Clinical trial NCT05180773: Impact of Bromocriptine on Clinical Outcomes for Peripartum Cardiomyopathy
Official title: Randomized Evaluation of Bromocriptine In Myocardial Recovery THerapy for Peripartum Cardiomyopathy (REBIRTH)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Peripartum Cardiomyopathy, Postpartum
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-01-06
Enrollment: 250
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 200 women meeting all inclusion and exclusion criterial will be randomized in a placebo controlled double blind investigation evaluating the impact of bromocriptine on outcomes for women newly diagnosed with peripartum cardiomyopathy. An additional 50 women in excluded from the trial due to an intent to continue breastfeeding but meeting all other criteria will be enrolled in an observational cohort. All women with receive standard medical care for peripartum cardiomyopathy and will be followed for up to three years.
Primary purpose: TREATMENT

Brief summary: The study will enroll 200 women newly diagnosed with peripartum cardiomyopathy within 5 months postpartum in a randomized placebo controlled trial of bromocriptine therapy to evaluate its impact on myocardial recovery and clinical outcomes. Given that bromocriptine prevents breastfeeding, an additional 50 women with peripartum cardiomyopathy excluded from the trial due to a desire to continue breastfeeding but meeting all other entry criteria will be followed in an observational cohort.

Detailed description: The study will enroll 200 women newly diagnosed with peripartum cardiomyopathy within 5 months postpartum in a randomized trial of bromocriptine therapy to evaluate its impact on myocardial recovery. All women will have an assessment of LVEF demonstrating an LVEF \< or = 0.40 within 4 weeks prior to consent. The women in the breastfeeding cohort will have a qualifying LVEF \< 0.40 within 8 weeks prior to consent. At entry they will then have an assessment of LVEF by echocardiogram which will be repeated at 6- and 12-months post study entry. Subjects in the randomized trial will be randomized to standard medical therapy for heart failure plus placebo or standard therapy plus 8 weeks of bromocriptine (2.5 mg twice daily for 2 weeks then once 2.5 mg daily for 6 weeks). Women receiving bromocriptine not currently on anticoagulation will also receive prophylactic anticoagulation with rivaroxaban 10 mg once daily for 8 weeks.

Primary analysis will compare LVEF at 6 months post entry in the women receiving standard therapy plus bromocriptine to those on standard therapy plus placebo (controlling for initial baseline LVEF). Secondary endpoints will analyze the LVEF in both treatment groups at 12 months post randomization. In addition, subjects will be followed for up to 3 years post randomization and survival free from a major event (cardiac transplantation or durable LVAD implantation) and survival free from heart failure hospitalization will be compared by treatment group.

The benefits of bromocriptine are theoretically related to suppression of prolactin secretion. Breastfeeding increases prolactin levels, and whether continued breastfeeding will impact myocardial recovery in women with peripartum cardiomyopathy remains unknown. As bromocriptine prevents breastfeeding, women who want to continue breastfeeding are excluded from the randomized trial. Up to 50 women meeting all other criteria but excluded from REBIRTH due to an intent to continue to breastfeed will be enrolled in an observational cohort. They will receive standard therapy with no additional intervention and will have the same follow up and assessment of myocardial recovery by echocardiogram at 6- and 12-months post entry as women in the randomized trial.

Blood will be obtained at entry for DNA banking, and analysis of serum, and whole blood RNA . Additional serum and whole blood RNA will be banked at 1-, 3-, and 6-months post randomization. This investigation will evaluate the impact of bromocriptine therapy on the levels of intact 23 kilodalton (kDa) prolactin and the 16 kDa prolactin fragment, as well as microRNA (miR) 146a. The biomarker analysis will also be performed in the observational cohort of women excluded due to continued breast feeding. The impact of these biomarkers on outcomes in both the treatment and control groups as well as the observational cohort excluded due to breastfeeding will be examined.

A core laboratory will analyze all echocardiograms. In addition to quantifying the LVEF at entry, 6 months and 12 months post entry, the core will evaluate global longitudinal strain (LGS) and remodeling (LV volumes) at entry as predictors of outcome and drug response. They will also evaluate the impact of therapy on LGS and LV volumes at 6- and 12-months post randomization.

Eligibility criteria: Inclusion Criteria:

1. Presentation with a new diagnosis of peripartum cardiomyopathy
2. Post-delivery and within the first 5 months post-partum.
3. Clinical assessment of an LVEF \< or =0.40 within 4 weeks of consent for randomized control trial
4. Clinical assessment of an LVEF \< or =0.40 within 8 weeks of consent for breastfeeding cohort
5. Age \> or = 18.

Exclusion Criteria:

1. Previous diagnosis of cardiomyopathy, valvular disease or congenital heart disease (with the exception of women with a history of peripartum cardiomyopathy with complete recovery and a documented LVEF \> 0.55 prior to or in early pregnancy)
2. Refractory hypertension (Systolic \>160 or Diastolic \> 95) either at the time of enrollment or at the time of the qualifying LVEF.
3. Postpartum women currently breastfeeding and planning to continue.
4. Evidence of coronary artery disease (\>50% stenosis of major epicardial vessel or positive non-invasive stress test)
5. Previous cardiac transplant
6. Current durable LVAD support
7. Currently requiring support with extracorporeal membrane oxygenation (ECMO)
8. Current history of alcohol or drug abuse
9. Chemotherapy or chest radiation within 5 years of enrollment
10. Evidence of ongoing bacterial septicemia
11. Medical, social or psychiatric condition which limit the ability to comply with follow-up.

Primary outcomes:
measure: Left ventricular ejection fraction (LVEF) at 6 months post entry as determined by echocardiography
timeFrame: 6 months
Secondary outcomes:
measure: Left ventricular ejection fraction (LVEF) at 12 months post entry as determined by echocardiography
timeFrame: 12 months
measure: Survival free from cardiac transplantation or implantation of a durable left ventricular assist device (LVAD)
timeFrame: 3 years
measure: Survival free from heart failure hospitalization
timeFrame: 3 years
Other outcomes:
measure: Global longitudinal strain (GLS) at 6 months post entry as determined by echocardiography
timeFrame: 6 months
measure: Global longitudinal strain (GLS) at 12 months post entry as determined by echocardiography
timeFrame: 12 months
measure: Left ventricular volumes at 6 months post entry as determined by echocardiography
timeFrame: 6 months
measure: Left ventricular volumes at 12 months post entry as determined by echocardiography
timeFrame: 12 months
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Tucson
country: United States
facility: University of Arizona Sarver Heart Center
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine Health
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic, Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Health Heart Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University/Indiana University Health
state: Indiana
city: Indianapolis
country: United States
facility: Ascension St. Vincent Heart Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinic
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky, Gill Heart & Vascular Institute
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center, Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Columbia
country: United States
facility: Karen L Florio, MD
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Albert Einstein College of Medicine/ Montefiore Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Medicine
state: New York
city: Charlotte
country: United States
facility: Atrium Health Sanger Heart and Vascular Institute
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals, Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma university Health Science Center
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple Heart and Vascular Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Germantown
country: United States
facility: Stern Cardiovascular Foundation, Inc
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: UT Southern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health San Antonio
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: Inova Healthcare Services
state: Virginia
city: Norfolk
country: United States
facility: Old Dominion University
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Pittsburgh
name: Dennis McNamara
role: PRINCIPAL_INVESTIGATOR
References:
citation: Briller JE. Echocardiographic Screening in Hypertensive Pregnancy Disorders: Probing the Window of Opportunity. J Am Coll Cardiol. 2022 Oct 11;80(15):1477-1479. doi: 10.1016/j.jacc.2022.08.717. No abstract available.