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

• ClinicalTrials.gov Identifier: NCT02943590
• Recruitment Status: Completed
• First Posted: October 24, 2016
• Results First Posted: December 18, 2023
• Last Update Posted: December 18, 2023
• Sponsor: Massachusetts General Hospital
• Collaborators: Dana-Farber Cancer Institute; Brigham and Women's Hospital
• Information provided by (Responsible Party): Tomas G. Neilan, MD, Massachusetts General Hospital

Tracking Information

• First Submitted Date: October 21, 2016
• First Posted Date: October 24, 2016
• Results First Submitted Date: October 18, 2023
• Results First Posted Date: December 18, 2023
• Last Update Posted Date: December 18, 2023
• Actual Study Start Date: January 13, 2017
• Actual Primary Completion Date: September 16, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 29, 2023)

The Percentage of Individuals in Each Group With a Significant Decline in the LVEF. [ Time Frame: 12 months ]

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.

Original Primary Outcome Measures (submitted: October 21, 2016)

Left ventricular Ejection Fraction (LVEF) [ Time Frame: 12 months ]

To determine if statins preserve the LVEF at 12 months

Current Secondary Outcome Measures (submitted: November 29, 2023)

• The Percentage of Participants in Each Group With New Onset Heart Failure. [ Time Frame: 2 years ]
  To determine whether statins reduce the percentage of participants in each group with new onset heart failure after anthracyclines.
• Myocardial Extracellular Volume by Cardiac MRI. [ Time Frame: 1 Year ]
  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.
• Global Longitudinal Strain [ Time Frame: 1 Year ]
  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.
• Troponin [ Time Frame: 1 year ]
  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.

Original Secondary Outcome Measures (submitted: October 21, 2016)

• Number of Cardiac Events [ Time Frame: 2 years ]
  To determine whether statins reduce cardiac events (new onset heart failure)
• Myocardial Fibrosis [ Time Frame: 6 months ]
  To determine The Effect Of Statins On Myocardial Fibrosis
• Troponin T and Global Longitudinal Strain [ Time Frame: 3 months ]
  To determine whether changes in troponin T or global longitudinal strain by echocardiography at 3 months predict the reduction in LVEF at 12 months on MRI.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: STOP-CA (Statins TO Prevent the Cardiotoxicity From Anthracyclines)
• Official Title: STOP-CA (Statins TO Prevent the Cardiotoxicity From Anthracyclines)
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Heart Failure

Intervention

• Drug: Placebo
  A pill taken once a day
• Drug: Atorvastatin
  A pill taken once a day
  Other Name: Lipitor

Study Arms

• Placebo Comparator: Placebo
  Placebo will be administered at a pre determined dose The drug is taken by mouth, once a day (evening)
  Intervention: Drug: Placebo
• Experimental: Atorvastatin
  Atorvastatin will be administered at a pre determined dose The drug is taken by mouth, once a day (evening)
  Intervention: Drug: Atorvastatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 21, 2016): 300
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 11, 2023
• Actual Primary Completion Date: September 16, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT02943590
• Other Study ID Numbers: 16-440
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Tomas G. Neilan, MD, Massachusetts General Hospital
• Original Responsible Party: Tomas Neilan, MD, Massachusetts General Hospital, MD
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current

Collaborators

• Dana-Farber Cancer Institute
• Brigham and Women's Hospital

Investigators

• Principal Investigator: Tomas G Neilan, MD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: November 2023