Campath, calcineurin inhibitor reduction, and chronic allograft nephropathy (the 3C Study) – results of a randomized controlled clinical trial. Issue 6 (9th January 2018)

• Record Type: Journal Article
• Other Names: Haynes Richard investigator.; Blackwell Lisa investigator.; Staplin Natalie investigator.; Herrington William G. investigator.; Emberson Jonathan investigator.; Judge Parminder K. investigator.; Storey Benjamin C. investigator.; Landray Martin J. investigator.; Harden Paul N. investigator.; Baigent Colin investigator.; Friend Peter investigator.
• Is Part Of: American journal of transplantation. Volume 18:Issue 6(2018)
• Page Start: 1424
• Page End: 1434
• Publication Date: 2018-01-09
• Subjects: clinical research/practice -- immunosuppressant ‐ calcineurin inhibitor (CNI) -- immunosuppressant ‐ fusion proteins and monoclonal antibodies: alemtuzumab -- immunosuppressant ‐ fusion proteins and monoclonal antibodies: basiliximab/daclizumab -- immunosuppressant ‐ mechanistic target of rapamycin (mTOR) -- immunosuppression/immune modulation -- kidney transplantation/nephrology; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.14619
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Calcineurin inhibitors (CNIs, eg, tacrolimus) reduce short‐term kidney transplant failure, but chronic nephrotoxicity may contribute to late transplant loss. Elective conversion to inhibitors of the mammalian target of rapamycin (mTOR, eg, sirolimus) pathway might avoid long‐term CNI renal damage and improve outcomes. The 3C Study was a pragmatic randomized controlled trial of sequential randomizations between alemtuzumab and basiliximab induction therapy (at the time of surgery) and between tacrolimus and sirolimus maintenance therapy at 6 months posttransplantation. The primary outcome of this analysis was estimated glomerular filtration rate (eGFR) at 18 months after maintenance therapy randomization; 197 patients were assigned sirolimus‐based and 197 to tacrolimus‐based therapy. Allocation to sirolimus had no significant effect on eGFR at 18 months: baseline‐adjusted mean (SEM) eGFR was 53.7 (0.9) mL/min/1.73 m 2 in the sirolimus group versus 54.6 (0.9) mL/min/1.73 m 2 in the tacrolimus group ( P = .50). Biopsy‐proven acute rejection (29 [14.7%]) vs 6 [3.0%]; P < .001) and serious infections (defined as opportunistic infections or those requiring hospitalization; 95 [48.2%] vs 70 [35.5%]; P = .008) were more common among participants allocated sirolimus. Compared with tacrolimus‐based therapy, sirolimus‐based maintenance therapy did not improve transplant function at 18 months after conversion and was associated with significant hazards of rejection and infection. ClinicalTrials.gov identifier NCT01120028 and ISRCTN88894088. Abstract : The 3C Study tested whether elective conversion to sirolimus‐based maintenance therapy was better than continued tacrolimus‐based maintenance therapy at 6 months after kidney transplantation and finds no improvement in transplant function, but increased risks of transplant rejection and infection with sirolimus.