Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy (3C)
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| ClinicalTrials.gov Identifier: NCT01120028 |
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Recruitment Status :
Completed
First Posted : May 10, 2010
Results First Posted : October 1, 2019
Last Update Posted : April 2, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Kidney Transplantation | Drug: Alemtuzumab Drug: Basiliximab Drug: Sirolimus Drug: Tacrolimus | Phase 2 Phase 3 |
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 (Clinical Trial) |
| Actual Enrollment : | 852 participants |
| Allocation: | Randomized |
| Intervention Model: | Factorial Assignment |
| Masking: | None (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 |
| Actual Study Start Date : | September 2010 |
| Actual Primary Completion Date : | February 2014 |
| Actual Study Completion Date : | March 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Alemtuzumab/Sirolimus
Induction therapy allocation: Alemtuzumab (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 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL
Other Name: Rapamune |
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Experimental: Alemtuzumab/Tacrolimus
Induction therapy allocation: Alemtuzumab (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 Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.
Other Name: Prograf |
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Active Comparator: Basiliximab/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 Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.
Other Name: Prograf |
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Active Comparator: Basiliximab/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 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL
Other Name: Rapamune |
- 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.
- 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
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01120028
Show 20 study locations
| 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 |
Documents provided by University of Oxford:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | University of Oxford |
| ClinicalTrials.gov Identifier: | NCT01120028 |
| Other Study ID Numbers: |
CTSU3C1 2008-008553-27 ( EudraCT Number ) ISRCTN88894088 ( Registry Identifier: ISRCTN ) |
| First Posted: | May 10, 2010 Key Record Dates |
| Results First Posted: | October 1, 2019 |
| Last Update Posted: | April 2, 2020 |
| Last Verified: | March 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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 Statistical Analysis Plan (SAP) |
| Access Criteria: | See URL |
| URL: | https://www.ndph.ox.ac.uk/data-access |
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Kidney transplantation Alemtuzumab Sirolimus |
Basiliximab Tacrolimus Campath-1H |
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Sirolimus Alemtuzumab Tacrolimus Basiliximab Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Calcineurin Inhibitors |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antineoplastic Agents Antifungal Agents Antineoplastic Agents, Immunological |