Clinical trial NCT04190433: Autophagy Activation for the Alleviation of Cardiomyopathy Symptoms After Anthracycline Treatment, ATACAR Trial
Official title: AuTophagy Activation for Cardiomyopathy Due to Anthracycline tReatment (ATACAR) Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Carcinoma
Hematopoietic and Lymphoid Cell Neoplasm
Lymphoma
Sarcoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-12-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This phase II trial compares two drug therapy plans for the correction of heart function changes (reduced ejection function) in patients who have undergone anthracycline-based treatment for lymphoma, sarcoma, or breast cancer. "Reduced ejection fraction" means the left ventricle of the heart is pumping a reduced blood volume with each heartbeat. Treatment is recommended, and the purpose of this research is to compare two different drug therapy plans (standard therapy with carvedilol and lisinopril and standard therapy with carvedilol and lisinopril plus pravastatin and spironolactone) and their effects on improvement of heart function. All of these drugs are heart medications, and carvedilol and lisinopril are commonly used to improve heart function. Adding pravastatin, a cholesterol lowering drug with additional beneficial effects on the cardiovascular system, and spironolactone, a water pill with additional beneficial effects on the cardiovascular system, may lead to even better (and faster) improvements in heart function.

Detailed description: PRIMARY OBJECTIVE:

I. To compare cardiac function changes (delta left ventricular ejection fraction \[LVEF\]) over six months in patients with a new diagnosis of reduced LVEF after anthracycline-based therapy for lymphoma randomized to either standard therapy (carvedilol and lisinopril) or standard therapy plus pravastatin and spironolactone.

SECONDARY OBJECTIVE:

I. To compare cardiac function recovery rates over six months in patients with a new diagnosis of reduced LVEF after anthracycline-based therapy for lymphoma, sarcoma, or breast cancer randomized to either standard therapy (carvedilol and lisinopril) or standard therapy plus pravastatin and spironolactone.

II. To compare the time to recovery of cardiac function in patients with a new diagnosis of reduced LVEF after anthracycline-based therapy for lymphoma, sarcoma, or breast cancer randomized to either standard therapy (carvedilol and lisinopril) or standard therapy plus pravastatin and spironolactone.

OUTLINE: Patients are randomized in to 1 of 2 groups.

GROUP I: Patients receive carvedilol orally (PO) and lisinopril orally (PO), up-titrated to maximum tolerated doses as per standard clinical practice for 6 months.

GROUP II: Patients receive standard clinical practice therapy as in Group I. Patients also receive pravastatin PO and spironolactone PO for 6 months.

After completion of study treatment, patients are followed up at the 6 month visit.

Eligibility criteria: Inclusion Criteria:

* \>= 18 years of age.
* New diagnosis of reduced cardiac function.
* Any prior anthracycline-based cancer therapy for hematological malignancy, breast cancer, or sarcoma.

Exclusion Criteria:

* History of heart failure (HF) of any class and type, or diagnosis of cardiomyopathy prior to anthracycline therapy.
* On active therapy with a fibrate, niacin or eplerenone, or statin.
* History of myopathy/rhabdomyolysis.
* History of statin intolerance.
* Active treatment for hyperlipidemia.
* History of gout.
* Active treatment for liver disease.
* Unexplained persistent elevations of serum transaminases (above upper limit of normal over two weeks).
* Pregnancy.
* Breast-feeding.
* Hyperkalemia (above upper limit of normal).
* Addison disease.
* Estimated glomerular filtration rate (eGFR) \< 30 mL/minute/1.73 m\^2.

Primary outcomes:
measure: Delta change in left ventricular ejection fraction [LVEF])
timeFrame: Baseline up to 6 months
Secondary outcomes:
measure: Cardiac function recovery rates between group 1 and group 2
timeFrame: Baseline up to 6 months
measure: Time to recovery of cardiac function between group 1 and group 2
timeFrame: Baseline up to 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic in Rochester
name: Joerg Herrmann
role: PRINCIPAL_INVESTIGATOR
References: