Autophagy Activation for the Alleviation of Cardiomyopathy Symptoms After Anthracycline Treatment, ATACAR Trial

May 22, 2023 updated by: Mayo Clinic

AuTophagy Activation for Cardiomyopathy Due to Anthracycline tReatment (ATACAR) Trial

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.

Study Overview

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.

Study Type

Interventional

Phase

  • Phase 2

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 Contact Backup

Study Locations

    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group I (carvedilol, lisinopril)
Patients receive carvedilol orally (PO) and lisinopril orally (PO), up-titrated to maximum tolerated doses as per standard clinical practice for 6 months.
Given PO
Other Names:
  • N2-[(1S)-1-Carboxy-3-phenylpropyl]-L-lysyl-L-proline, Dihydrate
  • Prinivil
  • Zestril
Given PO
Other Names:
  • Coreg
Experimental: Group II (pravastatin, spironolactone)
Patients receive standard clinical practice therapy as in Group I. Patients also receive pravastatin PO and spironolactone PO for 6 months.
Given PO
Other Names:
  • N2-[(1S)-1-Carboxy-3-phenylpropyl]-L-lysyl-L-proline, Dihydrate
  • Prinivil
  • Zestril
Given PO
Other Names:
  • Coreg
Given PO
Other Names:
  • [1S-[1alpha(betaS*,deltaS*),2alpha,6alpha,8beta(R*),8aalpha]]-1,2,6,7,8,8a-Hexahydro-beta,!d,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthaleneheptanoic Acid
Given PO
Other Names:
  • Aldactone
  • 17-Hydroxy-7alpha-mercapto-3-oxo-17alpha-pregn-4-ene-21-carboxylic Acid, gamma Lactone, Acetate
  • SC 9420
  • SPL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Delta change in left ventricular ejection fraction [LVEF])
Time Frame: Baseline up to 6 months
Will be a comparison of the average delta change in LVEF from start to six months of therapy between group 1 and 2 via an independent groups t-test or Wilcoxon as appropriate after testing distributional assumptions.
Baseline up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac function recovery rates between group 1 and group 2
Time Frame: Baseline up to 6 months
Incidence rates will be compared using a simple test for equality of binomial proportions (χ ^ 2 -test or Fisher Exact).
Baseline up to 6 months
Time to recovery of cardiac function between group 1 and group 2
Time Frame: Baseline up to 6 months
Will be a comparison of the average delta change in LVEF from start to six months of therapy between group 1 and 2 via an independent groups t-test or Wilcoxon as appropriate after testing distributional assumptions.
Baseline up to 6 months

Collaborators and Investigators

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

Sponsor

Investigators

  • Principal Investigator: Joerg Herrmann, Mayo Clinic in Rochester

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.

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 (Actual)

September 1, 2020

Primary Completion (Actual)

April 18, 2023

Study Completion (Actual)

April 18, 2023

Study Registration Dates

First Submitted

December 5, 2019

First Submitted That Met QC Criteria

December 5, 2019

First Posted (Actual)

December 9, 2019

Study Record Updates

Last Update Posted (Actual)

May 24, 2023

Last Update Submitted That Met QC Criteria

May 22, 2023

Last Verified

May 1, 2023

More Information

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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