Clinical Trial: Effect of Remote Ischaemic Conditioning in Oncology Patients

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Single Centre Double-blinded Randomized Placebo Controlled Pilot Study Investigating the Effect of Remote Ischaemic preConditioning in ONCology Patients Undergoing Chemotherapy (ERIC-ONC)

Brief Summary:

Cancer survival has improved steadily due to earlier detection and treatment. Despite the established efficacy of anthracycline chemotherapy, its damaging effects on the heart (cardiotoxicity) limits treatment and confers acute and long term adverse cardiovascular consequences. Protective strategies for the heart (cardioprotection) with iron binders (chelation), heart rate (beta blockade) and blood pressure (renin angiotensin inhibition) medications have demonstrated promise in adult cancer patients, but these treatments are typically prescribed only after significant changes in heart chamber size and pumping ability are detected by imaging investigations (myocardial dysfunction).

Furthermore, these conventional therapies are constrained by important side effects that affect bone marrow, blood pressure, and the kidneys.

Remote ischaemic conditioning (RIC) protects the heart by activating cell survival pathways through brief repeated inflations and deflations of a blood pressure cuff to limit blood flow temporarily (noninjurious ischaemia). These innate survival mechanisms prevent part of the cellular injury that occurs during the ischaemia reperfusion cascade during a heart attack (myocardial infarction). Ischaemia reperfusion injury also shares common biochemical pathways with anthracycline cardiotoxicity, and thus RIC may be a novel form of nonpharmacological cardioprotection that can be applied when undergoing anthracycline chemotherapy.

The investigators propose a pilot single centre randomised controlled trial to investigate the effect of RIC on reducing heart muscle damage (myocardial injury) in anthracycline-treated cancer patients. The investigators will assess subclinical myocardial injury using high-sensitivity blood tests (troponin T levels) and advanced imaging

Detailed Summary:

This pilot study aims to demonstrate whether remote ischaemic preconditioning (RIC), delivered as a nonpharmacological treatment via repeated inflations and deflations of a limb blood pressure cuff, can reduce subclinical myocardial injury from anthracycline chemotherapy. Chemotherapy cardiotoxicity is the dose limiting constraint in anthracycline chemotherapy regimens, and conventional drug treatments to prevent and treat it are limited by important interactions with blood pressure, kidney function or bone marrow function. The lifetime cancer risk is between 1 in 2 and 1 in 3 in the general population. Cancer treatment and survival has improved steadily 50% of patients now survive their initial cancer diagnosis, but approximately 25 to 50% of survivors will have abnormal cardiac function over the next twenty years. Historically, anthracycline chemotherapy dosing has been stratified to limit the incidence of clinical heart failure to around 5%. More recent studies have reported at least one third of anthracycline chemotherapy patients demonstrate a significant rise in Troponin levels as a blood biomarker of subclinical myocardial injury as well as documented evidence of biomarker rise even after a single cycle of chemotherapy, and thus the absolute threshold for myocardial injury may be lower and thus more prevalent than these conservative figures.

In standard dosing regimens, chemotherapy may be delayed or suspended in cancer patients based on the simplified measure of ejection fraction (EF) as a measure of cardiac systolic function. Conventional heart failure treatments such as betablockers or ACE inhibitors are usually prescribed only after a significant fall in EF, even though myocardial injury occurs long before this imprecise measurement changes. RIC has been shown to reduce myocardial injury and improve outcomes in elective and emergency percutaneous coronary inter
Sponsor: University College, London

Current Primary Outcome: hs-Troponin T (hs-TnT) levels [ Time Frame: at baseline, at 3-24 hours after end of infusion of each chemotherapy cycle, then at initiation of chemotherapy infusion (cycles 2-6, occurring at intervals of 3-weeks), then at 1-, 3-, 6-, 12- months follow up ]

Biomarker of myocardial injury using high-sensitivity Troponin-T for above time points as serial measurements.


Original Primary Outcome: hs-Troponin T (hs-TnT) area under curve (AUC) [ Time Frame: at baseline, at 6-24 hours after end of infusion of each chemotherapy cycle, then at initiation of chemotherapy infusion (cycles 2-6), then at 1-, 3-, 6-, 12- months follow up ]

Biomarker of myocardial injury using high-sensitivity Troponin-T for above time points as serial measurements for area under curve.


Current Secondary Outcome:

  • Major Adverse Clinical Cardiovascular Event (MACCE) [ Time Frame: 1-, 3-, 6-, 12- months follow up ]
    Major Adverse Cardiovascular Event (myocardial infarction, clinical heart failure requiring admission, life-threatening arrhythmia atrioventricular (AV) block requiring pacemaker, cardiac or cancer death)
  • Echocardiographic global longitudinal strain (GLS) [ Time Frame: at baseline, then at 3- and 12- months follow up ]
    Echocardiographic longitudinal function (GLS %)
  • Incidence of cardiac arrhythmia [ Time Frame: at start of infusion of cycle 5 chemotherapy ]
    two weeks ambulatory electrocardiographic (ECG) monitoring for atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, atrioventricular block
  • Biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: at 3- months follow up ]
    for heart failure / raised left atrial pressure
  • Micro ribonucleic acid (RNA) and mitochondrial de-oxyribonucleic acid (DNA) analysis [ Time Frame: at baseline and at 3-months follow up ]
    Comparison of changes in micro ribonucleic acid (miRNA) and mitochondrial deoxyribonucleic acid (mtDNA), markers of protein expression at baseline (before) and at 3-months' follow up after completing chemotherapy regimen


Original Secondary Outcome:

  • Major Adverse Clinical Cardiovascular Event (MACCE) [ Time Frame: 1-, 3-, 6-, 12- months follow up ]
    Major Adverse Cardiovascular Event (myocardial infarction, clinical heart failure requiring admission, life-threatening arrhythmia atrioventricular (AV) block requiring pacemaker, cardiac or cancer death)
  • Echocardiographic global longitudinal strain (GLS) [ Time Frame: at baseline, then at 3- and 12- months follow up ]
    Echocardiographic longitudinal function (GLS %)
  • Incidence of cardiac arrhythmia [ Time Frame: at start of infusion of cycle 5 chemotherapy ]
    two weeks ambulatory electrocardiographic (ECG) monitoring for atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, atrioventricular block
  • Biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: at 3- months follow up ]
    for heart failure / raised left atrial pressure
  • Micro ribonucleic acid (RNA) and mitochondrial de-oxyribonucleic acid (DNA) analysis [ Time Frame: at baseline and at 3-months follow up ]
    Comparison of changes in micro ribonucleic acid (miRNA) and mitochondrial deoxyribonucleic acid (mtDNA) marker expression at baseline (before) and at 3-months' follow up after completing chemotherapy regimen


Information By: University College, London

Dates:
Date Received: May 5, 2015
Date Started: December 2015
Date Completion: December 2017
Last Updated: October 13, 2016
Last Verified: November 2015