Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy
- Conditions
- Kidney Transplantation
- Interventions
- Registration Number
- NCT01120028
- Lead Sponsor
- University of Oxford
- Brief Summary
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.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 852
- men or women aged over 18 years
- recipient of kidney transplant (planned in next 24 hours)
- recipients of multi-organ transplant
- previous treatment with Campath-1H
- active infection (including HIV, hepatitis B or C)
- history of anaphylaxis to humanized monoclonal antibody
- history of malignancy (except adequately treated non-melanoma skin cancer)
- loss of kidney transplant within 6 months not due to technical reasons
- medical history that might limit the individual's ability to take trial treatments for the duration of the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Basiliximab/Tacrolimus Tacrolimus Induction therapy allocation: Basiliximab. Maintenance therapy allocation (at 6-months post-transplant): Tacrolimus Alemtuzumab/Sirolimus Alemtuzumab Induction therapy allocation: Alemtuzumab (Campath-1H). Maintenance therapy allocation (at 6-months post-transplant): Sirolimus Alemtuzumab/Tacrolimus Tacrolimus Induction therapy allocation: Alemtuzumab (Campath-1H). Maintenance therapy allocation (at 6-months post-transplant): Tacrolimus Basiliximab/Sirolimus Sirolimus Induction therapy allocation: Basiliximab. Maintenance therapy allocation (at 6-months post-transplant): Sirolimus Basiliximab/Tacrolimus Basiliximab Induction therapy allocation: Basiliximab. Maintenance therapy allocation (at 6-months post-transplant): Tacrolimus Alemtuzumab/Sirolimus Sirolimus Induction therapy allocation: Alemtuzumab (Campath-1H). Maintenance therapy allocation (at 6-months post-transplant): Sirolimus Alemtuzumab/Tacrolimus Alemtuzumab Induction therapy allocation: Alemtuzumab (Campath-1H). Maintenance therapy allocation (at 6-months post-transplant): Tacrolimus Basiliximab/Sirolimus Basiliximab Induction therapy allocation: Basiliximab. Maintenance therapy allocation (at 6-months post-transplant): Sirolimus
- Primary Outcome Measures
Name Time Method Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy 6 months post-transplantation 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))
Graft Function (at 18-months After Randomization to Maintenance Therapy) 2 years post-transplantation Estimated glomerular filtration rate (estimated using MDRD formula) at 18-months after maintenance therapy randomization to either Sirolimus or Tacrolimus.
- Secondary Outcome Measures
Name Time Method Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy) 6 months post-transplantation Return to dialysis or re-transplantation by 6-months after randomization to induction therapy.
Number of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy) 2 years post-transplantation Return to dialysis or re-transplantation by 18-months after randomization to maintenance therapy.
Number of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy) 2 years post-transplantation Composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization
Number of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy) 2 years post-transplantation Occurrence of any cancer reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy) 6-months post-transplantation 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).
Number of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy) 2 years post-transplantation Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
Trial Locations
- Locations (20)
Oxford Radcliffe Hospitals NHS Trust
🇬🇧Oxford, Oxon, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
University Hospitals Coventry & Warwickshire
🇬🇧Coventry, United Kingdom
Kings College Hospital NHS Trust
🇬🇧London, United Kingdom
Central Manchester NHS Trust
🇬🇧Manchester, United Kingdom
Newcastle-upon-Tyne Hospitals NHS Trust
🇬🇧Newcastle, United Kingdom
Hull and East Yorkshire Hospitals NHS Trust
🇬🇧Hull, United Kingdom
Royal Infirmary
🇬🇧Edinburgh, United Kingdom
Royal Liverpool and Broadgreen University Hospitals NHS Trust
🇬🇧Liverpool, United Kingdom
Western Infirmary
🇬🇧Glasgow, United Kingdom
Sheffield Teaching Hospitals NHS Trust
🇬🇧Sheffield, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Addenbrooke's Hospital NHS Trust
🇬🇧Cambridge, United Kingdom
Guy's and St Thomas's NHS Trust
🇬🇧London, United Kingdom
Bart's and the London NHS Trust
🇬🇧London, United Kingdom
Plymouth Teaching Hospitals NHS Trust
🇬🇧Plymouth, United Kingdom
Royal Free Hampstead NHS Trust
🇬🇧London, United Kingdom
Portsmouth Hospitals NHS Trust
🇬🇧Portsmouth, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom