Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial.

3C Study Collaborative Group and Asderakis, Argiris ORCID: https://orcid.org/0000-0001-6859-2020 2014. Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet (London, England) 384 (9955) , pp. 1684-1690. 10.1016/s0140-6736(14)61095-3

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Abstract

Background: Calcineurin inhibitors (CNIs) reduce short-term kidney transplant failure, but might contribute to transplant failure in the long-term. The role of alemtuzumab (a potent lymphocyte-depleting antibody) as an induction treatment followed by an early reduction in CNI and mycophenolate exposure and steroid avoidance, after kidney transplantation is uncertain. We aimed to assess the efficacy and safety of alemtuzumab-based induction treatment compared with basiliximab-based induction treatment in patients receiving kidney transplants. Methods: For this randomised trial, we enrolled patients aged 18 years and older who were scheduled to receive a kidney transplant in the next 24 h from 18 transplant centres in the UK. Using minimised randomisation, we randomly assigned patients (1:1; minimised for age, sex, and immunological risk) to either alemtuzumab-based induction treatment (ie, alemtuzumab followed by low-dose tacrolimus and mycophenolate without steroids) or basiliximab-based induction treatment (basiliximab followed by standard-dose tacrolimus, mycophenolate, and prednisolone). Participants were reviewed at discharge from hospital and at 1, 3, 6, 9, and 12 months after transplantation. The primary outcome was biopsy-proven acute rejection at 6 months, analysed by intention to treat. The study is registered at ClinicalTrials.gov, number NCT01120028, and isrctn.org, number ISRCTN88894088. Findings: Between Oct 4, 2010, and Jan 21, 2013, we randomly assigned 852 participants to treatment: 426 to alemtuzumab-based treatment and 426 to basiliximab-based treatment. Overall, individuals allocated to alemtuzumab-based treatment had a 58% proportional reduction in biopsy-proven acute rejection compared with those allocated to basiliximab-based treatment (31 [7%] patients in the alemtuzumab group vs 68 [16%] patients in the basiliximab group; hazard ratio (HR) 0·42, 95% CI 0·28-0·64; log-rank p<0·0001). We detected no between-group difference in treatment effect on transplant failure during the first 6 months (16 [4%] patients vs 13 [3%] patients; HR 1·23, 0·59-2·55; p=0·58) or serious infection (135 [32%] patients vs 136 [32%] patients; HR 1·02, 0·80-1·29; p=0·88). During the first 6 months after transplantation, 11 (3%) patients given alemtuzumab-based treatment and six (1%) patients given basiliximab-based treatment died (HR 1·79, 95% CI 0·66-4·83; p=0·25). Interpretation: Compared with standard basiliximab-based treatment, alemtuzumab-based induction therapy followed by reduced CNI and mycophenolate exposure and steroid avoidance reduced the risk of biopsy-proven acute rejection in a broad range of patients receiving a kidney transplant. Long-term follow-up of this trial will assess whether these effects translate into differences in long-term transplant function and survival.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	Argiris Asderakis - Member of the steering committee Writing committee Richard Haynes, Paul Harden, Parminder Judge, Lisa Blackwell, Jonathan Emberson, Martin J Landray, Prof Colin Baigent, Prof Peter J Friend. Steering Committee Chair: Prof Peter J Friend (co-principal investigator; CPI). Members: Richard Haynes (Clinical Coordinator; CPI), Prof Colin Baigent (CPI), Paul Harden (CPI), Martin J Landray (CPI), Murat Akyol, Argiris Asderakis, Alex Baxter, Prof Sunil Bhandari, Paramit Chowdhury, Marc Clancy, Paul Gibbs, Abdulqader Hammad, William Herrington, Kathy Jayne, Gareth Jones, Nithya Krishnan, Michael Lay, David Lewis, Prof Iain C Macdougall, V Chidambaram Nathan, Prof James Neuberger, Charles Newstead, Ravi Pararajasingam, Carmelo Puliatti, Keith Rigg, Peter Rowe, Adnan Sharif, Prof Neil Sheerin, Sanjay Sinha, Nicholas Torpey, Prof Christopher J E Watson. Data monitoring committee Chair: Prof Sir Peter Morris. Members: Prof Keith Wheatley, Prof Daniel Abramowicz; Non-voting statisticians Jonathan Emberson, Lisa Blackwell.
ISSN:	0140-6736
Last Modified:	10 Nov 2022 11:28
URI:	https://orca.cardiff.ac.uk/id/eprint/150665

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