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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02145182




Registration number
NCT02145182
Ethics application status
Date submitted
15/05/2014
Date registered
22/05/2014
Date last updated
17/12/2018

Titles & IDs
Public title
Prevention of Delayed Graft Function Using Eculizumab Therapy (PROTECT Study)
Scientific 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.
Secondary ID [1] 0 0
2013-004650-25
Secondary ID [2] 0 0
ECU-DGF-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Delayed Graft Function 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eculizumab
Treatment: Drugs - Placebo

Experimental: Active - 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 Comparator: Placebo - Placebo was administered by IV infusion over 25-45 min for 2 doses (on the day of transplant then 18-24 h later).


Treatment: Drugs: Eculizumab
Eculizumab is a complement component 5 inhibitor.

Treatment: Drugs: Placebo
0.9% sodium chloride

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
First 7 days post transplantation
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
First 7 days post transplantation
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
First 30 days post transplantation
Secondary outcome [3] 0 0
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).
Timepoint [3] 0 0
Day 28 post transplantation
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Week 26 and 52 post transplantation

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Westmead
Recruitment hospital [3] 0 0
- Adelaide
Recruitment hospital [4] 0 0
- Clayton
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Westmead
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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California
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Colorado
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Connecticut
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Georgia
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Illinois
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Kentucky
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Louisiana
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Missouri
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Washington
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São Paulo
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Nova Scotia
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Canada
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Quebec
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Czechia
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Prague
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Bordeaux
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Paris
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Suresnes
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Tours
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Germany
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Berlin
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Dresden
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Germany
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Erlangen
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Essen
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Hamburg
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Germany
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Hannoversch Münden
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Germany
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Hannover
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Germany
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Kiel
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Italy
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Bari
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Brescia
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Milano
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Torino
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Madrid
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Santander
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Sevilla
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Valencia
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Spain
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Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alexion Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
CTI Clinical Trial and Consulting Services
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02145182
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Contact person for public queries
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Summary results
Other publications