CardiotoxicityNCT03166813
Remote Ischaemic Preconditioning in Childhood Cancer
A study testing Remote Ischaemic Preconditioning in people with Cardiotoxicity, run by The University of Hong Kong at 1 site in Hong Kong.
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. Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Cardiotoxicity
- What is being tested?
- Remote Ischaemic Preconditioning
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Jul 2017to 1 Jun 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Remote Ischaemic Preconditioning in Paediatric Cancer Patients Receiving Anthracycline Therapy
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.
Read the detailed 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.
- Conditions
- Cardiotoxicity
- Being tested
- Remote Ischaemic Preconditioning, Control
- Keywords
- remote ischaemic preconditioning, childhood cancer, cardio-oncology, anthracycline, myocardial reperfusion injury
- Medical subject headings
- Cardiotoxicity, Neoplasms, Myocardial Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote Ischaemic PreconditioningProcedure or surgery
Also called Remote Ischemic Conditioning, Remote Ischaemic Conditioning
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.
ControlOther
Also called Sham
Placement of blood pressure cuff without inflation for 30 minutes.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Remote Ischaemic Preconditioning |
| Control | Placebo comparator | The control protocol involves only placement of blood pressure cuff but without inflation for 30 minutes. Receives: Other: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
High sensitivity cardiac troponin T (hs-cTnT)
Biomarker of myocardial injury
Measured: 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
Clinical cardiovascular events include development of clinical congestive heart failure, occurrence of cardiac arrhythmias, the need to institute cardiac medications, and cardiac death
Measured: 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
Measured: Echocardiographic assessment will be performed at baseline, and within 1 week and at 3 months after completion of all anthracycline treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2017
- Study start1 Jul 2017
- Primary completion1 Jun 2022
- Study completion1 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for CardiotoxicityStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Yiu-fai Cheung, The University of Hong Kong
- Investigators
- Yiu-fai Cheung, MD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03166813
- Sponsor's protocol ID
- UW17-143
- Status last verified
- Jun 2022
- First submitted
- 16 May 2017
- Last updated
- 8 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25252696Venugopal 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.
PubMed 19508973Chung 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.
PubMed 26807534Cheung 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.
PubMed 16750696McCrindle 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.
PubMed 25074698Cheung 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.
PubMed 37397078
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Remote Ischaemic Preconditioning in Paediatric Cancer Patients Receiving Anthracycline Therapy
- ClinicalTrials.gov ID
- NCT03166813
- Acronym / sponsor ID
- UW17-143
- Conditions
- Cardiotoxicity
- Keywords
- remote ischaemic preconditioning, childhood cancer, cardio-oncology, anthracycline, myocardial reperfusion injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 1 Jun 2022 (actual)
- Study completion
- 1 Jun 2022 (actual)
- First posted
- 25 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention RIPC | Experimental | Procedure: Remote Ischaemic PreconditioningThe 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. |
| Control | Placebo comparator | Other: ControlThe control protocol involves only placement of blood pressure cuff but without inflation for 30 minutes. |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remote Ischaemic PreconditioningAlso: Remote Ischemic Conditioning, Remote Ischaemic ConditioningThe 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. | Procedure or surgery | Intervention RIPC |
| ControlAlso: ShamPlacement of blood pressure cuff without inflation for 30 minutes. | Other | Control |
Primary outcome
High sensitivity cardiac troponin T (hs-cTnT)
Time frame: 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.
Biomarker of myocardial injury
2 secondary outcomes
Occurrence of clinical cardiovascular events
Time frame: at baseline, within 1 week and at 3 months after completion of all anthracycline treatment.
Echocardiographic assessment of left ventricular function
Time frame: Echocardiographic assessment will be performed at baseline, and within 1 week and at 3 months after completion of all anthracycline treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2022.
- Background: PubMed 25252696Candilio 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.
- Background: PubMed 19508973Venugopal 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.
- Background: PubMed 26807534Chung 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.
- Background: PubMed 16750696Cheung 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.
- Background: PubMed 25074698McCrindle 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.
- Derived from this study: PubMed 37397078Cheung 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yiu-fai Cheung, MD principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Remote Ischaemic Preconditioning in people with Cardiotoxicity, run by The University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
High sensitivity cardiac troponin T (hs-cTnT) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03166813, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2022.