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Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy (3C)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Health Service, United Kingdom
Pfizer
Novartis
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01120028
First received: May 6, 2010
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

The 3C study will investigate 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.


Condition Intervention Phase
Kidney Transplantation
Drug: Alemtuzumab
Drug: Basiliximab
Drug: Sirolimus
Drug: Tacrolimus
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Randomised Multicentre Study of CAMPATH-1H Versus Basiliximab Induction Treatment and Sirolimus Versus Tacrolimus Maintenance Treatment for the Preservation of Renal Function in Patients Receiving Kidney Transplants

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Biopsy-proven acute rejection [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Primary outcome for induction therapy comparison

  • Graft function [ Time Frame: 2 and 5 years post-transplantation ] [ Designated as safety issue: No ]
    Primary outcome for maintenance therapy comparison


Secondary Outcome Measures:
  • Graft survival [ Time Frame: 6 months, 2 and 5 years ] [ Designated as safety issue: No ]
  • Serious infection [ Time Frame: 2 and 5 years ] [ Designated as safety issue: Yes ]
  • Malignancy [ Time Frame: 2 and 5 years ] [ Designated as safety issue: Yes ]
  • Major vascular event [ Time Frame: 2 and 5 years ] [ Designated as safety issue: No ]
    Composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization


Estimated Enrollment: 800
Study Start Date: September 2010
Estimated Study Completion Date: February 2017
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Campath-1H/Sirolimus
Induction therapy allocation: Campath-1H Maintenance therapy allocation (at 6 months post-transplant): Sirolimus
Drug: Alemtuzumab
Alemtuzumab 30 mg intravenously or subcutaneously Two doses 24 hours apart
Other Name: Campath-1H
Drug: Sirolimus
Sirolimus: target trough levels 5-10 ng/mL for first 6 months, then 5-8 ng/mL
Other Name: Rapamune
Experimental: Campath-1H/Tacrolimus
Induction therapy allocation: Campath-1H Maintenance therapy allocation (at 6 months post-transplant): Tacrolimus
Drug: Alemtuzumab
Alemtuzumab 30 mg intravenously or subcutaneously Two doses 24 hours apart
Other Name: Campath-1H
Drug: Tacrolimus
Target trough level 5-12 ng/mL for first 6 months after basiliximab; 5-7 ng/mL for first six months after basiliximab. 5-7 ng/mL for all participants after 6 months.
Other Name: Prograf
Active Comparator: Basliximab/Tacrolimus
Induction therapy allocation: Basiliximab Maintenance therapy allocation (at 6 months post-transplant): Tacrolimus
Drug: Basiliximab
20 mg intravenously Two doses 96 hours apart
Other Name: Simulect
Drug: Tacrolimus
Target trough level 5-12 ng/mL for first 6 months after basiliximab; 5-7 ng/mL for first six months after basiliximab. 5-7 ng/mL for all participants after 6 months.
Other Name: Prograf
Active Comparator: Basliximab/Sirolimus
Induction therapy allocation: Basiliximab Maintenance therapy allocation (at 6 months post-transplant): Sirolimus
Drug: Basiliximab
20 mg intravenously Two doses 96 hours apart
Other Name: Simulect
Drug: Sirolimus
Sirolimus: target trough levels 5-10 ng/mL for first 6 months, then 5-8 ng/mL
Other Name: Rapamune

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 will be tested. Firstly, Campath-1H (a monoclonal lymphocyte-depleting antibody) will be compared to standard basiliximab-based induction. All patients will then receive tacrolimus-based maintenance therapy for 6 months (using lower doses in the Campath-1H arm).

At six months, patients will be re-randomised between remaining on tacrolimus and converting to sirolimus (and therefore no longer take calcineurin inhibitors). Patients will then be followed-up in clinic and through routine NHS registries to collect information on relevant outcomes (including graft function, survival, hospitalisations and death).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • men or women aged over 18 years
  • recipient of kidney transplant (planned in next 24 hours)

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01120028

Locations
United Kingdom
Oxford Radcliffe Hospitals NHS Trust
Oxford, Oxon, United Kingdom, OX3 7LJ
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
Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Liverpool, United Kingdom
Bart's and the London NHS Trust
London, United Kingdom
Guy's and St Thomas's NHS Trust
London, United Kingdom
Central Manchester NHS Trust
Manchester, United Kingdom
Newcastle-upon-Tyne Hospitals NHS Trust
Newcastle, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Plymouth Teaching Hospitals NHS Trust
Plymouth, United Kingdom
Portsmouth Hospitals NHS Trust
Portsmouth, United Kingdom
Sheffield Teaching Hospitals NHS Trust
Sheffield, United Kingdom
Sponsors and Collaborators
University of Oxford
National Health Service, United Kingdom
Pfizer
Novartis
Investigators
Study Director: Peter Friend University of Oxford
Principal Investigator: Colin Baigent University of Oxford
Principal Investigator: Martin J Landray University of Oxford
Principal Investigator: Paul Harden University of Oxford
Principal Investigator: Richard Haynes University of Oxford
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01120028     History of Changes
Other Study ID Numbers: CTSU3C1, 2008-008553-27, ISRCTN88894088
Study First Received: May 6, 2010
Last Updated: April 16, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Alemtuzumab
Basiliximab
Everolimus
Sirolimus
Tacrolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014