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.

Robin Chung,Derek M Yellon,Daniel Hochhauser,J Malcolm Walker,Angshuman Maulik,Ashraf Hamarneh,Derek J Hausenloy

doi:10.1002/clc.22507

Abstract

ABSTRACTCancer 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.

Highlights

Cancer affects more than 1 in 3 people in their lifetime and, together with cardiovascular diseases, remains the leading causes of morbidity and mortality in developed nations
Cancer outcomes continue to improve such that long-term 10-year survival for all cancers stands at 50%, and 80% or better for breast, prostate, Hodgkin’s lymphoma, and melanoma.[1]
Cardiovascular mortality in cancer patients is increased due to adverse coronary outcomes,[4] and one-third of long-term cancer survivors will die from cardiovascular causes.[5]

Summary

Introduction

Cancer affects more than 1 in 3 people in their lifetime and, together with cardiovascular diseases, remains the leading causes of morbidity and mortality in developed nations. Received: August 21, 2015 Accepted with revision: November 15, 2015. Rise to a substantial survivor population at risk of longterm cardiovascular consequences, either due to the cancer treatment itself or due to traditional cardiovascular risks. Cardiovascular mortality in cancer patients is increased due to adverse coronary outcomes,[4] and one-third of long-term cancer survivors will die from cardiovascular causes.[5]

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