Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000928819
Ethics application status
Approved
Date submitted
9/06/2021
Date registered
15/07/2021
Date last updated
7/04/2024
Date data sharing statement initially provided
15/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Cessation Of Pharmacotherapy In Recovered Chemotherapy induced cardioToxicity (COP-RCT) – a pilot study
Scientific title
Cessation Of Pharmacotherapy In Recovered Chemotherapy induced cardioToxicity (COP-RCT) – a pilot study
Secondary ID [1] 303891 0
None
Universal Trial Number (UTN)
Trial acronym
COP-RCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recovered chemotherapy induced cardiotoxicity 321470 0
Condition category
Condition code
Cardiovascular 319231 319231 0 0
Other cardiovascular diseases
Cancer 320223 320223 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Supervised withdrawal of cardioprotective therapies will occur in a staged fashion soon post randomisation by the research team, which includes a cardiologist. The prinicipal investigator will be responsible for the overall medication withdrawal.

Firstly, beta-blockers will be titrated down to cessation with weekly dose reductions. Subsequently, angiotensin converting enzyme inhibitors/angiotensin receptor blockers will be titrated down to cessation with weekly dose reductions. We aim for participants to cease all revelant medications within 6 weeks of randomisation.

Should participants experience symptoms suggestive of heart failure, they will be reviewed by the research team and discussed with an independent cardiologist for recommencement of medical therapy.

Adherence to withdrawal will be monitored at protocol stipulated clinical reviews.
Intervention code [1] 320198 0
Treatment: Other
Comparator / control treatment
Continuation of current prescribed cardioprotective therapy will occur for 6 monts post-enrollment. Medication adherence will be monitored at protocol stipulated clinical reviews.
Control group
Active

Outcomes
Primary outcome [1] 327101 0
Change in Left Ventricular Ejection Fraction (LVEF) by cardiac magnetic resonance.
Timepoint [1] 327101 0
6 months post-randomisation
Secondary outcome [1] 393789 0
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score to measure quality of life
Timepoint [1] 393789 0
6 months post-randomisation
Secondary outcome [2] 397617 0
Change in baseline NT-pro-BNP concentration through a blood sample
Timepoint [2] 397617 0
6 months post-randomisation
Secondary outcome [3] 397618 0
Changes in cardiac volumes assessed with cardiac MRI (*depending on funding success)
Timepoint [3] 397618 0
6 months post-randomisation
Secondary outcome [4] 397619 0
Change in EQ-5D survey score to assess quality of life
Timepoint [4] 397619 0
6 months post-randomisation
Secondary outcome [5] 398276 0
Change in baseline Troponin T concentration through a blood sample
Timepoint [5] 398276 0
6 months post-randomisation
Secondary outcome [6] 404931 0
Reduction in 3D Left Ventricular Ejection Fraction (LVEF) of more than 10% and to less than 50% assessed using echocardiogram.
Timepoint [6] 404931 0
6 months post randomisation
Secondary outcome [7] 404932 0
Heart failure requiring hospital admission assessed by review of participant medical records
Timepoint [7] 404932 0
6 months post randomisation
Secondary outcome [8] 404933 0
Worsening heart failure requiring medical treatment as adjudicated by the independent cardiologists.
Timepoint [8] 404933 0
6 months post randomisation
Secondary outcome [9] 406401 0
Change in 3D Left Ventricular Ejection Fraction (LVEF) by echocardiography.
Timepoint [9] 406401 0
6 months post randomisation

Eligibility
Key inclusion criteria
Previously diagnosed asymptomatic chemotherapy related cardiac dysfunction (CTRCD) (defined as: LVEF drop >10% to a value below <55% from baseline or GLS drop greater than or equal to 12% from baseline)

LVEF of >50%.

NYHA Class I

Current CTRCD therapy – Angiotensin Converting Enzyme inhibitor (ACEi) AND/OR Beta Blocker (BB)

Completed HER2 receptor therapy (traztuzumab/pertuzumab)
Minimum age
17 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of ischaemic heart disease
• Hypertension requiring medical therapy
• Moderate or greater severity valvular disease
• Chronic kidney disease
• Atrial, supraventricular, or ventricular arrhythmia requiring BB therapy
• Pregnancy
• < 16 years old

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
14/03/2022
Actual
14/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
70
Accrual to date
17
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 19698 0
Nepean Hospital - Kingswood
Recruitment hospital [2] 21472 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 21473 0
John Hunter Hospital - New Lambton
Recruitment hospital [4] 21474 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 24453 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 34329 0
2747 - Kingswood
Recruitment postcode(s) [2] 36376 0
2298 - Waratah
Recruitment postcode(s) [3] 36377 0
2305 - New Lambton
Recruitment postcode(s) [4] 36378 0
5000 - Adelaide
Recruitment postcode(s) [5] 40035 0
2145 - Westmead
Recruitment outside Australia
Country [1] 24494 0
Singapore
State/province [1] 24494 0
Singapore
Country [2] 24660 0
Japan
State/province [2] 24660 0
Tokyo

Funding & Sponsors
Funding source category [1] 308281 0
University
Name [1] 308281 0
University of Sydney
Country [1] 308281 0
Australia
Funding source category [2] 310555 0
Commercial sector/Industry
Name [2] 310555 0
Takeda
Country [2] 310555 0
Australia
Primary sponsor type
Government body
Name
Nepean Blue Mountains Local Health District
Address
Derby St
Kingswood
NSW
2747
Country
Australia
Secondary sponsor category [1] 309084 0
None
Name [1] 309084 0
Address [1] 309084 0
Country [1] 309084 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308256 0
Nepean Blue Mountains Local Health District Ethic Committee
Ethics committee address [1] 308256 0
Human Research Ethics Office
Nepean Hospital
PO Box 63
Penrith NSW 2751
Ethics committee country [1] 308256 0
Australia
Date submitted for ethics approval [1] 308256 0
02/02/2021
Approval date [1] 308256 0
28/04/2021
Ethics approval number [1] 308256 0
2021/ETH00190

Summary
Brief summary
The purpose of this research is to explore the effect of stopping heart medication in cancer patients whose hearts have recovered from chemotherapy-related cardiac dysfunction (CTRCD).

Who is it for?
You may be eligible for this study if you are aged 18 or older, you have been previously diagnosed with asymptomatic CTRCD and you are currently taking CTRCD medications including Angiotensin Converting Enzyme inhibitors (ACEi) and/or Beta Blockers (BB).

Study details
All participants who choose to enrol in this study will be randomly divided into one of two groups by chance (similar to flipping a coin). One group will continue their heart medications as prescribed. The second group will cease their heart medications (Angiotensin Converting Enzyme inhibitors (ACEi) and/or Beta Blockers (BB)) under medical supervision, this will occur over a staged period. All participants regardless of their group allocation will undergo monthly clincial review. An echocardiogram (heart ultrasound, approximately one hour), Electrocardiogram (ECG), blood tests and cardiac magnetic resonance imaging (CMR) will be taken at the start and end of study involvement.

It is hoped this research will determine whether completely stopping cardiac medications including ACE inhibitors and beta blockers is safe and whether this has any negative impacts on patients with previous chemotherapy related cardiac dysfunction. If this treatment cessation is safe it may be used to improve health outcomes for future cancer patients who are affected by chemotherapy related cardiac dysfunction.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110098 0
Prof Kazuaki Negishi
Address 110098 0
Nepean Clinical School
PO Box 63
Penrith
NSW
2751
Country 110098 0
Australia
Phone 110098 0
+61 2 4734 4278
Fax 110098 0
Email 110098 0
[email protected]
Contact person for public queries
Name 110099 0
Prof Kazuaki Negishi
Address 110099 0
Nepean Clinical School
PO Box 63
Penrith
NSW
2751
Country 110099 0
Australia
Phone 110099 0
+61 2 4734 4278
Fax 110099 0
Email 110099 0
[email protected]
Contact person for scientific queries
Name 110100 0
Prof Kazuaki Negishi
Address 110100 0
Nepean Clinical School
PO Box 63
Penrith
NSW
2751
Country 110100 0
Australia
Phone 110100 0
+61 2 4734 4278
Fax 110100 0
Email 110100 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We do not have ethics consent for sharing of IPD.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.