None listed
Conditions
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.
Interventions
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
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.
Sponsors
Baker Heart and Daibetes Institute
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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)
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
Outcome results
None listed