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

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ClinicalTrials.gov Identifier: NCT05180773
Recruitment Status : Recruiting
First Posted : January 6, 2022
Last Update Posted : June 14, 2022
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Dennis M. McNamara, MD, MS, University of Pittsburgh

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.

Condition or disease Intervention/treatment Phase
Peripartum Cardiomyopathy, Postpartum Drug: Bromocriptine Drug: Placebo Drug: Guideline Directed Medical Therapy for Heart Failure (GDMT) Drug: Rivaroxaban Drug: Second Placebo Phase 4

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 = 0.35 within 2 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Once consent is obtained the screening sheet will be submitted to the data coordinating center. This will be reviewed to ensure the subject meets criteria for randomization. Subjects will be randomized by the Data Coordinating Center (DCC).
Primary Purpose: Treatment
Official Title: Randomized Evaluation of Bromocriptine In Myocardial Recovery THerapy for Peripartum Cardiomyopathy (REBIRTH)
Estimated Study Start Date : July 1, 2022
Estimated Primary Completion Date : August 30, 2026
Estimated Study Completion Date : January 30, 2027


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:
  • Parlodel
  • Cycloset

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 Name: 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: 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: 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: 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 Name: Placebo

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),




Primary Outcome Measures :
  1. Left ventricular ejection fraction (LVEF) at 6 months post entry as determined by echocardiography [ Time Frame: 6 months ]

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

Other Outcome Measures:
  1. Global longitudinal strain (GLS) at 6 months post entry as determined by echocardiography [ Time Frame: 6 months ]
  2. Global longitudinal strain (GLS) at 12 months post entry as determined by echocardiography [ Time Frame: 12 months ]
  3. Left ventricular volumes at 6 months post entry as determined by echocardiography [ Time Frame: 6 months ]
  4. Left ventricular volumes at 12 months post entry as determined by echocardiography [ Time Frame: 12 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Women recently diagnosed with peripartum cardiomyopathy who are 18 years or older and are within 5 months of postpartum.
Accepts Healthy Volunteers:   No
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 =0.35 within 2 weeks of randomization
  4. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05180773


Contacts
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Contact: Dennis McNamara, MD 412-802-3131 mcnamaradm@upmc.edu

Locations
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United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15237
Contact: Dennis McNamara, MD    412-802-3131    mcnamaradm@upmc.edu   
Contact: Donna Simpson, CRNP, MPH    412-692-3522    simpsondm@upmc.edu   
Principal Investigator: Dennis McNamara, MD         
Sponsors and Collaborators
Dennis M. McNamara, MD, MS
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Dennis McNamara University of Pittsburgh
  Study Documents (Full-Text)

Documents provided by Dennis M. McNamara, MD, MS, University of Pittsburgh:
Statistical Analysis Plan  [PDF] April 11, 2022

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Responsible Party: Dennis M. McNamara, MD, MS, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT05180773    
Other Study ID Numbers: STUDY21090058
UG3HL153847 ( U.S. NIH Grant/Contract )
First Posted: January 6, 2022    Key Record Dates
Last Update Posted: June 14, 2022
Last Verified: June 2022

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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
Additional relevant MeSH terms:
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Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Bromocriptine
Rivaroxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Antiparkinson Agents
Anti-Dyskinesia Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents