country
Italy
City
Badalona
ZIP/Postal Code
08916
Country
Spain
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
City
Madrid
ZIP/Postal Code
28041
Country
Spain
City
Santander
ZIP/Postal Code
39008
Country
Spain
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
City
Valencia
ZIP/Postal Code
46017
Country
Spain
City
Valencia
ZIP/Postal Code
46026
Country
Spain
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Prevention of Delayed Graft Function Using Eculizumab Therapy (PROTECT Study)
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