STOP-CA (Statins TO Prevent the Cardiotoxicity From Anthracyclines)

Study Overview
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Brief Summary
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This research study will test whether atorvastatin, a drug commonly prescribed for reducing cholesterol levels, can protect the heart during chemotherapy with doxorubicin. Atorvastatin is from a family of medications that are commonly called statins

Detailed Description
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This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of a drug and determine whether the investigational drug works in treating a specific disease. Investigational means that the drug is being studied. The chemotherapy drug that the participant have been scheduled to be treated with, Doxorubicin, has been associated with the development of heart failure in some patients. This research study is testing whether Atorvastatin can protect the hearts of patients being treated with Doxorubicin and can reduce cardiac injury and the risk of heart failure. Atorvastatin is not approved by the FDA (the U.S. Food and Drug Administration) for use to reduce the cardiac injury after Doxorubicin. Atorvastatin is approved by the FDA for lowering cholesterol and for reducing the risk of heart attack and stroke. The heart is a muscle that pumps blood and Atorvastatin may protect the heart by preserving cardiac muscle function. The investigators will test whether atorvastatin protects the heart using a combination of imaging tests on the participants heart, blood tests, and stress testing. The imaging tests will involve an echocardiogram (an echo) and cardiac magnetic resonance (CMR), a type of magnetic resonance imaging (MRI) scan.

Official Title
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STOP-CA (Statins TO Prevent the Cardiotoxicity From Anthracyclines)

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Placebo
* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years of age All patients with newly diagnosed NHL and HL Scheduled to receive anthracycline-based therapy Exclusion Criteria: Statin use or Statin use is indicated based on guidelines Pregnancy or breastfeeding Unable to provide informed consent Unexplained persistent elevation of transaminases (>3 times upper limits of normal) Concomitant use of cyclosporine Renal failure: estimated glomerular filtration <45 mL/min/1.73 m2 Contraindication to a CMR (metallic object, severe claustrophobia, pacemaker, vascular clip LVEF of <50% at baseline

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo will be administered at a pre determined dose The drug is taken by mouth, once a day (evening) | Drug: Placebo<br>* A pill taken once a day<br>|
| Experimental: Atorvastatin<br>Atorvastatin will be administered at a pre determined dose The drug is taken by mouth, once a day (evening) | Drug: Atorvastatin<br>* A pill taken once a day<br>* Other names: Lipitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Individuals in Each Group With a Significant Decline in the LVEF. | To determine if the administration of statins is associated with a lower percentage of individuals who experience a significant decline in the LVEF at 12 months. The primary outcome was the percentage of participants with an absolute decline in left ventricular ejection fraction (LVEF) of>10% from prior to chemotherapy to a final value of <55% over 12 months. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants in Each Group With New Onset Heart Failure. | To determine whether statins reduce the percentage of participants in each group with new onset heart failure after anthracyclines. | 2 years | 
| Myocardial Extracellular Volume by Cardiac MRI. | To determine if anthracyclines lead to an increase in myocardial fibrosis, myocardial extracellular volume, as measured by cardiac MRI and whether statins attenuate the increase in myocardial fibrosis. | 1 Year | 
| Global Longitudinal Strain | To determine whether anthracyclines lead to a reduction in global longitudinal strain (GLS), whether the reduction in GLS associates with the decline in LVEF and whether statins attenuate the anthracycline-associated reduction in GLS. | 1 Year | 
| Troponin | To determine if anthracyclines lead to an increase in serum troponin, to determine if the increase in serum troponin related to the decline in cardiac function and whether statins attenuate the increase in serum troponin. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer Treatment Related to Heart Failure