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Trial record 1 of 1 for:    NCT01120028
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Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy (3C)

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ClinicalTrials.gov Identifier: NCT01120028
Recruitment Status : Active, not recruiting
First Posted : May 10, 2010
Results First Posted : October 1, 2019
Last Update Posted : October 1, 2019
Sponsor:
Collaborators:
National Health Service, United Kingdom
Pfizer
Novartis
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date  ICMJE May 6, 2010
First Posted Date  ICMJE May 10, 2010
Results First Submitted Date  ICMJE June 10, 2019
Results First Posted Date  ICMJE October 1, 2019
Last Update Posted Date October 1, 2019
Study Start Date  ICMJE September 2010
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2019)
  • Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy [ Time Frame: 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) [ Time Frame: 2 years post-transplantation ]
    Estimated glomerular filtration rate (estimated using MDRD formula) at 18-months after maintenance therapy randomization to either Sirolimus or Tacrolimus.
Original Primary Outcome Measures  ICMJE
 (submitted: May 6, 2010)
  • Biopsy-proven acute rejection [ Time Frame: 6 months ]
    Primary outcome for induction therapy comparison
  • Graft function [ Time Frame: 2 and 5 years post-transplantation ]
    Primary outcome for maintenance therapy comparison
Change History Complete list of historical versions of study NCT01120028 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2019)
  • Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy) [ Time Frame: 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) [ Time Frame: 2 years post-transplantation ]
    Return to dialysis or re-transplantation by 18-months after randomization to maintenance therapy.
  • Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy) [ Time Frame: 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) [ Time Frame: 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).
  • Number of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy) [ Time Frame: 2 years post-transplantation ]
    Occurrence of any cancer reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
  • Number of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy) [ Time Frame: 2 years post-transplantation ]
    Composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization
Original Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2010)
  • Graft survival [ Time Frame: 6 months, 2 and 5 years ]
  • Serious infection [ Time Frame: 2 and 5 years ]
  • Malignancy [ Time Frame: 2 and 5 years ]
  • Major vascular event [ Time Frame: 2 and 5 years ]
    Composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy
Official Title  ICMJE 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
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Kidney Transplantation
Intervention  ICMJE
  • Drug: Alemtuzumab
    Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart
    Other Name: Campath-1H
  • Drug: Basiliximab
    20 mg intravenously, two doses 96 hours apart
    Other Name: Simulect
  • Drug: Sirolimus
    Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL
    Other Name: Rapamune
  • Drug: Tacrolimus
    Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.
    Other Name: Prograf
Study Arms  ICMJE
  • Experimental: Alemtuzumab/Sirolimus

    Induction therapy allocation: Alemtuzumab (Campath-1H).

    Maintenance therapy allocation (at 6-months post-transplant): Sirolimus

    Interventions:
    • Drug: Alemtuzumab
    • Drug: Sirolimus
  • Experimental: Alemtuzumab/Tacrolimus

    Induction therapy allocation: Alemtuzumab (Campath-1H).

    Maintenance therapy allocation (at 6-months post-transplant): Tacrolimus

    Interventions:
    • Drug: Alemtuzumab
    • Drug: Tacrolimus
  • Active Comparator: Basiliximab/Tacrolimus

    Induction therapy allocation: Basiliximab.

    Maintenance therapy allocation (at 6-months post-transplant): Tacrolimus

    Interventions:
    • Drug: Basiliximab
    • Drug: Tacrolimus
  • Active Comparator: Basiliximab/Sirolimus

    Induction therapy allocation: Basiliximab.

    Maintenance therapy allocation (at 6-months post-transplant): Sirolimus

    Interventions:
    • Drug: Basiliximab
    • Drug: Sirolimus
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 26, 2019)
852
Original Estimated Enrollment  ICMJE
 (submitted: May 6, 2010)
800
Estimated Study Completion Date  ICMJE October 2019
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01120028
Other Study ID Numbers  ICMJE CTSU3C1
2008-008553-27 ( EudraCT Number )
ISRCTN88894088 ( Registry Identifier: ISRCTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Proposals for substudies must be approved by the Steering Committee. Procedure for accessing the data for this study are available on https://www.ndph.ox.ac.uk/data-access
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Access Criteria: See URL
URL: https://www.ndph.ox.ac.uk/data-access
Responsible Party University of Oxford
Study Sponsor  ICMJE University of Oxford
Collaborators  ICMJE
  • National Health Service, United Kingdom
  • Pfizer
  • Novartis
Investigators  ICMJE
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
PRS Account University of Oxford
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP