Bromocriptine for Peripartum Cardiomyopathy

(REBIRTH Trial)

Recruiting at 63 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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the drug bromocriptine for peripartum cardiomyopathy?

Research shows that adding bromocriptine to standard heart failure treatment improved heart function in women with peripartum cardiomyopathy, increasing the heart's pumping ability by 11.37% and reducing mortality without causing blood clots. ^{1 2 3 4 5}

Is bromocriptine safe for use in humans?

Bromocriptine has been associated with serious side effects, including heart attacks, strokes, and severe blood vessel spasms, especially when used postpartum. It has been withdrawn from the market for postpartum lactation suppression due to these risks, and caution is advised, particularly for those with heart disease or high blood pressure. ^{3 6 7 8 9}

How is the drug bromocriptine unique in treating peripartum cardiomyopathy?

Bromocriptine is unique in treating peripartum cardiomyopathy because it works by blocking prolactin, a hormone that can cause heart damage in this condition, offering a novel approach compared to standard heart failure therapies. ^{2 3 4 10 11}

Research Team

Dennis McNamara

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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, 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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Utility of Bromocriptine in Acute Peripartum Cardiomyopathy. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Bromocriptine Use in Peripartum Cardiomyopathy: Review of Cases. [2020]

3. Australia pubmed.ncbi.nlm.nih.gov

Fatal myocardial infarction associated with bromocriptine for postpartum lactation suppression. [2019]

4. France 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]. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Bromocriptine treatment in patients with peripartum cardiomyopathy and right ventricular dysfunction. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Oral prednisolone supplement abolishes the acute adverse effects following initiation of depot bromocriptine therapy. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Bromocriptine related atypical vascular accidents postpartum identified through medicolegal reviews. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Severe cardiac dysrhythmia in patients using bromocriptine postpartum. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

The role of hypertension in bromocriptine-related puerperal intracranial hemorrhage. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Recovery from peripartum cardiomyopathy after treatment with bromocriptine. [2016]

11. Japan pubmed.ncbi.nlm.nih.gov

Effectiveness of bromocriptine treatment in a patient with peripartum cardiomyopathy. [2020]