title: Effect of Remote Ischaemic Conditioning in Oncology Patients Undergoing Chemotherapy: Rationale and Design of the ERIC-ONC Study--A Single-Center, Blinded, Randomized Controlled Trial.
abstract: Cancer survival continues to improve, and thus cardiovascular consequences of chemotherapy are increasingly important determinants of long-term morbidity and mortality. Conventional strategies to protect the heart from chemotherapy have important hemodynamic or myelosuppressive side effects. Remote ischemic conditioning (RIC) using intermittent limb ischemia-reperfusion reduces myocardial injury in the setting of percutaneous coronary intervention. Anthracycline cardiotoxicity and ischemia-reperfusion injury share common biochemical pathways in cardiomyocytes. The potential for RIC as a novel treatment to reduce subclinical myocyte injury in chemotherapy has never been explored and will be investigated in the Effect of Remote Ischaemic Conditioning in Oncology (ERIC-ONC) trial (clinicaltrials.gov NCT 02471885). The ERIC-ONC trial is a single-center, blinded, randomized, sham-controlled study. We aim to recruit 128 adult oncology patients undergoing anthracycline-based chemotherapy treatment, randomized in a 1:1 ratio into 2 groups: (1) sham procedure or (2) RIC, comprising 4, 5-minute cycles of upper arm blood pressure cuff inflations and deflations, immediately before each cycle of chemotherapy. The primary outcome measure, defining cardiac injury, will be high-sensitivity troponin-T over 6 cycles of chemotherapy and 12 months follow-up. Secondary outcome measures will include clinical, electrical, structural, and biochemical endpoints comprising major adverse cardiovascular clinical events, incidence of cardiac arrhythmia over 14 days at cycle 5/6, echocardiographic ventricular function, N-terminal pro-brain natriuretic peptide levels at 3 months follow-up, and changes in mitochondrial DNA, micro-RNA, and proteomics after chemotherapy. The ERIC-ONC trial will determine the efficacy of RIC as a novel, noninvasive, nonpharmacological, low-cost cardioprotectant in cancer patients undergoing anthracycline-based chemotherapy.
authors.affiliation: The Hatter Cardiovascular Institute, University College London, London, United Kingdom.
authors.forename: Robin
authors.initials: R
authors.lastname: Chung
authors.affiliation: The Hatter Cardiovascular Institute, University College London, London, United Kingdom.
authors.forename: Angshuman
authors.initials: A
authors.lastname: Maulik
authors.affiliation: The Hatter Cardiovascular Institute, University College London, London, United Kingdom.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Hamarneh
authors.affiliation: Research Department of Oncology, The Cancer Institute, University College London, London, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hochhauser
authors.affiliation: The Hatter Cardiovascular Institute, University College London, London, United Kingdom.|Cardiovascular and Metabolic Disorders Program, Duke University-National University of Singapore Medical School, Singapore.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Hausenloy
authors.affiliation: The Hatter Cardiovascular Institute, University College London, London, United Kingdom.
authors.forename: J Malcolm
authors.initials: JM
authors.lastname: Walker
authors.affiliation: The Hatter Cardiovascular Institute, University College London, London, United Kingdom.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Yellon
mesh_terms: D018943:Anthracyclines / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D066126:Cardiotoxicity; D002985:Clinical Protocols; D006331:Heart Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control*; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods*; D008131:London; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D012039:Regional Blood Flow; D012107:Research Design; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D034941:Upper Extremity / Q000098:blood supply*
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic