Remote Ischaemic Preconditioning in Childhood Cancer

NCT03166813 | Completed

• 1 other identifier: UW17-143
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Survival rates of children with cancers have improved significantly in the recent few decades. Nonetheless, the side effect of this class of drugs on heart function remains to be an issue of concern. Exploration of new strategies to protect the heart in the long term is therefore of paramount importance in children undergoing treatment of cancers. Previous cardioprotective interventions hav focused on changing the formulation or rate of administration of anthracyclines but with no observable benefits. While dexrazoxane, an iron chelator, has shown to reduce cardiotoxic outcomes, there remains worries of an association between dexrazoxane use and an increased risk of developing secondary malignancies. Recently, the clinical application of remote ischaemic preconditioning (RIPC) as a non-invasive and an easily applicable non-pharmacological myocardial protective intervention has gained increasing interest. Remote ischaemic preconditioning is the phenomenon in which brief episodes of reversible ischaemia and reperfusion applied to one vascular bed render resistance to ischaemia reperfusion injury of tissues and organs distant away. It can be achieved by repeated 5-minute cycles of inflation and deflation of blood pressure cuff placed over the arm or leg to induce limb ischaemia and reperfusion injury. It is noteworthy that anthracycline cardiotoxicity and myocardial reperfusion injury occur through similar pathways. Hence, the investigators hypothesize that RIPC may reduce myocardial injury in children receiving anthracycline chemotherapy for childhood malignancies. The proposed study aims to conduct a parallel-group blinded randomized controlled trial study to investigate whether RIPC may reduce heart damage in childhood cancer patients undergoing anthracycline-based treatment, and to determine the effect of RIPC on the changes in levels of cardiac troponin T, and on the occurrence of clinical cardiovascular events and echocardiographic indices.

Conditions

Cardiotoxicity

Keywords

remote ischaemic preconditioning; childhood cancer; cardio-oncology; anthracycline; myocardial reperfusion injury

Outcome Measures

Primary Outcomes (1)

• High sensitivity cardiac troponin T (hs-cTnT)

  Biomarker of myocardial injury

  hs-cTnT will be measured at baseline, and at 3 months after completion of all anthracycline. The change from baseline hs-cTnT to at 3 months after completion of all anthracycline will be measured.

Secondary Outcomes (2)

• Occurrence of clinical cardiovascular events

  at baseline, within 1 week and at 3 months after completion of all anthracycline treatment.

• Echocardiographic assessment of left ventricular function

  Echocardiographic assessment will be performed at baseline, and within 1 week and at 3 months after completion of all anthracycline treatment.

Study Arms (2)

Intervention RIPC

EXPERIMENTAL

The intervention RIPC protocol will be induced by three cycles of inflation of a blood pressure cuff placed over the upper or lower limb, where deemed to cause minimal discomfort to patient, to 15 mmHg above the systolic blood pressure for five minutes followed by five minutes of cuff deflation to 0 mmHg.

Procedure: Remote Ischaemic Preconditioning

Control

PLACEBO COMPARATOR

The control protocol involves only placement of blood pressure cuff but without inflation for 30 minutes.

Other: Control

Interventions

Remote Ischaemic Preconditioning PROCEDURE

The intervention RIPC protocol will be performed each time by three cycles of inflation of a blood pressure cuff placed over the arm or leg of your child, where deemed to cause minimal discomfort, to 15 mmHg above the systolic blood pressure for 5 minutes followed by 5 minutes of cuff deflation to 0 mmHg.

Also known as: Remote Ischemic Conditioning, Remote Ischaemic Conditioning

Intervention RIPC

Control OTHER

Placement of blood pressure cuff without inflation for 30 minutes.

Also known as: Sham

Control

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• patients aged 4 to 18 years old
• newly diagnosed patients with solid tumours or haematological malignancies referred for anthracycline-based chemotherapy
• no history of being treated with anthracycline-based regimens in the past.

You may not qualify if:

• existence of congenital or acquired heart disease
• presence of syndromal disorders
• abnormal baseline echocardiographic assessment
• peripheral vascular disease that renders RIPC impossible
• a platelet count \<30,000/µL.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Hong Kong Children's Hospital

Hong Kong, Hong Kong

Location

Related Publications (6)

• 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

• Venugopal V, Hausenloy DJ, Ludman A, Di Salvo C, Kolvekar S, Yap J, Lawrence D, Bognolo J, Yellon DM. Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia: a randomised controlled trial. Heart. 2009 Oct;95(19):1567-71. doi: 10.1136/hrt.2008.155770. Epub 2009 Jun 8.

  PMID: 19508973 BACKGROUND

• 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 BACKGROUND

• Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, Holtby HM, Cox PN, Smallhorn JF, Van Arsdell GS, Redington AN. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol. 2006 Jun 6;47(11):2277-82. doi: 10.1016/j.jacc.2006.01.066. Epub 2006 May 15.

  PMID: 16750696 BACKGROUND

• McCrindle BW, Clarizia NA, Khaikin S, Holtby HM, Manlhiot C, Schwartz SM, Caldarone CA, Coles JG, Van Arsdell GS, Scherer SW, Redington AN. Remote ischemic preconditioning in children undergoing cardiac surgery with cardiopulmonary bypass: a single-center double-blinded randomized trial. J Am Heart Assoc. 2014 Jul 28;3(4):e000964. doi: 10.1161/JAHA.114.000964.

  PMID: 25074698 BACKGROUND

• Cheung YF, Li VW, So EK, Cheng FW, Yau JP, Chiu SY, Wong WH, Cheuk DK. Remote Ischemic Conditioning in Pediatric Cancer Patients Receiving Anthracycline Chemotherapy: A Sham-Controlled Single-Blind Randomized Trial. JACC CardioOncol. 2023 Mar 21;5(3):332-342. doi: 10.1016/j.jaccao.2022.11.020. eCollection 2023 Jun.

  PMID: 37397078 DERIVED

MeSH Terms

Conditions

Cardiotoxicity; Neoplasms; 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

• Yiu-fai Cheung, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 25, 2017
• Study Start: July 1, 2017
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: June 8, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)