Remote Ischaemic Preconditioning in Childhood Cancer

Cardiotoxicity Clinical Trial

Official title:

Remote Ischaemic Preconditioning in Paediatric Cancer Patients Receiving Anthracycline Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03166813
• Other study ID #: UW17-143
• Status: Completed
• Phase: N/A
• Start date: July 1, 2017
• Est. completion date: June 1, 2022

Study information

• Verified date: June 2022
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Remote ischemic preconditioning (RIPC) protocol will be induced at baseline and before each dose of anthracycline cardiac surgery and once before induction of anesthesia by 3 cycles of 5-min upper or lower limb ischemia and 5-min reperfusion using a blood-pressure cuff inflated to 15 mmHg above the systolic blood pressure for 5 minutes followed by 5 minutes of cuff deflation to 0 mmHg.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: June 1, 2022
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 18 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Cardiotoxicity

Intervention

Procedure:
• Remote Ischaemic Preconditioning
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.

Other:
• Control
Placement of blood pressure cuff without inflation for 30 minutes.

Locations

Country	Name	City	State
Hong Kong	Hong Kong Children's Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (5)

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. — View Citation

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. Epub 2006 May 15. — View Citation

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. — View Citation

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). pii: e000964. doi: 10.1161/JAHA.114.000964. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Occurrence of clinical cardiovascular events	Clinical cardiovascular events include development of clinical congestive heart failure, occurrence of cardiac arrhythmias, the need to institute cardiac medications, and cardiac death	at baseline, within 1 week and at 3 months after completion of all anthracycline treatment.
Secondary	Echocardiographic assessment of left ventricular function	left ventricular systolic and diastolic function	Echocardiographic assessment will be performed at baseline, and within 1 week and at 3 months after completion of all anthracycline treatment.