Belatacept in obese kidney transplant recipients

Lead Investigator: Nicholas Lange, Columbia University
Title of Proposal Research: Belatacept in obese kidney transplant recipients
Vivli Data Request: 6860
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Belatacept is a safe and effective option for immunosuppression in kidney transplant recipients. Belatacept is dosed based on patients’ actual body weight at the time of transplantation. To date, there has not been a rigorous evaluation on the impact of obesity among kidney transplant recipients receiving belatacept-based immunosuppression. The objective of this study is to evaluate outcomes after transplantation among obese versus non-obese kidney transplant recipients being treated with belatacept.

Statistical Analysis Plan:

All BENEFIT and BENEFIT-EXT participants will be included in this analysis. Participants will be stratified by BMI category as defined above (normal weight, overweight, obese, morbidly obese). Descriptive statistics will be used to compare baseline characteristics between these groups, as well as between participants who received cyclosporine versus belatacept within each BMI category.

Unadjusted and adjusted logistic regression will be used to compare the odds of biopsy-proven acute rejection among participants who received belatacept versus cyclosporine in each BMI category (e.g. morbidly obese participants receiving belatacept vs. morbidly obese participants receiving cyclosporine).

Unadjusted and adjusted time-to-event analysis will be used to compare the hazard of biopsy-proven acute rejection by BMI category within the belatacept group and within the cyclosporine group.

Time-to-event analysis will also be used to compare death-censored allograft survival and patient survival.
Based on the primary endpoint of patient and graft survival, we estimate that a sample size of 852 is needed for a power of 80% to detect a difference of 6% between groups, with an alpha of 5%. This will be easily achieved by combining the BENEFIT and BENEFIT-EXT cohorts (total sample size > 1200).

Data will be secured using a password-protected endpoint device and will only be accessible by the investigators (Drs. Demetra Tsapepas, Sumit Mohan, Syed Ali Husain, Jessica Hedvat and Nicholas Lange).

Potential identifiers would include date of birth and date of transplant. No other PHI identifiers would be required to complete the analyses. A master list of these identifiers matching subject # to identifiers will be maintained in a locked drawer. These linkages will also be kept locked for only study staff to access. All endpoint devices storing these data are encrypted and protected with a strong password.

There are no other risks to study participation beyond the remote possibility of a breach of patient confidentiality, so no other human subjects’ protections are applicable to this proposal.

Requested Studies:

Study of Belatacept in Subjects Who Are Undergoing a Renal Transplant (BENEFIT-EXT)
Data Contributor: Bristol Myers Squibb
Study ID: NCT00114777
Sponsor ID: NCT00114777

Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT) (BENEFIT)
Data Contributor: Bristol Myers Squibb
Study ID: NCT00256750
Sponsor ID: NCT00256750

Public Disclosures:

Lange, N.W., King, K., Husain, S.A., Salerno, D.M., Tsapepas, D.S., Hedvat, J., Yu, M. and Mohan, S., 2024. Obesity is associated with a higher incidence of rejection in patients on belatacept: a pooled analysis from the BENEFIT/BENEFIT-EXT clinical trials. American Journal of Transplantation. Doi: 10.1016/j.ajt.2024.02.015