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.
Brief Title
Impact of Bromocriptine on Clinical Outcomes for Peripartum Cardiomyopathy
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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
412-802-3131
Central Contact Email
mcnamaradm@upmc.edu
Completion Date
Completion Date Type
Estimated
Conditions
Peripartum Cardiomyopathy, Postpartum
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.
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.
Inclusion 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.
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.
Gender
Female
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05180773
Org Class
Other
Org Full Name
University of Pittsburgh
Org Study Id
STUDY21090058
Overall Status
Recruiting
Phases
Phase 4
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Randomized Evaluation of Bromocriptine In Myocardial Recovery THerapy for Peripartum Cardiomyopathy (REBIRTH)
Primary Outcomes
Outcome Measure
Left ventricular ejection fraction (LVEF) at 6 months post entry as determined by echocardiography
Outcome Time Frame
6 months
Secondary Ids
Secondary Id
UG3HL153847
Secondary Outcomes
Outcome Time Frame
12 months
Outcome Measure
Left ventricular ejection fraction (LVEF) at 12 months post entry as determined by echocardiography
Outcome Time Frame
3 years
Outcome Measure
Survival free from cardiac transplantation or implantation of a durable left ventricular assist device (LVAD)
Outcome Time Frame
3 years
Outcome Measure
Survival free from heart failure hospitalization
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sandhya Murthy
Investigator Email
smurthy@montefiore.org
Investigator Phone
718-904-3507