Campath, calcineurin inhibitor reduction, and chronic allograft nephropathy (the 3C Study) - results of a randomized controlled clinical trial

Am J Transplant. 2018 Jun;18(6):1424-1434. doi: 10.1111/ajt.14619. Epub 2018 Jan 9.


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 m2 in the sirolimus group versus 54.6 (0.9) mL/min/1.73 m2 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. identifier NCT01120028 and ISRCTN88894088.

Keywords: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alemtuzumab / pharmacology*
  • Calcineurin Inhibitors / adverse effects*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / physiopathology
  • Male
  • Middle Aged
  • Transplantation, Homologous / adverse effects*


  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Alemtuzumab

Associated data

  • ISRCTN/ISRCTN88894088