Implant or Graft; RejectionPhase 4NCT02152345
Belatacept Compared to Tacrolimus in Deceased Donor Renal Transplant Recipients
A Phase 4 study testing Belatacept, Tacrolimus and Mycophenolate in people with Implant or Graft; Rejection, run by Columbia University at 1 site in United States.
Trial summary
The main purpose of this study is to find out whether treatment to prevent kidney rejection with belatacept in presence of Thymoglobulin induction and withdrawal of steroids will result in less delayed graft function or "sleepy kidney" after transplant than that seen in patients who get tacrolimus as their main drug to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Implant or Graft; Rejection
- What is being tested?
- Belatacept, Tacrolimus and Mycophenolate
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to 31 Dec 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have known Epstein-Barr virus (EBV) serostatus, and that status must be positive
- Adult patients ≥18 years of age, receiving a deceased donor kidney transplant at Columbia University Medical Center (CUMC)
- Patients with a PRA ≤ of 50
- Primary or re-transplant candidates (no more than 5th renal transplant)
- Deceased donor renal transplant recipients
- Candidates eligible for rATG induction
- Patients fully consented prior to transplantation
- Women of reproductive age who are willing to delay pregnancy for the duration of the study and use appropriate recommended contraception
Who cannot join
- Seronegative or unknown EBV serologic status (due to the risk of post-transplant lymphoproliferative disorder, PTLD), predominantly involving the central nervous system.
- Patients with tuberculosis who have not been treated for latent infection.
- Scheduled to undergo multi-organ transplantation
- Recipients of previous non-renal organ transplant
- Patient receiving 5th renal transplant at the time of screening.
- Patients with a PRA > 50
Show all 15Show fewer
- Recipient is pre-emptive status.
- Recipient with positive flow crossmatch.
- History or known HIV
- Known hypersensitivity or contra-indications to Belatacept, Tacrolimus, Mycophenolate mofetil (cellcept), or mycophenolic acid
- Use of an investigational drug in the past 30 days before day of surgery
- Enrolled in a clinical trial other than the current
- Lactating or pregnant women
- Donor specific antibodies (DSA) identified at the time of transplantation
- ABO incompatible renal transplant
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: A Randomized Clinical Trial of Efficacy and Safety on the Use of Belatacept as Compared to Tacrolimus in the Setting of Rabbit Antithymocyte Globulin Induction and Rapid Steroid Discontinuation in Deceased Donor Renal Transplant Recipients With a Focus on Ameliorating Delayed Graft Function
The main purpose of this study is to find out whether treatment to prevent kidney rejection with belatacept in presence of Thymoglobulin induction and withdrawal of steroids will result in less delayed graft function or "sleepy kidney" after transplant than that seen in patients who get tacrolimus as their main drug to prevent rejection instead of belatacept. The investigators will also look at whether patients who get belatacept have the same, lesser or more problems that those who get tacrolimus.
Read the detailed description
New York Presbyterian Hospital-Columbia University Medical Center (NYPH-CUMC) performs nearly 250 renal transplants annually; of these approximately half are recipients of a variety of deceased donor kidneys, usually with cold ischemia time (CIT) >24 hours leading to an approximate incidence of delayed graft function (DGF) of 50%. The main focus of this study will be to determine whether initial immunosuppression with belatacept with Thymoglobulin induction will result in lower incidence and/or more rapid disappearance of DGF than that observed in patients who receive tacrolimus based immunosuppression. NGAL determinations will bne made in the first months after transplantation to correlate with clinical DGF.
- Conditions
- Implant or Graft; Rejection
- Being tested
- Belatacept, Tacrolimus, Mycophenolate, rATG, Methylprednisolone
- Keywords
- kidney, renal, transplant, belatacept, delayed graft function, thymoglobulin, tacrolimus, kidney function, immunosuppression, NGAL
- Medical subject headings
- Rejection, Psychology, Delayed Graft Function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelataceptDrug
Also called Nulojix
Belatacept 10 mg/kg will be administered in the operating room approximately 1 hour prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: Day 5, 14, 30, 56, and 84.
Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
TacrolimusDrug
Also called Prograf
Tacrolimus 0.05 mg/kg by mouth every 12 hours will be on Day 0 after transplantation. It will then be administered at 8-12 ng/mL on the following post-transplantation days: Day 3-90; at 8-10 ng/mL Day 91-180.
Tacrolimus 6 - 8 ng/mL will be administered daily thereafter until end of study.
(standard of care)
MycophenolateDrug
Also called Myfortic
An immunosuppressive agent used with other medicines to lower the body's natural immunity in patients who receive kidney transplants.
720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
(standard of care)
rATGDrug
Also called induction with rabbit anti-thymocyte globulin
1.5 mg/kg IV daily on Day 0-3.
(standard of care)
Also called Medrol
500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.
(standard of care)
Renal transplantProcedure or surgery
Also called Kidney transplant
Standard organ transplant of a kidney into a patient with end-stage renal disease.
| Study group | Role | What they receive |
|---|---|---|
| Belatacept Immunosuppression | Experimental | Renal transplant recipients will receive steroids (Methylprednisolone), rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation. Receives: Drug: Belatacept; Drug: Mycophenolate; Drug: rATG; Drug: Methylprednisolone; Procedure: Renal transplant |
| Standard Immunosuppression (Tacrolimus) | Active comparator | Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation. Receives: Drug: Tacrolimus; Drug: Mycophenolate; Drug: rATG; Drug: Methylprednisolone; Procedure: Renal transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Delayed Graft Function (DGF)
To assess whether treatment with Thymoglobulin induction and belatacept based maintenance immunosuppression would reduce delayed graft function (DGF) rates among recipients of deceased donor renal transplants as measured by clinical findings and NGAL marker, as specified below and defined by others. This will be compared to the incidence of DGF in patients treated with a Tacrolimus based regimen.
Patients who require hemodialysis in the first 7 days after transplantation and/or patients whose serum creatinine decreases <10% during 3 consecutive days after the transplant will be considered to have DGF in the absence of other confounding factors such as obstruction or infection. NGAL will be used as a verification marker of DGF.
Measured: Up to 3 months post-transplantation
Secondary outcomes (3)
Percentage of Participants With Allograft Survival
Allograft survival is defined as functioning renal transplant.
Measured: Up to 1 year post-transplantation
Number of Participants With an Allograft Rejection Episode
All rejection episodes will be confirmed by renal transplant biopsy provoked by change in renal function not explained by other clinical causes.
Measured: Up to 1 year post-transplantation
Estimated Glomerular Filtration Rate (eGFR)
Estimated glomerular filtration rate (eGFR) is based on a blood sample (serum creatinine value), age, race, and gender. eGFR estimates best the function of the kidney at any one time.
Measured: Up to 1 year post-transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2014 (estimated)
- Study startJun 2014
- Primary completion31 Dec 2016
- Study completion31 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Implant or Graft; RejectionStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mark A Hardy, Columbia University
- Investigators
- Mark A. Hardy, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02152345
- Sponsor's protocol ID
- AAAL7011
- Status last verified
- Jan 2021
- First submitted
- 29 May 2014
- Last updated
- 10 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Clinical Trial of Efficacy and Safety on the Use of Belatacept as Compared to Tacrolimus in the Setting of Rabbit Antithymocyte Globulin Induction and Rapid Steroid Discontinuation in Deceased Donor Renal Transplant Recipients With a Focus on Ameliorating Delayed Graft Function
- ClinicalTrials.gov ID
- NCT02152345
- Acronym / sponsor ID
- AAAL7011
- Conditions
- Implant or Graft; Rejection
- Keywords
- kidney, renal, transplant, belatacept, delayed graft function, thymoglobulin, tacrolimus, kidney function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 31 Dec 2016 (actual)
- First posted
- 2 Jun 2014 (estimated)
- Results
- Posted 10 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to find out whether treatment to prevent kidney rejection with belatacept in presence of Thymoglobulin induction and withdrawal of steroids will result in less delayed graft function or "sleepy kidney" after transplant than that seen in patients who get tacrolimus as their main drug to prevent rejection instead of belatacept. The investigators will also look at whether patients who get belatacept have the same, lesser or more problems that those who get tacrolimus.
Detailed description
New York Presbyterian Hospital-Columbia University Medical Center (NYPH-CUMC) performs nearly 250 renal transplants annually; of these approximately half are recipients of a variety of deceased donor kidneys, usually with cold ischemia time (CIT) >24 hours leading to an approximate incidence of delayed graft function (DGF) of 50%. The main focus of this study will be to determine whether initial immunosuppression with belatacept with Thymoglobulin induction will result in lower incidence and/or more rapid disappearance of DGF than that observed in patients who receive tacrolimus based immunosuppression. NGAL determinations will bne made in the first months after transplantation to correlate with clinical DGF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Belatacept Immunosuppression | Experimental | Drug: Belatacept, Drug: Mycophenolate, Drug: rATG, Drug: Methylprednisolone, Procedure: Renal transplantRenal transplant recipients will receive steroids (Methylprednisolone), rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation. |
| Standard Immunosuppression (Tacrolimus) | Active comparator | Drug: Tacrolimus, Drug: Mycophenolate, Drug: rATG, Drug: Methylprednisolone, Procedure: Renal transplantRenal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must have known Epstein-Barr virus (EBV) serostatus, and that status must be positive
- Adult patients ≥18 years of age, receiving a deceased donor kidney transplant at Columbia University Medical Center (CUMC)
- Patients with a PRA ≤ of 50
- Primary or re-transplant candidates (no more than 5th renal transplant)
- Deceased donor renal transplant recipients
Key exclusion criteria (15 listed)
- Seronegative or unknown EBV serologic status (due to the risk of post-transplant lymphoproliferative disorder, PTLD), predominantly involving the central nervous system.
- Patients with tuberculosis who have not been treated for latent infection.
- Scheduled to undergo multi-organ transplantation
- Recipients of previous non-renal organ transplant
- Patient receiving 5th renal transplant at the time of screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelataceptAlso: NulojixBelatacept 10 mg/kg will be administered in the operating room approximately 1 hour prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: Day 5, 14, 30, 56, and 84. Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study. | Drug | Belatacept Immunosuppression |
| TacrolimusAlso: PrografTacrolimus 0.05 mg/kg by mouth every 12 hours will be on Day 0 after transplantation. It will then be administered at 8-12 ng/mL on the following post-transplantation days: Day 3-90; at 8-10 ng/mL Day 91-180. Tacrolimus 6 - 8 ng/mL will be administered daily thereafter until end of study. (standard of care) | Drug | Standard Immunosuppression (Tacrolimus) |
| MycophenolateAlso: MyforticAn immunosuppressive agent used with other medicines to lower the body's natural immunity in patients who receive kidney transplants. 720 mg by mouth every 12 hours (Day 0)(1080 mg AA). (standard of care) | Drug | Belatacept Immunosuppression, Standard Immunosuppression (Tacrolimus) |
| rATGAlso: induction with rabbit anti-thymocyte globulin1.5 mg/kg IV daily on Day 0-3. (standard of care) | Drug | Belatacept Immunosuppression, Standard Immunosuppression (Tacrolimus) |
| MethylprednisoloneAlso: Medrol500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3. (standard of care) | Drug | Belatacept Immunosuppression, Standard Immunosuppression (Tacrolimus) |
| Renal transplantAlso: Kidney transplantStandard organ transplant of a kidney into a patient with end-stage renal disease. | Procedure or surgery | Belatacept Immunosuppression, Standard Immunosuppression (Tacrolimus) |
Primary outcome
Number of Participants With Delayed Graft Function (DGF)
Time frame: Up to 3 months post-transplantation
To assess whether treatment with Thymoglobulin induction and belatacept based maintenance immunosuppression would reduce delayed graft function (DGF) rates among recipients of deceased donor renal transplants as measured by clinical findings and NGAL marker, as specified below and defined by others. This will be compared to the incidence of DGF in patients treated with a Tacrolimus based regimen. Patients who require hemodialysis in the first 7 days after transplantation and/or patients whose serum creatinine decreases <10% during 3 consecutive days after the transplant will be considered to have DGF in the absence of other confounding factors such as obstruction or infection. NGAL will be used as a verification marker of DGF.
3 secondary outcomes
Percentage of Participants With Allograft Survival
Time frame: Up to 1 year post-transplantation
Number of Participants With an Allograft Rejection Episode
Time frame: Up to 1 year post-transplantation
Estimated Glomerular Filtration Rate (eGFR)
Time frame: Up to 1 year post-transplantation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark A. Hardy, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Belatacept, Tacrolimus and Mycophenolate in people with Implant or Graft; Rejection, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Delayed Graft Function (DGF) (time frame: Up to 3 months post-transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2021.