Bromocriptine in the Treatment of Peripartum Cardiomyopathy

Study Overview
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Brief Summary
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Peripartum cardiomyopathy (PPCM) is a rare, but significant heart disease affecting young women in the puerperal period. Thus far, no specific treatment has been approved to treat this disease. PPCM has a wide spectrum of clinical manifestations ranging from mild heart failure to severe cardiomyopathy, cardiogenic shock and death. A significant proportion of survivors have persistent chronic heart failure leading to disabling symptoms and decreased quality of life. Animal studies have suggested that prolactin is central to the development of PPCM. Prolactin has pro-inflammatory and anti-angiogenic effects that may promote PPCM. Bromocriptine, a central dopamine agonist known to decrease prolactin levels, might thwart its deleterious effects in women suffering from PPCM. Following this rationale, bromocriptine should improve myocardial function in women suffering from PPCM and thus, improve cardiovascular outcomes and healthcare outcomes.

Official Title
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Bromocriptine in the Treatment of Peripartum Cardiomyopathy, A Bayesian Randomized Registry Trial

Conditions
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Peripartum Cardiomyopathy

Intervention / Treatment
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* Drug: Bromocriptine
* Other: Guideline-driven medical therapy (GDMT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years; Peripartum cardiomyopathy defined by the following criteria: Development of heart failure in the last month of pregnancy or within 5 months of delivery; Absence of an identifiable alternative cause of heart failure; Absence of recognizable heart disease prior to the last month of pregnancy; Left ventricular systolic dysfunction demonstrated by classic echocardiographic criteria, such as depressed ejection fraction; Recent onset of PPCM ( 1 month); Written informed consent. Exclusion Criteria: Hypersensitivity or contraindication to bromocriptine; Patients already taking bromocriptine for PPCM or for another indication; Cardiogenic shock before enrolment; Survival expected to be less than 1 year due to non-cardiovascular causes (eg. cancer); Participation to another investigational drug or investigational device study within 30 days prior to randomization (participation to registries is allowed); Patients who in the opinion of the investigator will not comply with specified drugs, or follow-up evaluation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bromocriptine + Guideline-driven medical therapy<br>In addition to heart failure treatment described above, patients will be administered bromocriptine 2.5 mg orally twice daily for 14 days, followed by 2.5 mg orally daily for 42 days. Although not a study procedure, we recommend anticoagulation with prophylactic doses of subcutaneous low-molecular weight heparin during the whole duration of bromocriptine therapy. | Drug: Bromocriptine<br> <br> Other: Guideline-driven medical therapy (GDMT)<br> <br> |
| Other: Guideline-driven medical therapy<br>New onset PPCM will be managed according to the principles of guideline-driven medical therapy for new-onset heart failure as per the position statement for treatment of PPCM published by the European Society of Cardiology (ESC) and the Canadian Cardiovascular Society (CCS) update on heart failure and pregnancy . The choices and administration of GDMT will be left at the discretion of the treating physician | Other: Guideline-driven medical therapy (GDMT)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE | MACE : A compose of death from cardiovascular causes, aborted sudden death, heart transplantation, mechanical circulatory support or hospitalization for cardiovascular causes. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death from cardiovascular causes |  | 5 years | 
| Left ventricular ejection fraction (LVEF) recovery | Recovery defined as : (proportion of patients with LVEF ≥ 54%) | 6 months | 
| All-cause mortality |  | 5 years | 
| Occurence of arrythmias | Arrhythmia : Number of participants with sustained ventricular tachycardia, ventricular fibrillation or new onset atrial fibrillation | 1 year | 
| Number of all-cause hospitalisation |  | 5 years | 
| Health-related quality of life (HRQoL) with the Kansas City Cardiomyopathy questionnaire (KCCQ) |  | 1 year | 
| Health-related quality of life (HRQoL) with the World Health Organization (WHO) quality of life questionnaire (WHOQOL-BREF) |  | 1 year | 
| Heart transplantation |  | 5 years | 
| Mechanical circulatory support |  | 1 year | 
| Number of hospitalisation for cardiovascular causes |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PPCM, Bromocriptine, Peripartum cardiomyopathy