Impact of Bromocriptine on Clinical Outcomes for Peripartum Cardiomyopathy

Phase 4

Recruiting

• Conditions: Peripartum Cardiomyopathy, Postpartum
• Interventions: Drug: Guideline Directed Medical Therapy for Heart Failure (GDMT); Drug: Placebo; Drug: Bromocriptine; Drug: Second Placebo; Drug: Rivaroxaban

• Registration Number: NCT05180773
• Lead Sponsor: Dennis M. McNamara, MD, MS

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.

Study Timeline

• Study First Submitted: 2021-12-09
• Study First Submitted QC: 2022-01-04
• Study First Posted: 2022-01-06
• Study Start: 2022-07-27
• Status Verified: 2025-02
• Last Update Submitted: 2025-09-16
• Last Update Posted: 2025-09-22
• Primary Completion: 2026-06-30
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 250

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Arm	Second Placebo	100 Women in the Placebo Arm will receive guideline directed medical therapy for heart failure plus 8 weeks of a placebo administered orally twice daily for 2 weeks then once daily for 6 weeks. Women not on clinical anticoagulation will not receive rivaroxaban but will instead receive a second placebo for 8 weeks.
Breastfeeding Observational Cohort	Guideline Directed Medical Therapy for Heart Failure (GDMT)	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 guideline directed medical therapy with no additional interventions 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.
Bromocriptine Treatment Arm	Guideline Directed Medical Therapy for Heart Failure (GDMT)	100 Women in the Treatment Arm will receive guideline directed medical therapy for heart failure plus 8 weeks of bromocriptine administered orally as 2.5 mg twice daily for 2 weeks then 2.5mg once daily for 6 weeks. Women not on clinical anticoagulation will also receive prophylactic anticoagulation with rivaroxaban 10 mg once daily for 8 weeks while on bromocriptine.
Placebo Arm	Guideline Directed Medical Therapy for Heart Failure (GDMT)	100 Women in the Placebo Arm will receive guideline directed medical therapy for heart failure plus 8 weeks of a placebo administered orally twice daily for 2 weeks then once daily for 6 weeks. Women not on clinical anticoagulation will not receive rivaroxaban but will instead receive a second placebo for 8 weeks.
Placebo Arm	Placebo	100 Women in the Placebo Arm will receive guideline directed medical therapy for heart failure plus 8 weeks of a placebo administered orally twice daily for 2 weeks then once daily for 6 weeks. Women not on clinical anticoagulation will not receive rivaroxaban but will instead receive a second placebo for 8 weeks.
Bromocriptine Treatment Arm	Bromocriptine	100 Women in the Treatment Arm will receive guideline directed medical therapy for heart failure plus 8 weeks of bromocriptine administered orally as 2.5 mg twice daily for 2 weeks then 2.5mg once daily for 6 weeks. Women not on clinical anticoagulation will also receive prophylactic anticoagulation with rivaroxaban 10 mg once daily for 8 weeks while on bromocriptine.
Bromocriptine Treatment Arm	Rivaroxaban	100 Women in the Treatment Arm will receive guideline directed medical therapy for heart failure plus 8 weeks of bromocriptine administered orally as 2.5 mg twice daily for 2 weeks then 2.5mg once daily for 6 weeks. Women not on clinical anticoagulation will also receive prophylactic anticoagulation with rivaroxaban 10 mg once daily for 8 weeks while on bromocriptine.

Primary Outcome Measures

Name	Time	Method
Left ventricular ejection fraction (LVEF) at 6 months post entry as determined by echocardiography	6 months

Secondary Outcome Measures

Name	Time	Method
Survival free from cardiac transplantation or implantation of a durable left ventricular assist device (LVAD)	3 years
Survival free from heart failure hospitalization	3 years
Left ventricular ejection fraction (LVEF) at 12 months post entry as determined by echocardiography	12 months

Trial Locations

Locations (64)

University of Alabama Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Arizona Sarver Heart Center; 🇺🇸 Tucson, Arizona, United States

University of California San Diego; 🇺🇸 La Jolla, California, United States

Keck School of Medicine of USC; 🇺🇸 Los Angeles, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

University of California Irvine Health; 🇺🇸 Orange, California, United States

Stanford University; 🇺🇸 Stanford, California, United States

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

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