The 3C study is investigating whether reducing exposure to calcineurin inhibitors (by using more potent antibody induction treatment and/or an elective switch to sirolimus) can improve the function and survival of kidney transplants.
The long-term survival of kidney transplants has not improved over the past decade despite reductions in the rate of acute rejection. The commonest cause of late graft loss is chronic allograft nephropathy which is frequently caused by calcineurin inhibitor toxicity. Therefore, it may be possible to improve long-term graft outcomes by reducing the amount of calcineurin inhibitor exposure. Two possible strategies to do this were tested. Firstly, Campath-1H (a monoclonal lymphocyte-depleting antibody) was compared to standard basiliximab-based induction. All patients then received tacrolimus-based maintenance therapy for 6-months (using lower doses in the Campath-1H arm). At six months, patients were re-randomized between remaining on tacrolimus and converting to sirolimus (and therefore no longer taking calcineurin inhibitors). Patients were then followed-up in clinic and through routine NHS registries to collect information on relevant outcomes (including graft function, survival, hospitalisations and death).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
852
Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart
20 mg intravenously, two doses 96 hours apart
Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL
Oxford Radcliffe Hospitals NHS Trust
Oxford, Oxon, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy
Occurence of biopsy-proven acute rejection events at 6-months after transplantation during Period 1 (randomization to induction therapy (Campath-1H and Tacrolimus, or Basiliximab and Tacrolimus))
Time frame: 6 months post-transplantation
Graft Function (at 18-months After Randomization to Maintenance Therapy)
Estimated glomerular filtration rate (estimated using MDRD formula) at 18-months after maintenance therapy randomization to either Sirolimus or Tacrolimus.
Time frame: 2 years post-transplantation
Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy)
Return to dialysis or re-transplantation by 6-months after randomization to induction therapy.
Time frame: 6 months post-transplantation
Number of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy)
Return to dialysis or re-transplantation by 18-months after randomization to maintenance therapy.
Time frame: 2 years post-transplantation
Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy)
Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported within Period 1 (randomization to induction therapy of either Alemtuzumab (Campath-1H) and Tacrolimus, or Basiliximab and Tacrolimus).
Time frame: 6-months post-transplantation
Number of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy)
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Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.
Addenbrooke's Hospital NHS Trust
Cambridge, United Kingdom
University Hospital of Wales
Cardiff, United Kingdom
University Hospitals Coventry & Warwickshire
Coventry, United Kingdom
Royal Infirmary
Edinburgh, United Kingdom
Western Infirmary
Glasgow, United Kingdom
Hull and East Yorkshire Hospitals NHS Trust
Hull, United Kingdom
Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Liverpool, United Kingdom
...and 10 more locations
Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
Time frame: 2 years post-transplantation
Number of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy)
Occurrence of any cancer reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
Time frame: 2 years post-transplantation
Number of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy)
Composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization
Time frame: 2 years post-transplantation