Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy

NCT ID: NCT01120028

Last Updated: 2020-04-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

852 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-09-30

Study Completion Date

2020-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Kidney Transplantation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Alemtuzumab/Sirolimus

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

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

Group Type EXPERIMENTAL

Alemtuzumab

Intervention Type DRUG

Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart

Sirolimus

Intervention Type DRUG

Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL

Alemtuzumab/Tacrolimus

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

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

Group Type EXPERIMENTAL

Alemtuzumab

Intervention Type DRUG

Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart

Tacrolimus

Intervention Type DRUG

Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.

Basiliximab/Tacrolimus

Induction therapy allocation: Basiliximab.

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

Group Type ACTIVE_COMPARATOR

Basiliximab

Intervention Type DRUG

20 mg intravenously, two doses 96 hours apart

Tacrolimus

Intervention Type DRUG

Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.

Basiliximab/Sirolimus

Induction therapy allocation: Basiliximab.

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

Group Type ACTIVE_COMPARATOR

Basiliximab

Intervention Type DRUG

20 mg intravenously, two doses 96 hours apart

Sirolimus

Intervention Type DRUG

Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Alemtuzumab

Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart

Intervention Type DRUG

Basiliximab

20 mg intravenously, two doses 96 hours apart

Intervention Type DRUG

Sirolimus

Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL

Intervention Type DRUG

Tacrolimus

Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Campath-1H Simulect Rapamune Prograf

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Health Service, United Kingdom

OTHER_GOV

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role collaborator

Novartis

INDUSTRY

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Peter Friend

Role: STUDY_DIRECTOR

University of Oxford

Colin Baigent

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Martin J Landray

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Paul Harden

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Richard Haynes

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Oxford Radcliffe Hospitals NHS Trust

Oxford, Oxon, United Kingdom

Site Status

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

Addenbrooke's Hospital NHS Trust

Cambridge, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

University Hospitals Coventry & Warwickshire

Coventry, , United Kingdom

Site Status

Royal Infirmary

Edinburgh, , United Kingdom

Site Status

Western Infirmary

Glasgow, , United Kingdom

Site Status

Hull and East Yorkshire Hospitals NHS Trust

Hull, , United Kingdom

Site Status

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Site Status

Royal Liverpool and Broadgreen University Hospitals NHS Trust

Liverpool, , United Kingdom

Site Status

Bart's and the London NHS Trust

London, , United Kingdom

Site Status

Guy's and St Thomas's NHS Trust

London, , United Kingdom

Site Status

Kings College Hospital NHS Trust

London, , United Kingdom

Site Status

Royal Free Hampstead NHS Trust

London, , United Kingdom

Site Status

Central Manchester NHS Trust

Manchester, , United Kingdom

Site Status

Newcastle-upon-Tyne Hospitals NHS Trust

Newcastle, , United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status

Plymouth Teaching Hospitals NHS Trust

Plymouth, , United Kingdom

Site Status

Portsmouth Hospitals NHS Trust

Portsmouth, , United Kingdom

Site Status

Sheffield Teaching Hospitals NHS Trust

Sheffield, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

3C Study Collaborative Group; Haynes R, Harden P, Judge P, Blackwell L, Emberson J, Landray MJ, Baigent C, Friend PJ. Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet. 2014 Nov 8;384(9955):1684-90. doi: 10.1016/S0140-6736(14)61095-3. Epub 2014 Jul 28.

Reference Type RESULT
PMID: 25078310 (View on PubMed)

3C Study Collaborative Group. Campath, calcineurin inhibitor reduction, and chronic allograft nephropathy (the 3C Study) - results of a randomized controlled clinical trial. Am J Transplant. 2018 Jun;18(6):1424-1434. doi: 10.1111/ajt.14619. Epub 2018 Jan 9.

Reference Type RESULT
PMID: 29226570 (View on PubMed)

Haynes R, Baigent C, Harden P, Landray M, Akyol M, Asderakis A, Baxter A, Bhandari S, Chowdhury P, Clancy M, Emberson J, Gibbs P, Hammad A, Herrington W, Jayne K, Jones G, Krishnan N, Lay M, Lewis D, Macdougall I, Nathan C, Neuberger J, Newstead C, Pararajasingam R, Puliatti C, Rigg K, Rowe P, Sharif A, Sheerin N, Sinha S, Watson C, Friend P; 3C Study Collaborative Group. Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol. Transplant Res. 2013 May 6;2(1):7. doi: 10.1186/2047-1440-2-7.

Reference Type DERIVED
PMID: 23641902 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Statistical Analysis Plan: Induction Therapy Data Analysis Plan

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Maintenance Therapy Data Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

http://www.3cstudy.org/

3C study website

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2008-008553-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN88894088

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTSU3C1

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Calcineurin Activity in Renal Recipients
NCT01413685 TERMINATED PHASE4