Clinical trial NCT01120028: Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Kidney Transplantation
Keywords: Kidney transplantation
Alemtuzumab
Sirolimus
Basiliximab
Tacrolimus
Campath-1H
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: National Health Service, United Kingdom
name: Pfizer
name: Novartis
First posted: 2010-05-10
Enrollment: 852
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy
timeFrame: 6 months post-transplantation
measure: Graft Function (at 18-months After Randomization to Maintenance Therapy)
timeFrame: 2 years post-transplantation
Secondary outcomes:
measure: Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy)
timeFrame: 6 months post-transplantation
measure: Number of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy)
timeFrame: 2 years post-transplantation
measure: Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy)
timeFrame: 6-months post-transplantation
measure: Number of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy)
timeFrame: 2 years post-transplantation
measure: Number of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy)
timeFrame: 2 years post-transplantation
measure: Number of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy)
timeFrame: 2 years post-transplantation
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospitals NHS Trust
state: Oxon
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital NHS Trust
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry & Warwickshire
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary
city: Glasgow
country: United Kingdom
facility: Western Infirmary
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire Hospitals NHS Trust
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: Royal Liverpool and Broadgreen University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Bart's and the London NHS Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas's NHS Trust
city: London
country: United Kingdom
facility: Kings College Hospital NHS Trust
city: London
country: United Kingdom
facility: Royal Free Hampstead NHS Trust
city: Manchester
country: United Kingdom
facility: Central Manchester NHS Trust
city: Newcastle
country: United Kingdom
facility: Newcastle-upon-Tyne Hospitals NHS Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: Plymouth Teaching Hospitals NHS Trust
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Trust
Study officials:
affiliation: University of Oxford
name: Peter Friend
role: STUDY_DIRECTOR
affiliation: University of Oxford
name: Colin Baigent
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oxford
name: Martin J Landray
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oxford
name: Paul Harden
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oxford
name: Richard Haynes
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.