Bromocriptine in the Treatment of Peripartum Cardiomyopathy (BRO-HF)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Peripartum Cardiomyopathy
• Intervention / Treatment: Drug: Bromocriptine; Other: Guideline-driven medical therapy (GDMT)

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Marc Jolicoeur, MD, M.Sc., MHS; Phone Number: 3685 514-376-3330; Email: marc.jolicoeur@icm-mhi.org
• Study Contact Backup: Name: Marie-Gabrielle Lessard, RN, B.Sc.; Phone Number: 2094/2 Phone: 514-376-3330; Email: marie-gabrielle.lessard@icm-mhi.org

Study Locations

• Canada
  • Quebec
    • Monteal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age ≥ 18 years;

2. 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;
3. Recent onset of PPCM ( 1 month);
4. Written informed consent.

Exclusion Criteria:

1. Hypersensitivity or contraindication to bromocriptine;
2. Patients already taking bromocriptine for PPCM or for another indication;
3. Cardiogenic shock before enrolment;
4. Survival expected to be less than 1 year due to non-cardiovascular causes (eg. cancer);
5. Participation to another investigational drug or investigational device study within 30 days prior to randomization (participation to registries is allowed);
6. Patients who in the opinion of the investigator will not comply with specified drugs, or follow-up evaluation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

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
All-cause mortality		5 years
Death from cardiovascular causes		5 years
Left ventricular ejection fraction (LVEF) recovery	Recovery defined as : (proportion of patients with LVEF ≥ 54%)	6 months
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety adverse events	Safety adverse events: Combined occurence of venous thromboembolic disease, cardiac thrombus with embolic manifestation, myocardial infarction or cerebrovascular accident.	12 months

Collaborators and Investigators

• Sponsor: Montreal Heart Institute
• Collaborators: 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

Publications and helpful links

General Publications

• Azibani F, Sliwa K. Peripartum Cardiomyopathy: an Update. Curr Heart Fail Rep. 2018 Oct;15(5):297-306. doi: 10.1007/s11897-018-0404-x.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: October 12, 2015
• First Submitted That Met QC Criteria: October 27, 2015
• First Posted (Estimate): October 29, 2015

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: PPCM; Bromocriptine; Peripartum cardiomyopathy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Dopamine Agonists; Dopamine Agents; Hormone Antagonists; Antiparkinson Agents; Anti-Dyskinesia Agents; Bromocriptine
• Other Study ID Numbers: MP-33-2015-1874 (MP)