Preventing cardiotoxicity in patients with breast cancer and lymphoma: protocol for a multicentre randomised controlled trial (PROACT)

Maier, Rebecca H; Plummer, Chris; Kasim, Adetayo S; Akhter, Nasima; Ogundimu, Emmanuel; Maddox, Jamie; Graham, Janine; Stewart, Michael; Wardley, Andrew; Haney, Sophie; Vahabi, Sharareh; Oxenham, Helen; Humphreys, Alison; Cresti, Nicola; Verrill, Mark; Graham, Richard; Chang, Lisa; Hancock, Helen C; Austin, David

doi:10.1136/bmjopen-2022-066252

Preventing cardiotoxicity in patients with breast cancer and lymphoma: protocol for a multicentre randomised controlled trial (PROACT)

Maier, Rebecca H; Plummer, Chris; Kasim, Adetayo S; Akhter, Nasima; Ogundimu, Emmanuel; Maddox, Jamie; Graham, Janine; Stewart, Michael; Wardley, Andrew; Haney, Sophie; Vahabi, Sharareh; Oxenham, Helen; Humphreys, Alison; Cresti, Nicola; Verrill, Mark; Graham, Richard; Chang, Lisa; Hancock, Helen C; Austin, David

Authors

Rebecca H Maier

Chris Plummer

Adetayo S Kasim

Dr Nasima Akhter nasima.akhter@durham.ac.uk
Assistant Professor

Emmanuel Ogundimu

Jamie Maddox

Janine Graham

Michael Stewart

Andrew Wardley

Sophie Haney

Sharareh Vahabi

Helen Oxenham

Alison Humphreys

Nicola Cresti

Mark Verrill

Richard Graham

Lisa Chang

Helen C Hancock

David Austin

Abstract

Introduction: Anthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can cause irreversible damage to cardiac cells and ultimately impaired cardiac function and heart failure, which may only be evident years after exposure. The PROACT trial will establish the effectiveness of the ACE inhibitor enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin’s lymphoma (NHL) receiving anthracycline-based chemotherapy. Methods and analysis: PROACT is a prospective, randomised, open-label, blinded end-point, superiority trial which will recruit adult patients being treated for breast cancer and NHL at NHS hospitals throughout England. The trial aims to recruit 106 participants, who will be randomised to standard care (high-dose anthracycline-based chemotherapy) plus enalapril (intervention) or standard care alone (control). Patients randomised to the intervention arm will receive enalapril (starting at 2.5 mg two times per day and titrating up to a maximum dose of 10 mg two times per day), commencing treatment at least 2 days prior to starting chemotherapy and finishing 3 weeks after their last anthracycline dose. The primary outcome is the presence or absence of cardiac troponin T release at any time during anthracycline treatment, and 1 month after the last dose of anthracycline. Secondary outcomes will focus on cardiac function measured using echocardiogram assessment, adherence to enalapril and side effects. Ethics and dissemination: A favourable opinion was given following research ethics committee review by West Midlands—Edgbaston REC, Ref: 17/WM/0248. Trial findings will be disseminated through engagement with patients, the oncology and cardiology communities, NHS management and commissioning groups and through peer-reviewed publication.

Citation

Maier, R. H., Plummer, C., Kasim, A. S., Akhter, N., Ogundimu, E., Maddox, J., …Austin, D. (2022). Preventing cardiotoxicity in patients with breast cancer and lymphoma: protocol for a multicentre randomised controlled trial (PROACT). BMJ Open, 12(12), Article e066252. https://doi.org/10.1136/bmjopen-2022-066252

Journal Article Type	Article
Acceptance Date	Nov 24, 2022
Online Publication Date	Dec 30, 2022
Publication Date	2022-12
Deposit Date	Jan 6, 2023
Publicly Available Date	Jan 6, 2023
Journal	BMJ Open
Electronic ISSN	2044-6055
Publisher	BMJ Publishing Group
Peer Reviewed	Peer Reviewed
Volume	12
Issue	12
Article Number	e066252
DOI	https://doi.org/10.1136/bmjopen-2022-066252
Public URL	https://durham-repository.worktribe.com/output/1184005

Files

Published Journal Article (1.3 Mb)
PDF

Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.