Clinical trial NCT06304896: Colchicine Versus Beta-blockers, Angiotensin-converting Enzyme Inhibitors, and Statins for Prevention of Chemotherapy-Induced Cardiomyopathy
Official title: Colchicine Versus Beta-blockers, Angiotensin-converting Enzyme Inhibitors, and Statins for Prevention of Chemotherapy-Induced Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Chemotherapy Induced Systolic Dysfunction
Lead sponsor: Arab Contractors Medical Centre
Sponsor class: OTHER
First posted: 2024-03-12
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: BASiC-CIC Trial is a multicenter, double-blinded, randomized, placebo-controlled clinical trial to investigate whether repurposing colchicine or a combination of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins will be effective as a prophylactic treatment for the prevention of chemotherapy-induced cardiomyopathy, reduction of major adverse cardiovascular events, and all-cause mortality.

Detailed description: The 2021 European Society of Cardiology (ESC) guidelines recommend that the treatment with angiotensin-converting enzyme inhibitors (ACEi) and a beta-blocker (preferably carvedilol) should be considered in cancer patients developing left ventricle systolic dysfunction, defined as a 10% or more decrease in left ventricular ejection fraction (LVEF) from baseline value or a value lower than 50%, during anthracycline chemotherapy. This statement has a class of recommendation of II with a level of evidence B, which means that the weight of evidence/opinion is in favor of the usefulness of these treatments. The statement recommends starting the dual treatment after echocardiographic evidence of cardiac affection. Therefore, whether pre-treatment with these dual cardio-protective agents will protect the patient's heart from the toxic effects of the chemotherapeutic intervention is unclear.

Additionally, The 2022 ACC/AHA/HFSA American guidelines recommend that in asymptomatic patients with cancer therapy-related cardiomyopathy (ejection fraction\<50%), angiotensin-receptor blocker (ARBs)and beta-blockers are reasonable to prevent progression to heart failure and improve cardiac function. The statement also recommends starting the dual treatment after echocardiographic evidence of cardiac affection. However, these guidelines state that in patients at risk of cancer therapy-related cardiomyopathy, initiation of beta blockers and ACEi/ARB for the primary prevention of drug-induced cardiomyopathy is of uncertain benefit and further clinical research is an unmet need. Accordingly, the effectiveness of preemptive use of ACEi-ARB and/or selected beta-blockers (such as carvedilol and nebivolol) in reducing the risk of cancer therapy-related cardiomyopathy has been investigated in a number of small clinical trials, with conflicting findings. Additionally, statins have pleiotropic therapeutic effects that range from endothelial stabilization to suppression of inflammation. However, its role in decreasing disease morbidity (repeated hospitalization) in established chronic heart failure is also uncertain.

On the other hand, colchicine is an immunomodulator that accumulates in the white blood cells and affects them in a variety of ways including decreasing motility, mobilization, and adhesion. Generally, colchicine appears to inhibit multiple proinflammatory mechanisms, while enabling increased levels of anti-inflammatory mediators. In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received a placebo. Accordingly, colchicine can reduce the risk of cardiovascular events in patients with chronic coronary artery disease, but its efficacy in improving the functional status in patients with established chronic heart failure is also uncertain. While the use of this immunomodulatory agent in established heart failure is uncertain, its effectiveness in the prophylactic reduction of chemotherapy-induced cardiomyopathy in patients with normal pre-treatment ejection fraction has not been investigated.

Accordingly, 150 enrolled cancer patients who are candidates for guideline-directed anthracycline-based chemotherapy with or without the anti-HER2 trastuzumab at the time of presentation, will undergo the following:

* General and Local cardiac examination.
* CBC.
* Chemistry Panel including KFTs, LFTs.
* Serum electrolytes levels.
* Baseline resting surface 12 leads ECG followed by serial recording (monthly for a total of 6 months).
* Baseline Echocardiography followed by serial imaging every 2 months for a total of 6 months.
* Baseline serum BNP test/NT-proBNP followed by serial testing every 2 months for a total of 6 months.

Eligibility criteria: Inclusion Criteria:

* Willing and able to provide written informed consent prior to performing study procedures.
* A cancer patient who is a candidate for a guideline-directed, anthracycline-based chemotherapy with or without the anti-HER2 trastuzumab.
* Baseline LVEF ≥ 50% without evident structural heart disease by pre-treatment echocardiographic examination.

Exclusion Criteria:

* Critically ill Cancer patients who are admitted to ICU.
* Ischemic cardiomyopathy with LVEF ≤ 50%.
* Dilated cardiomyopathy with LVEF ≤ 50%.
* Advanced valvular heart disease (severe valvular affection in the form of stenosis or regurgitation).
* Systolic BP \< 90 mmHg or diastolic BP \< 60 mmHg.
* Liver cell failure.
* End-stage chronic kidney disease on regular dialysis.
* Pregnancy.
* Lactation.
* Chronic muscle diseases such as dermatomyositis, polymyositis, or muscular dystrophy.
* Acute trauma or burns within 2 weeks.
* History of allergy to the implemented drugs.

Primary outcomes:
measure: Chemotherapy-induced cardiomyopathy
timeFrame: 6 months
measure: Chemotherapy-induced cardiomyopathy
timeFrame: 6 months
Secondary outcomes:
measure: Major Adverse Cardiovascular Events
timeFrame: 6 months
measure: All-Cause Mortality
timeFrame: 6 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Arab Contractors Medical Centre
Study officials:
affiliation: Arab Contractors Medical Centre
name: Eslam Abbas, MBChB, MSc
role: PRINCIPAL_INVESTIGATOR
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