Bromocriptine for Peripartum Cardiomyopathy

(REBIRTH Trial)

Recruiting at 64 trial locations

Overseen By Eileen Hsich, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Dennis McNamara

Disqualifiers: Cardiomyopathy, Hypertension, Breastfeeding, Coronary artery disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well bromocriptine, a medication for certain medical conditions, aids women in recovering from peripartum cardiomyopathy, a heart condition that can develop shortly after childbirth. Researchers will compare bromocriptine's effects to a placebo to assess its impact on heart health and overall outcomes. Women diagnosed with peripartum cardiomyopathy within five months of giving birth, who do not plan to continue breastfeeding, might be suitable candidates for the trial. Additionally, those who wish to continue breastfeeding but have the condition can join an observational group to monitor heart recovery without taking bromocriptine. As a Phase 4 trial, bromocriptine is already FDA-approved and proven effective, and this research aims to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for bromocriptine?

Research has shown that bromocriptine is generally safe for patients with peripartum cardiomyopathy, a type of heart weakness occurring around childbirth. Studies have found that patients taking bromocriptine often experience improved heart function compared to those receiving standard treatments. Reports indicate that bromocriptine can aid heart recovery after pregnancy, particularly for those with more severe heart problems.

Some studies have used doses similar to those in this trial, and patients experienced good heart recovery. Bromocriptine is also used for other health issues, providing additional safety information. However, like any medication, it may have side effects, so discussing these with a doctor is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for peripartum cardiomyopathy, which typically involve heart failure medications like beta-blockers and ACE inhibitors, bromocriptine targets the condition differently by inhibiting prolactin secretion. Researchers are excited about bromocriptine because it tackles a possible underlying cause of the condition, offering a novel approach beyond just managing symptoms. Additionally, bromocriptine's use in this context is coupled with prophylactic anticoagulation, potentially enhancing safety and effectiveness in women not already on blood thinners. This combination could provide a more comprehensive strategy for improving heart function in affected women.

What evidence suggests that bromocriptine could be an effective treatment for peripartum cardiomyopathy?

Research has shown that bromocriptine, which participants in this trial may receive, can help women with peripartum cardiomyopathy (PPCM), a heart condition that can occur after childbirth. Studies found that women who took bromocriptine experienced better heart function and outcomes after six months compared to those who did not. Specifically, bromocriptine led to greater improvement in the heart's ability to pump blood, known as left ventricular ejection fraction (LVEF), and overall better heart health. Importantly, these benefits did not come with a higher risk of blood clots. Overall, bromocriptine shows promise in improving the heart health of women with PPCM. ^{1 6 7 8 9}

Who Is on the Research Team?

Dennis McNamara

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for women over 18 who've been diagnosed with peripartum cardiomyopathy within 5 months after giving birth. They must have a left ventricular ejection fraction (LVEF) of 0.35 or less and cannot be breastfeeding if they wish to participate.

Inclusion Criteria

Post-delivery and within the first 5 months post-partum

Presentation with a new diagnosis of peripartum cardiomyopathy

Clinical assessment of an LVEF ≤0.40 within 4 weeks of consent for randomized control trial

Exclusion Criteria

I have not had chemotherapy or chest radiation in the last 5 years.

I have had heart disease, except for fully recovered peripartum cardiomyopathy.

Currently requiring support with extracorporeal membrane oxygenation (ECMO)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4-8 weeks

Treatment

Participants receive either bromocriptine or placebo for 8 weeks, with bromocriptine administered as 2.5 mg twice daily for 2 weeks then 2.5 mg once daily for 6 weeks. Women not on clinical anticoagulation receive prophylactic anticoagulation with rivaroxaban.

8 weeks

Follow-up

Participants are monitored for myocardial recovery and clinical outcomes, with echocardiograms at 6 and 12 months post entry. Biomarker analysis is performed at 1, 3, and 6 months.

12 months

Long-term Follow-up

Participants are followed for up to 3 years post randomization to assess survival free from major events and heart failure hospitalization.

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bromocriptine
• Guideline Directed Medical Therapy for Heart Failure (GDMT)
• Placebo
• Rivaroxaban
• Second Placebo

Trial Overview

The study tests the effect of Bromocriptine, compared to a placebo, on heart muscle recovery in women with recent onset peripartum cardiomyopathy. It also includes standard heart failure therapy and Rivaroxaban, an anticoagulant, versus another placebo.

How Is the Trial Designed?

Group I: Breastfeeding Observational Cohort Experimental Treatment 1 Intervention

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.

Group II: Bromocriptine Treatment Arm Active Control 3 Interventions

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.

Group III: Placebo Arm Placebo Group 3 Interventions

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 is already approved in European Union, United States for the following indications:

Approved in European Union as Parlodel for:

• Hyperprolactinemia
• Parkinson's disease
• Acromegaly
• Type 2 diabetes

Approved in United States as Parlodel for:

• Hyperprolactinemia
• Parkinson's disease
• Acromegaly
• Type 2 diabetes

Approved in United States as Cycloset for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Dennis McNamara

Lead Sponsor

Trials

1

Recruited

250+

Dennis M. McNamara, MD, MS

Lead Sponsor

Trials

1

Recruited

250+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Cabergoline, a prolactin secretion inhibitor, was successfully used to treat four cases of peripartum cardiomyopathy, including one severe case that required mechanical circulatory support.

This study suggests that Cabergoline may be an effective alternative treatment for peripartum cardiomyopathy, a serious condition that typically requires urgent medical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Succès de traitement par Cabergoline d'une série de cas de cardiomyopathie du péripartum, incluant un cas critique nécessitant une assistance circulatoire mécanique]. Hamdan, R., Abdallah, Y., Gafar, S., et al.[2023]

Bromocriptine shows promise as a treatment for peripartum cardiomyopathy (PPCM), based on a review of 17 case reports, suggesting it may help improve outcomes for some patients.

However, there is not enough evidence to recommend bromocriptine for all PPCM patients, indicating that its use should be tailored to individual cases alongside standard heart failure therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bromocriptine Use in Peripartum Cardiomyopathy: Review of Cases. Simon, R., Yang, S., Hameed, AB.[2020]

A 35-year-old woman with severe peripartum cardiomyopathy (PPCM) showed significant improvement in heart function after being treated with bromocriptine, a drug that blocks prolactin, alongside standard heart failure therapy.

Within a week of starting bromocriptine, her symptoms improved to NYHA functional class II, and two months later, her heart function normalized with an LVEF of 60%, suggesting bromocriptine may be a promising treatment for severe PPCM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recovery from peripartum cardiomyopathy after treatment with bromocriptine. Habedank, D., Kühnle, Y., Elgeti, T., et al.[2016]

Bromocriptine, used for postpartum lactation suppression, has been linked to serious complications, including a case of maternal death potentially caused by a heart attack in a patient with hidden coronary artery disease.

The findings highlight the need for caution when prescribing bromocriptine, particularly for patients with known risk factors for heart disease or vascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal myocardial infarction associated with bromocriptine for postpartum lactation suppression. Dutt, S., Wong, F., Spurway, JH.[2019]

Concurrent administration of oral prednisolone significantly reduces acute side effects, such as light-headedness and nausea, associated with the initiation of depot bromocriptine therapy in patients with hyperprolactinaemia.

In a double-blind placebo-controlled trial involving 21 patients, those who received prednisolone experienced fewer adverse effects compared to the placebo group, suggesting that this approach could enhance the safety of dopamine agonist treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral prednisolone supplement abolishes the acute adverse effects following initiation of depot bromocriptine therapy. Jenkins, PJ., Jain, A., Jones, SL., et al.[2019]

Bromocriptine mesylate, used to suppress lactation after childbirth, can lead to serious side effects, including vasospasm of blood vessels, which may result in cardiac or cerebral complications.

Case reports suggest that bromocriptine may exacerbate hyperthyroidism symptoms and potentially trigger chronic hypertension in predisposed women, highlighting the need for caution in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bromocriptine related atypical vascular accidents postpartum identified through medicolegal reviews. Iffy, L., McArdle, JJ., Ganesh, V., et al.[2017]

Bromocriptine mesylate, previously used for postpartum milk suppression, was withdrawn from the market due to serious side effects, including postpartum intracranial hemorrhages, with over a dozen cases reported since its disqualification.

In a new case study, one patient developed hypertension and a headache after taking bromocriptine, leading to intracranial hemorrhage, suggesting that the drug may induce high blood pressure, which could be a contributing factor to this serious complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of hypertension in bromocriptine-related puerperal intracranial hemorrhage. Kirsch, C., Iffy, L., Zito, GE., et al.[2019]

Bromocriptine has shown efficacy in treating peripartum cardiomyopathy (PPCM), a serious condition that can occur during late pregnancy or shortly after childbirth.

The treatment works by blocking prolactin, which is linked to oxidative stress and impaired heart function, suggesting a potential mechanism for its effectiveness in managing PPCM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of bromocriptine treatment in a patient with peripartum cardiomyopathy. Ichida, M., Katsurada, K., Komori, T., et al.[2020]

Bromocriptine mesylate, once used for preventing breast engorgement after childbirth, was withdrawn from the U.S. market in 1994 due to severe side effects, including vasospastic reactions that could lead to serious conditions like stroke and myocardial infarction.

Recent reports indicate that bromocriptine may also cause circulatory collapse due to cardiac dysrhythmia, particularly in patients who are already predisposed to arrhythmias, highlighting the need for caution in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe cardiac dysrhythmia in patients using bromocriptine postpartum. Iffy, L., O'Donnell, J., Correia, J., et al.[2022]

In a study of 40 patients with peripartum cardiomyopathy (PPCM), bromocriptine treatment was associated with significant improvements in both right ventricular (RV) and left ventricular (LV) function, particularly in patients with initial RV dysfunction.

Patients receiving long-term bromocriptine treatment showed a higher rate of full RV recovery (79%) compared to those on short-term treatment (40%), indicating that bromocriptine may enhance recovery in PPCM patients with biventricular impairment, although the differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bromocriptine treatment in patients with peripartum cardiomyopathy and right ventricular dysfunction. Haghikia, A., Schwab, J., Vogel-Claussen, J., et al.[2020]

Combining bromocriptine with standard heart failure treatment significantly improved left ventricular ejection fraction (LVEF) by 11.37% after six months in women with peripartum cardiomyopathy (PPCM), based on a systematic review of six studies involving 263 patients.

The addition of bromocriptine not only enhanced heart function but also reduced mortality rates associated with PPCM, with no thromboembolic events reported, indicating a potential safety benefit in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Utility of Bromocriptine in Acute Peripartum Cardiomyopathy. Badianyama, M., Das, PK., Gaddameedi, SR., et al.[2021]

Citations

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academic.oup.com

academic.oup.com/eurheartj/article/46/11/1017/7739744

Bromocriptine treatment and outcomes in peripartum ...

Among women with PPCM, bromocriptine treatment was associated with better maternal outcomes after 6 months and no increased risk of thromboembolic events.

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sciencedirect.com

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Efficacy and safety of bromocriptine in peripartum ...

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Bromocriptine as a Novel Therapeutic Agent ...

Recent studies have shown that adding bromocriptine to the treatment regimen of PPCM provides better clinical and echocardiographic outcomes.

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internationaljournalofcardiology.com

internationaljournalofcardiology.com/article/S0167-5273(25)00148-2/abstract

Efficacy and safety of bromocriptine in peripartum ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06250257

Bromocriptine in Dilated Cardiomyopathy Among Women ...

5 mg daily for 2 weeks, followed by 2.5 mg daily for 6 weeks) in severe PPCM patients demonstrated an improved clinical outcome with high LV recovery rate at 6 ...

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ahajournals.org

ahajournals.org/doi/10.1161/circulationaha.115.020491

Peripartum Cardiomyopathy | Circulation

Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes.

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Bromocriptine - StatPearls - NCBI Bookshelf - NIH

Peripartum cardiomyopathy: Bromocriptine is used off-label for peripartum cardiomyopathy (PPCM) in conjunction with standard heart failure ...