Impact of Bromocriptine on Clinical Outcomes for Peripartum Cardiomyopathy
Purpose
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
- Peripartum Cardiomyopathy, Postpartum
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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
- Phase
- Phase 4
- Study Type
- Interventional
- 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.
- Primary Purpose
- Treatment
- 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).
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
|
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. |
|
|
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. |
|
Recruiting Locations
Birmingham 4049979, Alabama 4829764 35205
Tucson 5318313, Arizona 5551752 85724
La Jolla 5363943, California 5332921 92037-7411
Los Angeles 5368361, California 5332921 90033
Los Angeles 5368361, California 5332921 90048
Orange 5379513, California 5332921 92868
Stanford 5398563, California 5332921 94305
Aurora 5412347, Colorado 5417618 80045
Hartford 4835797, Connecticut 4831725 06106
New Haven 4839366, Connecticut 4831725 06520
Gainesville 4156404, Florida 4155751 32608
Jacksonville 4160021, Florida 4155751 32216
Tampa 4174757, Florida 4155751 33606
Atlanta 4180439, Georgia 4197000 30322
Chicago 4887398, Illinois 4896861 60611
Chicago 4887398, Illinois 4896861 60612
Indianapolis 4259418, Indiana 4921868 46202
Indianapolis 4259418, Indiana 4921868 46260
Iowa City 4862034, Iowa 4862182 52242
Lexington 4297983, Kentucky 6254925 40536
Shreveport 4341513, Louisiana 4331987 71103
Baltimore 4347778, Maryland 4361885 21201
Baltimore 4347778, Maryland 4361885 21287
Boston 4930956, Massachusetts 6254926 02114
Boston 4930956, Massachusetts 6254926 02115
Ann Arbor 4984247, Michigan 5001836 48109
Detroit 4990729, Michigan 5001836 48202
Minneapolis 5037649, Minnesota 5037779 55407
Minneapolis 5037649, Minnesota 5037779 55455
Rochester 5043473, Minnesota 5037779 55905
Columbia 4381982, Missouri 4398678 65201
Kansas City 4393217, Missouri 4398678 64154
St Louis 4407066, Missouri 4398678 63110
New York 5128581, New York 5128638 10022
New York 5128581, New York 5128638 10029
New York 5128581, New York 5128638 10032
Rochester 5134086, New York 5128638 14642
Stony Brook 5139865, New York 5128638 11794
The Bronx 5110266, New York 5128638 10461
Charlotte 4460243, North Carolina 4482348 28204
Cleveland 5150529, Ohio 5165418 44106
Cleveland 5150529, Ohio 5165418 44195
Oklahoma City 4544349, Oklahoma 4544379 73104
Hershey 5193342, Pennsylvania 6254927 17033
Philadelphia 4560349, Pennsylvania 6254927 19104
Philadelphia 4560349, Pennsylvania 6254927 19140
Pittsburgh 5206379, Pennsylvania 6254927 15237
Providence 5224151, Rhode Island 5224323 02903
Charleston 4574324, South Carolina 4597040 29425
Germantown 4624601, Tennessee 4662168 38138
Nashville 4644585, Tennessee 4662168 37232
Houston 4699066, Texas 4736286 77030
Murray 5778755, Utah 5549030 84107
Burlington 5234372, Vermont 5242283 05401
Charlottesville 4752031, Virginia 6254928 22908
Fairfax 4758023, Virginia 6254928 22031
Norfolk 4776222, Virginia 6254928 23507
Richmond 4781708, Virginia 6254928 23298
Seattle 5809844, Washington 5815135 98195
Madison 5261457, Wisconsin 5279468 53792
Milwaukee 5263045, Wisconsin 5279468 53226
More Details
- NCT ID
- NCT05180773
- Status
- Recruiting
- Sponsor
- Dennis M. McNamara, MD, MS
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.