Impact of Bromocriptine on Clinical Outcomes for Peripartum Cardiomyopathy (REBIRTH)

February 8, 2024 updated by: Dennis M. McNamara, MD, MS

Randomized Evaluation of Bromocriptine In Myocardial Recovery THerapy for Peripartum Cardiomyopathy (REBIRTH)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

250

Phase

  • Phase 4

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 Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35205
        • Recruiting
        • University of Alabama Birmingham
        • Principal Investigator:
          • Gretchen Wells, MD
        • Contact:
        • Contact:
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Recruiting
        • University of Arizona Sarver Heart Center
        • Contact:
        • Principal Investigator:
          • Elizabeth Juneman, MD
    • California
      • La Jolla, California, United States, 92037-7411
        • Recruiting
        • University of California San Diego
        • Contact:
        • Principal Investigator:
          • Hilary Shapiro, MD
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Contact:
        • Principal Investigator:
          • Janet Wei, MD
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Keck School of Medicine of USC
        • Contact:
        • Principal Investigator:
          • Uri Elkayam, MD
      • Orange, California, United States, 92868
        • Recruiting
        • University of California Irvine Health
        • Contact:
        • Principal Investigator:
          • Afshan Hameed, MD
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford University
        • Contact:
        • Principal Investigator:
          • Abha Khandelwal, M.D.
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Anschutz Medical Campus
        • Contact:
        • Principal Investigator:
          • Josephine Chou, MD
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University
        • Contact:
        • Principal Investigator:
          • Sarah Goldstein, MD
    • Florida
      • Gainesville, Florida, United States, 32608
      • Jacksonville, Florida, United States, 32216
        • Recruiting
        • Mayo Clinic, Florida
        • Principal Investigator:
          • Demilade Adedinsewo, MD, MPH
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lakshmi Sridharan, MD
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Contact:
        • Principal Investigator:
          • Priya Freaney, MD
        • Contact:
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois Health Heart Center
        • Contact:
        • Principal Investigator:
          • Joan Briller, MD
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University/Indiana University Health
        • Contact:
        • Principal Investigator:
          • Maya Guglin, MD
      • Indianapolis, Indiana, United States, 46260
        • Recruiting
        • Ascension St. Vincent Heart Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Mary Walsh, M.D.
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa Hospitals and Clinic
        • Principal Investigator:
          • Linda Cadaret, MD
        • Contact:
        • Contact:
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky, Gill Heart & Vascular Institute
        • Contact:
        • Principal Investigator:
          • Navin Rajagopalan, M.D.
        • Contact:
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • Recruiting
        • Louisiana State University
        • Contact:
        • Principal Investigator:
          • Kalgi Modi, MD
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University
        • Contact:
        • Principal Investigator:
          • Nisha Gilotra, M.D.
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland Medical Center, Baltimore
        • Contact:
        • Principal Investigator:
          • Manjula Ananthram, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Principal Investigator:
          • Michael Givertz, M.D.
        • Contact:
        • Contact:
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Principal Investigator:
          • Nandita S. Scott, MD FACC
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Contact:
        • Principal Investigator:
          • Melinda Davis, MD
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health System
        • Principal Investigator:
          • Ryhm Radjef, M.D.
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic, Rochester
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kathleen Young, MD
    • Missouri
      • Columbia, Missouri, United States, 65201
        • Recruiting
        • Karen L Florio, MD
        • Contact:
        • Principal Investigator:
          • Karen L Florio, MD
      • Kansas City, Missouri, United States, 64154
        • Recruiting
        • Saint Luke's Hospital of Kansas City
        • Contact:
        • Principal Investigator:
          • Anna Grodzinsky, MD,MSc
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Principal Investigator:
          • Gregory Ewald, M.D.
        • Contact:
    • New York
      • Bronx, New York, United States, 10461
        • Recruiting
        • Albert Einstein College of Medicine/ Montefiore Medical Center
        • Contact:
        • Principal Investigator:
          • Sandhya Murthy, M.D.
        • Principal Investigator:
          • Diana S. Wolfe, MD, MPH
        • Contact:
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
        • Contact:
        • Principal Investigator:
          • Jennifer Haythe, MD
      • New York, New York, United States, 10029
        • Recruiting
        • Mount Sinai Hospital
        • Contact:
        • Principal Investigator:
          • Anuradha Lala-Trindade, MD
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester
        • Contact:
        • Principal Investigator:
          • Jeffrey Alexis, MD
      • Stony Brook, New York, United States, 11794
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Principal Investigator:
          • Eileen Hsich, MD
        • Contact:
          • Barbara Gus
          • Phone Number: 216-445-6552
          • Email: gusb@ccf.org
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • University Hospitals, Cleveland Medical Center
        • Contact:
        • Principal Investigator:
          • Chantal ElAmm, MD
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • Oklahoma University Health Science Center
        • Contact:
        • Principal Investigator:
          • Tarun Dasari, M.D.
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Recruiting
        • Lehigh Valley Health Network
        • Contact:
        • Principal Investigator:
          • Amy Ahnert, M.D.
      • Hershey, Pennsylvania, United States, 17033
      • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia, Pennsylvania, United States, 19140
        • Recruiting
        • Temple Heart and Vascular Institute
        • Contact:
        • Principal Investigator:
          • Deborah Crabbe, MD
      • Pittsburgh, Pennsylvania, United States, 15237
        • Recruiting
        • University of Pittsburgh Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Dennis McNamara, MD
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Rhode Island Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Athena Poppas, MD
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Contact:
        • Contact:
        • Principal Investigator:
          • Stephanie Gaydos, MD
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt
        • Contact:
        • Principal Investigator:
          • Julie Damp, MD
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern Medical Center
        • Principal Investigator:
          • Sonia Garg, M.D.
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • University of Texas Health San Antonio
        • Principal Investigator:
          • Ildiko Agoston, MD
        • Contact:
        • Contact:
    • Utah
      • Murray, Utah, United States, 84107
        • Recruiting
        • Intermountain Medical Center
        • Contact:
        • Principal Investigator:
          • Rami Alharethi, M.D.
    • Vermont
      • Burlington, Vermont, United States, 05401
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia
        • Contact:
        • Principal Investigator:
          • Patricia Rodriguez-Lozano M.D, MD
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University
        • Contact:
        • Principal Investigator:
          • Krishnasree Rao, MD
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington Medical Center
        • Contact:
        • Principal Investigator:
          • April Stempien-Otero, MD, FACC
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Contact:
        • Principal Investigator:
          • Sarah Thordsen, MD

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

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Bromocriptine Treatment Arm
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.
Drug: Bromocriptine
Bromocriptine 2.5 mg one tablet by mouth twice daily for 2 weeks then once daily for 6 weeks. Subjects not on anticoagulation at the time of entry will also receive rivaroxaban 10 mg tablets once daily for 8 weeks while on bromocriptine.
Other Names:
  • Cycloset
  • Parlodel
Drug: Guideline Directed Medical Therapy for Heart Failure (GDMT)
GDMT will potentially include angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor antagonists (ARB), angiotensin receptor blocker-neprilysin inhibitors (ARNI), beta adrenergic receptor antagonists (beta blockers) , Mineralocorticoid receptor antagonists (MRA), sodium-glucose cotransporter-2 inhibitors (SGLT2i),
Drug: Rivaroxaban
Subjects not on anticoagulation clinically who are randomized to bromocriptine will receive rivaroxaban 10 mg tablets once tablet by mouth daily for 8 weeks while on bromocriptine.
Other Names:
  • Xarelto
Placebo Comparator: Placebo Arm
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.
Drug: Guideline Directed Medical Therapy for Heart Failure (GDMT)
GDMT will potentially include angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor antagonists (ARB), angiotensin receptor blocker-neprilysin inhibitors (ARNI), beta adrenergic receptor antagonists (beta blockers) , Mineralocorticoid receptor antagonists (MRA), sodium-glucose cotransporter-2 inhibitors (SGLT2i),
Drug: Placebo
Placebo one tablet by mouth twice daily for 2 weeks then once daily for 6 weeks. Subjects who are not on anticoagulation will not receive rivaroxaban but will receive a second placebo once daily for 8 weeks while on study drug.
Drug: Second Placebo
Subjects not on anticoagulation clinically who are randomized to placebo (rather than bromocriptine) will receive a second placebo one tablet by mouth daily for 8 weeks.
Other Names:
  • Placebo
Other: Breastfeeding Observational Cohort
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.
Drug: Guideline Directed Medical Therapy for Heart Failure (GDMT)
GDMT will potentially include angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor antagonists (ARB), angiotensin receptor blocker-neprilysin inhibitors (ARNI), beta adrenergic receptor antagonists (beta blockers) , Mineralocorticoid receptor antagonists (MRA), sodium-glucose cotransporter-2 inhibitors (SGLT2i),

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Left ventricular ejection fraction (LVEF) at 6 months post entry as determined by echocardiography
Time Frame: 6 months
6 months

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Time Frame
Global longitudinal strain (GLS) at 6 months post entry as determined by echocardiography
Time Frame: 6 months
6 months
Global longitudinal strain (GLS) at 12 months post entry as determined by echocardiography
Time Frame: 12 months
12 months
Left ventricular volumes at 6 months post entry as determined by echocardiography
Time Frame: 6 months
6 months
Left ventricular volumes at 12 months post entry as determined by echocardiography
Time Frame: 12 months
12 months

Collaborators and Investigators

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

Sponsor

Dennis M. McNamara, MD, MS

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Dennis McNamara, University of Pittsburgh

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.

General Publications

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)

July 27, 2022

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

December 9, 2021

First Submitted That Met QC Criteria

January 4, 2022

First Posted (Actual)

January 6, 2022

Study Record Updates

Last Update Posted (Actual)

February 12, 2024

Last Update Submitted That Met QC Criteria

February 8, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY21090058
  • UG3HL153847 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

Clinical Trials on Peripartum Cardiomyopathy, Postpartum

Clinical Trials on Bromocriptine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kyrgyzstan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe