{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T13:56:56Z","timestamp":1766671016084,"version":"3.48.0"},"reference-count":35,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"unspecified","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIHR Research for Patient Benefit","award":["PB-PG-0815-20061"],"award-info":[{"award-number":["PB-PG-0815-20061"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,11,24]]},"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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\u2019s lymphoma (NHL) receiving anthracycline-based chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>A favourable opinion was given following research ethics committee review by West Midlands\u2014Edgbaston 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03265574\">NCT03265574<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-066252","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T10:11:49Z","timestamp":1672395109000},"page":"e066252","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Preventing cardiotoxicity in patients with breast cancer and lymphoma: protocol for a multicentre randomised controlled trial (PROACT)"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct03265574","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"isrctn24439460","registry":"10.18810\/isrctn"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7350-3288","authenticated-orcid":false,"given":"Rebecca H","family":"Maier","sequence":"first","affiliation":[{"name":"Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK"},{"name":"South Tees Hospitals NHS Foundation Trust, Academic Cardiovascular Unit, South Tees, Middlesbrough, UK"},{"name":"Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Plummer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0411-3059","authenticated-orcid":false,"given":"Adetayo S","family":"Kasim","sequence":"additional","affiliation":[{"name":"Department of Anthropology, Durham University, Durham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-1593","authenticated-orcid":false,"given":"Nasima","family":"Akhter","sequence":"additional","affiliation":[{"name":"Department of Anthropology, Durham University, Durham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Ogundimu","sequence":"additional","affiliation":[{"name":"Mathematical Sciences, University of Durham, Durham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7995-7934","authenticated-orcid":false,"given":"Jamie","family":"Maddox","sequence":"additional","affiliation":[{"name":"Department of Haematology, South Tees Hospitals NHS Foundation Trust, Middlesborough, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Oncology, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Cardiology, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Wardley","sequence":"additional","affiliation":[{"name":"Outreach Research & Innovation Group, Didsbury, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Haney","sequence":"additional","affiliation":[{"name":"Department of Oncology, County Durham and Darlington NHS Foundation Trust, Darlington, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharareh","family":"Vahabi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Oxenham","sequence":"additional","affiliation":[{"name":"Department of Cardiology, North Tees and Hartlepool NHS Foundation Trust, Hartlepool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Humphreys","sequence":"additional","affiliation":[{"name":"Department of Oncology, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0495-4472","authenticated-orcid":false,"given":"Nicola","family":"Cresti","sequence":"additional","affiliation":[{"name":"Department of Oncology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Verrill","sequence":"additional","affiliation":[{"name":"Department of Oncology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Cardiology, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Chang","sequence":"additional","affiliation":[{"name":"South Tees Hospitals NHS Foundation Trust, Academic Cardiovascular Unit, South Tees, Middlesbrough, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1494-8551","authenticated-orcid":false,"given":"Helen C","family":"Hancock","sequence":"additional","affiliation":[{"name":"Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4606-1055","authenticated-orcid":false,"given":"David","family":"Austin","sequence":"additional","affiliation":[{"name":"South Tees Hospitals NHS Foundation Trust, Academic Cardiovascular Unit, South Tees, Middlesbrough, UK"},{"name":"Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Department of Cardiology, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"2025121410453020000_12.12.e066252.1","unstructured":"Cancer Research UK . Breast cancer statistics. Available: http:\/\/www.cancerresearchuk.org\/health-professional\/cancer-statistics\/statistics-by-cancer-type\/breast-cancer [Accessed 26 Apr 2022]."},{"key":"2025121410453020000_12.12.e066252.2","unstructured":"World Cancer Research Fund International . Breast cancer statistics. Available: https:\/\/www.wcrf.org\/cancer-trends\/breast-cancer-statistics\/ [Accessed 26 Apr 2022]."},{"key":"2025121410453020000_12.12.e066252.3","unstructured":"Cancer research UK non-Hodgkin lymphoma statistics. Available: https:\/\/www.cancerresearchuk.org\/health-professional\/cancer-statistics\/statistics-by-cancer-type\/non-hodgkin-lymphoma [Accessed 26 Apr 2022]."},{"key":"2025121410453020000_12.12.e066252.4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.016704"},{"key":"2025121410453020000_12.12.e066252.5","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11407"},{"key":"2025121410453020000_12.12.e066252.6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.10.4976"},{"key":"2025121410453020000_12.12.e066252.7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1991.03470120074036"},{"key":"2025121410453020000_12.12.e066252.8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013777"},{"key":"2025121410453020000_12.12.e066252.9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052306"},{"key":"2025121410453020000_12.12.e066252.10","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.65"},{"key":"2025121410453020000_12.12.e066252.11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200004133421502"},{"key":"2025121410453020000_12.12.e066252.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61396-9"},{"key":"2025121410453020000_12.12.e066252.13","doi-asserted-by":"publisher","DOI":"10.1161\/hc3801.095585"},{"key":"2025121410453020000_12.12.e066252.14","first-page":"4766","article-title":"Adriamycin-induced free radical formation in the perfused rat heart: implications for cardiotoxicity","volume":"48","author":"Rajagopalan","year":"1988","journal-title":"Cancer Res"},{"key":"2025121410453020000_12.12.e066252.15","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-9842(02)00091-0"},{"key":"2025121410453020000_12.12.e066252.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2009.01.001"},{"key":"2025121410453020000_12.12.e066252.17","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e318258f8ce"},{"key":"2025121410453020000_12.12.e066252.18","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200969030-00003"},{"key":"2025121410453020000_12.12.e066252.19","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/01.fjc.0000175234.95831.3e","article-title":"Perindopril regulates beta-agonist-induced cardiac apoptosis","volume":"46","author":"G\u00e1lvez","year":"2005","journal-title":"J Cardiovasc Pharmacol"},{"key":"2025121410453020000_12.12.e066252.20","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409077"},{"key":"2025121410453020000_12.12.e066252.21","unstructured":"British National formulary. Available: https:\/\/www.evidence.nhs.uk\/formulary\/bnf\/current [Accessed 28 Nov 2015]."},{"key":"2025121410453020000_12.12.e066252.22","first-page":"CD003917","article-title":"Cardioprotective interventions for cancer patients receiving anthracyclines","volume":"2011","author":"van Dalen","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"2025121410453020000_12.12.e066252.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.04.030"},{"key":"2025121410453020000_12.12.e066252.24","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1407-6"},{"key":"2025121410453020000_12.12.e066252.25","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw211"},{"key":"2025121410453020000_12.12.e066252.26","doi-asserted-by":"crossref","first-page":"4229","DOI":"10.1093\/eurheartj\/ehac244","article-title":"2022 ESC guidelines on cardio-oncology developed in collaboration with the European hematology association (EHA) the European Society for therapeutic radiology and oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS): developed by the task force on cardio-oncology of the European Society of cardiology (ESC)","volume":"43","author":"Lyon","year":"2022","journal-title":"Eur Heart J"},{"key":"2025121410453020000_12.12.e066252.27","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000130926.51766.CC"},{"key":"2025121410453020000_12.12.e066252.28","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw022"},{"key":"2025121410453020000_12.12.e066252.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.02.072"},{"key":"2025121410453020000_12.12.e066252.30","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1161\/CIRCULATIONAHA.121.054698","article-title":"Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): extended follow-up of a 2\u00d72 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol","volume":"143","author":"Heck","year":"2021","journal-title":"Circulation"},{"key":"2025121410453020000_12.12.e066252.31","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ejca.2018.02.005","article-title":"Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial","volume":"94","author":"Cardinale","year":"2018","journal-title":"Eur J Cancer"},{"key":"2025121410453020000_12.12.e066252.32","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1002\/ehf2.12695","article-title":"Circulating biomarkers and cardiac function over 3 years after chemotherapy with anthracyclines: the ICOS-ONE trial","volume":"7","author":"Meessen","year":"2020","journal-title":"ESC Heart Fail"},{"key":"2025121410453020000_12.12.e066252.33","unstructured":"Cardiac care the cardiac care trial. Available: http:\/\/www.isrctn.com\/ISRCTN24439460 [Accessed 26 Apr 2022]."},{"key":"2025121410453020000_12.12.e066252.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00748-8"},{"key":"2025121410453020000_12.12.e066252.35","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000130926.51766.CC"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2022-066252","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T18:45:37Z","timestamp":1765737937000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2022-066252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12,30]]},"published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1136\/bmjopen-2022-066252"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2022-066252","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2022,12]]}}}