Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001094965
Ethics application status
Approved
Date submitted
9/08/2020
Date registered
20/10/2020
Date last updated
5/11/2023
Date data sharing statement initially provided
20/10/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Strain sUrveillance during Chemotherapy for improving Cardiovascular OUtcomes measured by Magnetic Resonance Imaging (SUCCOUR-MRI)
Scientific title
Randomised controlled trial (RCT) of cardioprotection versus usual care for preservation of 12-month MRI ejection fraction in cancer patients with abnormal LV strain but preserved left ventricular (LV) ejection fraction response to chemotherapy
Secondary ID [1] 299256 0
None
Universal Trial Number (UTN)
Trial acronym
SUCCOUR-MRI
Linked study record
ACTRN12614000341628 Is the parent study of randomization to strain imaging for detection of cardiotoxicity

Health condition
Health condition(s) or problem(s) studied:
Cardiotoxicity from cancer chemotherapy 314389 0
Cancer 314391 0
Condition category
Condition code
Cardiovascular 312727 312727 0 0
Other cardiovascular diseases
Cancer 312728 312728 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with a reduced GLS but not EF randomized to cardioprotection;
i) Oral ramipril tablets for the balance of the 12 months since baseline imaging. Dosing starting at 2.5mg/d, uptitrating to 5mg/d in 1 week, 7.5mg/d at 2 weeks and 10 mg/d at 3 weeks.
ii) Oral metoprolol tablets for the balance of the 12 months since baseline imaging. Dosing starting at 50 mg/d, uptitrating to 75mg/day in 1 week and 100mg/d at 3 weeks) . The duration of treatment will be to 12 months from the baseline images.
Intervention code [1] 315544 0
Treatment: Drugs
Comparator / control treatment
Patients with a reduced GLS but not EF randomized to no cardioprotection. Patients in this arm are not told of the change of GLS and no treatment is initiated.
Control group
Active

Outcomes
Primary outcome [1] 321364 0
Change in cardiac magnetic resonance (CMR) ejection fraction from baseline to one year, as determined by a blinded core laboratory
Timepoint [1] 321364 0
12 months post baseline
Secondary outcome [1] 374774 0
Development of cardiotoxicity – ie. a categorical analysis of reduced MRI LVEF concordant with the recent guidelines (reduction of LVEF of more than 5% to less than 50% with symptoms of heart failure, or an asymptomatic reduction of LVEF of more than 10% to less than 50%).
Timepoint [1] 374774 0
12 months post baseline
Secondary outcome [2] 374775 0
Comparison of the proportion with completion of the planned chemotherapy among groups. Data from medical records.
Timepoint [2] 374775 0
12 months post baseline
Secondary outcome [3] 374776 0
Rate of heart failure among groups based on patient history, examination and chart review.
Timepoint [3] 374776 0
36 months post baseline

Eligibility
Key inclusion criteria
i) Patients undergoing chemotherapy at increased risk of cardiotoxicity due to use of anthracycline (already commenced and up to an including 3rd dose) WITH one of the following (not necessarily concurrently)
- trastuzumab (Herceptin) in breast-cancer with the HER2 mutation OR
- tyrosine kinase inhibitors (eg. sunitinib) OR
- cumulative anthracycline doses >450mg/m2 OR
- chest radiotherapy OR
- treatment for previous cancer (solid or haematological) that involved treatment with anthracycline (any dose) or chest radiotherapy OR
- increased risk of HF (age >65y, type 2 diabetes mellitus, hypertension, previous cardiac injury eg.e.g. myocardial infarction)
ii). Live within a geographically accessible area for follow-up
iii). Are able and willing to provide written informed consent to participate in the study (this includes the ability to communicate fluently with the investigator and that the patient is mentally competent)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Unable to provide written informed consent to participate in this study
- Participating in another clinical research trial where randomized treatment would be unacceptable
- Ejection fraction at baseline echo <50%
- Valvular stenosis or regurgitation of >moderate severity
- History of previous heart failure (baseline NYHA >2)
- Systolic BP <110mmHg
- Pulse <60/minute if not on BB
- Inability to acquire interpretable images (identified from baseline echo)
- Contraindications/Intolerance to beta blockers or ACE inhibitors
- Contraindications to MRI
- Oncologic (or other) life expectancy <12 months or any other medical condition (including pregnancy) that results in the belief (deemed by the Chief Investigators) that it is not appropriate for the patient to participate in this trial
- Taking concurrently ACEi AND BB

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A central (web-based) randomization program will be used to allocate patients to cardioprotection (metoprolol and ramipril) vs none only if the patient shows a reduction in GLS but not EF. This allocation concealment will prevent the person performing recruitment from knowing the allocated group at the time of inclusion.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed using a randomisation table created by computer software (i.e. computerised sequence generation) and coded into the RedCap database..
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
An reduction in GLS is expected in 32%, with reduction of EF in 18%, so there is a reduction in GLS only in 14%. To obtain 154 patients to show reduced strain alone, we will recruit 1100 patients.
Cardiotoxicity (reduced 12m EF) will be anticipated in 20% with reduced 3-6 month strain with preserved EF (Grp A),
Based on a similar risk reduction in patients with reduced GLS, 70 completed patients per group would give >90% power to identify a difference with a 5% probability of type 1 error, allowing for the greatest possibility of clustering due to differences in care at different sites (ICC 0.05). At lower ICC values (0.02), the study power would be 95%.


Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/08/2018
Date of last participant enrolment
Anticipated
6/11/2023
Actual
Date of last data collection
Anticipated
30/06/2024
Actual
Sample size
Target
1100
Accrual to date
350
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 14763 0
The Alfred - Melbourne
Recruitment hospital [2] 14764 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 14765 0
Cairns Base Hospital - Cairns
Recruitment hospital [4] 14766 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 27996 0
3004 - Melbourne
Recruitment postcode(s) [2] 27997 0
5000 - Adelaide
Recruitment postcode(s) [3] 27998 0
4870 - Cairns
Recruitment postcode(s) [4] 27999 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 303790 0
Government body
Name [1] 303790 0
NHMRC
Country [1] 303790 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Baker Heart and Daibetes Institute
Address
75 Commercial Road, Melbourne, Vic 3004
Country
Australia
Secondary sponsor category [1] 303913 0
None
Name [1] 303913 0
Address [1] 303913 0
Country [1] 303913 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304311 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 304311 0
Alfred Hospital, 55 Commercial Road, Melbourne, Vic 3004
Ethics committee country [1] 304311 0
Australia
Date submitted for ethics approval [1] 304311 0
07/08/2017
Approval date [1] 304311 0
21/11/2017
Ethics approval number [1] 304311 0
HREC/17/Alfred/32

Summary
Brief summary
Cancer survivors are susceptible to heart failure caused by heart muscle damage from chemotherapy. The purpose of this study is to determine if a test called cardiac strain can be used to predict whether an individual undergoing chemotherapy will develop heart failure.

Who is it for? You may be eligible for this study if you are an adult who is currently undergoing chemotherapy.

Study details: You will have a magnetic resonance scan (MRI) to measure cardiac function at baseline and after 12 months.
You will have a standard heart ultrasound test (echocardiogram) to measure strain and ejection fraction every three months. There are three possible outcomes of this test;
a) The ejection fraction and strain remain normal – you continue with 3 monthly echocardiograms, no treatment is required.
b) The ejection fraction and strain become abnormal – you will be started on medications (ACE inhibitors and beta blockers) to protect the heart
c) If only the strain becomes abnormal and the ejection fraction is normal - you will be randomly selected to continue testing with no treatment, or to take medications (ACE inhibitors and beta blockers) to protect the heart. If you don’t take treatment and the ejection fraction changes, then you will start treatment.
This is the first randomized trial of cardioprotective treatment based on the use of strain measurement. The results of this trial will determine what tests will be done to track the heart’s response to chemotherapy, and to identify how best to respond to abnormal test results.
Trial website
None
Trial related presentations / publications
None
Public notes

Contacts
Principal investigator
Name 96490 0
Prof Thomas Marwick
Address 96490 0
Baker Heart and Diabetes Institute
75 Commercial Road
Melbourne Vic 3004
Country 96490 0
Australia
Phone 96490 0
+61385321550
Fax 96490 0
Email 96490 0
[email protected]
Contact person for public queries
Name 96491 0
Ms Liz Dewar
Address 96491 0
Baker Heart and Diabetes Institute
75 Commercial Road
Melbourne Vic 3004
Country 96491 0
Australia
Phone 96491 0
+61385321550
Fax 96491 0
Email 96491 0
[email protected]
Contact person for scientific queries
Name 96492 0
Ms Liz Dewar
Address 96492 0
Baker Heart and Diabetes Institute
75 Commercial Road
Melbourne Vic 3004
Country 96492 0
Australia
Phone 96492 0
+61385321550
Fax 96492 0
Email 96492 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
No consent obtained for sharing individual data


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
4720Study protocol    378358-(Uploaded-09-08-2020-17-45-48)-Study-related document.docx



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.