BRO-HF: Bromocriptine in the Treatment of Peripartum Cardiomyopathy

Sponsor

Montreal Heart Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT02590601

Collaborator

Canadian Cardiovascular Society (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Peripartum Cardiomyopathy	Drug: Bromocriptine Other: Guideline-driven medical therapy (GDMT)	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bromocriptine + Guideline-driven medical therapy 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 Other: Guideline-driven medical therapy (GDMT)
Other: Guideline-driven medical therapy 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)

Arm

Intervention/Treatment

Active Comparator: Bromocriptine + Guideline-driven medical therapy

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

Other: Guideline-driven medical therapy (GDMT)

Other: Guideline-driven medical therapy

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)

Outcome Measures

Primary Outcome Measures

MACE [1 year]
MACE : A compose of death from cardiovascular causes, aborted sudden death, heart transplantation, mechanical circulatory support or hospitalization for cardiovascular causes.

Secondary Outcome Measures

Death from cardiovascular causes [5 years]
Left ventricular ejection fraction (LVEF) recovery [6 months]
Recovery defined as : (proportion of patients with LVEF ≥ 54%)
All-cause mortality [5 years]
Occurence of arrythmias [1 year]
Arrhythmia : Number of participants with sustained ventricular tachycardia, ventricular fibrillation or new onset atrial fibrillation
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]

Other Outcome Measures

Safety adverse events [12 months]
Safety adverse events: Combined occurence of venous thromboembolic disease, cardiac thrombus with embolic manifestation, myocardial infarction or cerebrovascular accident.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Montreal Heart Institute	Monteal	Quebec	Canada	H1T 1C8

Sponsors and Collaborators

Montreal Heart Institute
Canadian Cardiovascular Society

Investigators

Principal Investigator: Robert Avram, MD, Université de Montréal
Principal Investigator: Maxime Tremblay-Gravel, MD, MSc, Université de Montréal
Principal Investigator: Guillaume Marquis-Gravel, MD, MSc, Université de Montréal
Principal Investigator: Olivier Desplantie, MD CM, FRCPC, Université de Montréal
Principal Investigator: Anique Ducharme, MD FRCPC, Montreal Heart Institute