Colchicine Versus Beta-blockers, Angiotensin-converting Enzyme Inhibitors, and Statins for Prevention of Chemotherapy-Induced Cardiomyopathy (BASiC-CIC)

March 8, 2024 updated by: Eslam Abbas, MBChB, MSc, Arab Contractors Medical Centre
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Egypt
      • Cairo, Egypt
        • Arab Contractors Medical Centre
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: The Cardioprotective Group (CPG)
50 patients will receive a low-dose Beta-blockers in the form of Carvedilol 6.25 mg PO twice daily, a low-dose ACE inhibitors in the form of Ramipril 2.5 mg PO once daily, and a statin in the form of rosuvastatin 20 mg oral tablets.
Drug: Carvedilol
Carvedilol 6.25 mg oral tablets. Prescribed: Twice daily PO with 200 mL of water.
Other Names:
  • Coreg
  • Carvid
Drug: Ramipril
Ramipril 2.5 mg oral capsules. Prescribed: Once daily PO with 200 mL of water.
Other Names:
  • Altace
  • Tritace
Drug: Rosuvastatin
Rosuvastatin 20 mg oral tablets. Prescribed: Once daily PO with 200 mL of water.
Other Names:
  • Crestor
Active Comparator: The Immunomodulatory Group (IMG)
50 patients will receive Colchicine 0.6 PO once daily.
Drug: Colchicine
Colchicine 0.6 mg oral tablets/capsules. Prescribed: Once daily PO with 200 mL of water.
Other Names:
  • Colcrys
  • Mitigare
Placebo Comparator: The Placebo Control Group (PCG)
50 patients will receive a placebo as a control group.
Drug: Placebo
Placebo oral capsules. Prescribed: Once daily PO with 200 mL of water.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Chemotherapy-induced cardiomyopathy
Time Frame: 6 months
An identification of a drop in the LVEF using echocardiography more than or equal to 10% from the baseline at the time of presentation and/or a decline of the LVEF less than 50%.
6 months
Chemotherapy-induced cardiomyopathy
Time Frame: 6 months
An identification of at least one value of serum NT-proBNP over 125 pg/mL in patients less than 75 years of age, or 450pg/mL in patients more than 75 years of age.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Adverse Cardiovascular Events
Time Frame: 6 months

The non-fatal major cardiovascular adverse events include:

  • Non-fatal myocardial infarction.
  • Non-fatal stroke.
  • Hospitalization due to unstable angina.
  • Hospitalization due to serious arrhythmias.
  • Hospitalization due to heart failure.
6 months
All-Cause Mortality
Time Frame: 6 months
Mortality
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arab Contractors Medical Centre

Investigators

  • Principal Investigator: Eslam Abbas, MBChB, MSc, Arab Contractors Medical Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2024

Primary Completion (Estimated)

May 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

March 5, 2024

First Submitted That Met QC Criteria

March 8, 2024

First Posted (Actual)

March 12, 2024

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 8, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • #18240343

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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