Effect of Remote Ischaemic Conditioning in Oncology Patients

NCT02471885 | Unknown DMC

• 1 other identifier: 15/0276
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

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 techniques, monitor heart rhythm disturbances (cardiac arrhythmia) and analyse metabolic changes in urine and blood during chemotherapy, at specified time points, and follow up to 5 years after completing chemotherapy treatment).

Conditions

Cardiotoxicity

Keywords

remote ischaemic conditioning; remote ischemic conditioning; cardio-oncology; anthracycline; troponin; chemotherapy; myocardial reperfusion injury

Outcome Measures

Primary Outcomes (1)

• hs-Troponin T (hs-TnT) levels

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

  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

Secondary Outcomes (5)

• Major Adverse Clinical Cardiovascular Event (MACCE)

  1-, 3-, 6-, 12- months follow up

• Echocardiographic global longitudinal strain (GLS)

  at baseline, then at 3- and 12- months follow up

• Incidence of cardiac arrhythmia

  at start of infusion of cycle 5 chemotherapy

• Biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP)

  at 3- months follow up

• Micro ribonucleic acid (RNA) and mitochondrial de-oxyribonucleic acid (DNA) analysis

  at baseline and at 3-months follow up

Study Arms (2)

Remote ischaemic conditioning

EXPERIMENTAL

Remote ischaemic conditioning in the form of a blood pressure cuff on upper arm inflated upto 200 mm Hg (or systolic BP + 20 mm Hg if low platelets e.g. 50-150 x10\^9/L, skip remote ischaemic conditioning (RIC) if platelets \< 50 x 10\^9/L) for 5 minutes, then deflated to 0 mm Hg for 5 minutes, for 4 cycles before beginning of chemotherapy infusion. The entire pre-conditioning phase will last 40 minutes.

Procedure: Remote Ischaemic Conditioning

Control

PLACEBO COMPARATOR

Blood pressure cuff on upper arm inflated to 10 mm Hg for 5 minutes, then deflated to 0 mm Hg for 5 minutes, for 4 cycles before beginning of chemotherapy infusion. The entire control comparator will last 40 minutes

Other: Placebo

Interventions

Remote Ischaemic Conditioning PROCEDURE

each cycle of Remote Ischaemic Conditioning (RIC) consists of inflating a blood pressure cuff on the upper limb (arm) upto 200mm Hg (systolic BP + 20 mm Hg for low platelets, e.g. 50-150 x 10\^9/L; skip RIC if platelets \< 50 x 10\^9/L) for 5 minutes, then deflated to 0 mm Hg for 5 minutes.

Also known as: Remote Ischaemic PreConditioning, Remote Ischemic Conditioning

Remote ischaemic conditioning

Placebo OTHER

Sham control blood pressure cuff placement at 10 mm Hg for 5 minutes, then deflated to 0 mm Hg for 5 minutes.

Also known as: Sham

Control

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult or teenage young adult cancer patients with capacity
• Anthracycline-regimen chemotherapy (de novo or re-challenge)
• Able to tolerate peripheral blood pressure arm cuff inflation

You may not qualify if:

• Recent myocardial infarction in previous 4 weeks
• previous diagnosis of dilated, hypertrophic cardiomyopathy, amyloid or Anderson-Fabry Disease
• peripheral vascular disease
• Chronic Kidney Disease (estimated glomerular filtration rate (GFR) \< 30 ml/min)
• Taking sulphonylureas
• lymph node dissection patients will need BP cuff on contra-lateral arm
• Skip remote ischaemic conditioning (RIC) cycle if very low platelets (e.g. platelets \< 50 x 10\^9/L, can have RIC when platelet counts recover, as per protocol).

Sponsors & Collaborators

• University College, London: lead
• University College London Hospitals: collaborator

Study Sites (1)

University College London Hospitals

London, WC1E 6BT, United Kingdom

RECRUITING

Related Publications (8)

• Candilio L, Malik A, Ariti C, Barnard M, Di Salvo C, Lawrence D, Hayward M, Yap J, Roberts N, Sheikh A, Kolvekar S, Hausenloy DJ, Yellon DM. Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial. Heart. 2015 Feb;101(3):185-92. doi: 10.1136/heartjnl-2014-306178. Epub 2014 Sep 24.

  PMID: 25252696 BACKGROUND

• White SK, Frohlich GM, Sado DM, Maestrini V, Fontana M, Treibel TA, Tehrani S, Flett AS, Meier P, Ariti C, Davies JR, Moon JC, Yellon DM, Hausenloy DJ. Remote ischemic conditioning reduces myocardial infarct size and edema in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2015 Jan;8(1 Pt B):178-188. doi: 10.1016/j.jcin.2014.05.015. Epub 2014 Sep 17.

  PMID: 25240548 BACKGROUND

• Sloth AD, Schmidt MR, Munk K, Kharbanda RK, Redington AN, Schmidt M, Pedersen L, Sorensen HT, Botker HE; CONDI Investigators. Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention. Eur Heart J. 2014 Jan;35(3):168-75. doi: 10.1093/eurheartj/eht369. Epub 2013 Sep 12.

  PMID: 24031025 BACKGROUND

• Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sorensen HT, Redington AN, Nielsen TT. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet. 2010 Feb 27;375(9716):727-34. doi: 10.1016/S0140-6736(09)62001-8.

  PMID: 20189026 BACKGROUND

• Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. 2007 Aug 18;370(9587):575-9. doi: 10.1016/S0140-6736(07)61296-3.

  PMID: 17707752 BACKGROUND

• Davies WR, Brown AJ, Watson W, McCormick LM, West NE, Dutka DP, Hoole SP. Remote ischemic preconditioning improves outcome at 6 years after elective percutaneous coronary intervention: the CRISP stent trial long-term follow-up. Circ Cardiovasc Interv. 2013 Jun;6(3):246-51. doi: 10.1161/CIRCINTERVENTIONS.112.000184. Epub 2013 May 21.

  PMID: 23696599 BACKGROUND

• Mallouppas M, Chung R, Ghosh AK, Macklin A, Yellon DM, Walker JM. Anthracyclines and Biomarkers of Myocardial Injury: The Effect of Remote Ischemic Conditioning. JACC CardioOncol. 2023 May 2;5(3):343-355. doi: 10.1016/j.jaccao.2023.03.008. eCollection 2023 Jun.

  PMID: 37397080 DERIVED

• Chung R, Maulik A, Hamarneh A, Hochhauser D, Hausenloy DJ, Walker JM, Yellon DM. 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. Clin Cardiol. 2016 Feb;39(2):72-82. doi: 10.1002/clc.22507. Epub 2016 Jan 25.

  PMID: 26807534 DERIVED

Related Links

• Hatter Cardiovascular Institute, UCL

MeSH Terms

Conditions

Cardiotoxicity; Myocardial Reperfusion Injury

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Cardiomyopathies; Myocardial Ischemia; Vascular Diseases; Reperfusion Injury; Postoperative Complications

Study Officials

• Derek M Yellon, PhD FACC FAHA

  University College, London

  PRINCIPAL INVESTIGATOR

• Malcolm Walker, MD FRCP

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

• Alison Macklin

  University College London Hospitals

  STUDY DIRECTOR

Central Study Contacts

Robin Chung, MBBS MRCP

CONTACT

02034479880; r.chung@ucl.ac.uk

Michael Mallouppas, MBBS MRCP

CONTACT

02034479880; m.mallouppa@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: June 15, 2015
• Study Start: December 16, 2015
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: April 15, 2020

Record last verified: 2020-04

Locations

GB (1)