Remote Ischaemic Preconditioning in Childhood Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Remote Ischaemic Preconditioning in Paediatric Cancer Patients Receiving Anthracycline Therapy

Conditions
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Cardiotoxicity

Intervention / Treatment
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* Procedure: Remote Ischaemic Preconditioning
* Other: Control


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention RIPC<br>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<br>* 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.<br>* Other names: Remote Ischaemic Conditioning;|
| Placebo Comparator: Control<br>The control protocol involves only placement of blood pressure cuff but without inflation for 30 minutes. | Other: Control<br>* Placement of blood pressure cuff without inflation for 30 minutes.<br>* Other names: Sham;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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remote ischaemic preconditioning, childhood cancer, cardio-oncology, anthracycline, myocardial reperfusion injury