PPCM: Effect of Bromocriptine on Left Ventricular Function in Women With Peripartum Cardiomyopathy

Sponsor

Hannover Medical School (Other)

Overall Status

Completed

CT.gov ID

NCT00998556

Collaborator

German Federal Ministry of Education and Research (Other)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, controlled clinical trial to evaluate the efficacy and safety of bromocriptine for improvement of left ventricular function of women with Peripartum cardiomyopathy (PPCM). A Multi center trial in Germany.

Condition or Disease	Intervention/Treatment	Phase
Peripartum Cardiomyopathy	Drug: Bromocriptine	Phase 2

Detailed Description

Peripartum cardiomyopathy (PPCM) is a serious life threatening heart disease of unknown etiology in previously healthy women. Only a minority of patients recovers completely while the majority of PPCM patients develop persistent ventricular dysfunction and may experience severe heart failure leading to cardiac transplantation. Thus, these young patients are very sick at a time when the newborn would need a healthy mother. Many of PPCM patients need lifelong treatment causing a large financial and social burden. Indeed, a better understanding of the disease and more efficient therapeutic options are urgently needed. To date, no specific therapy is available so that patients are treated by medical pharmacotherapy for heart failure.

Diagnosis of PPCM is usually made at advanced stages of the disease in severely symptomatic women but prognosis of affected women is poor with reported mortality rates of 15% and recovery in only 23% to 54% of PPCM patients despite optimal medical treatment. Therefore strategies are urgently needed to identify patients at risk and novel therapeutic approaches are required to improve poor prognosis of affected women.

The trial would establish a new specific therapeutic regimen for PPCM and the investigators can expect that such a novel approach would be rapidly adopted in the clinical management of this disease. Since the trial design follows state-of the-art guidelines, the investigators assume that bromocriptine would shortly be adopted into clinical guidelines of the German Cardiac Society, European Cardiac Society, and the American Heart Association.

Study Design

Study Type:

Interventional

Actual Enrollment :

64 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Bromocriptine on LV Function in Women With Peripartum Cardiomyopathy A Randomized, Controlled Clinical Trial to Evaluate the Efficacy and Safety of Bromocriptine for Improvement of Left Ventricular Function of Women With PPCM

Study Start Date :

Jun 1, 2010

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bromocriptine Patients randomized to the study medication have to take bromocriptine orally for the first 14 days at a dose of 5 mg/day (= 2 tablets, 1 in morning, 1 in the evening). From day 15 to day 56 they will take a dose of 2.5 mg (= 1 tablet) orally in the evening. The duration of the intervention is 8 weeks, thereafter the patients continue to be observed in the follow-up part of the study up to month 6. The study medication is taken on top of standard therapy for heart failure. Part of this therapy are ACE inhibitors. ACE inhibitors are potentially harmful for the baby when getting into the breast milk, as bromocriptine stops milk production, no additional drug is needed.	Drug: Bromocriptine Patients randomized to the study medication have to take bromocriptine orally for the first 14 days at a dose of 5 mg/day (= 2 tablets, 1 in morning, 1 in the evening). From day 15 to day 56 they will take a dose of 2.5 mg (= 1 tablet) orally in the evening. The duration of the intervention is 8 weeks. The study medication is taken on top of standard therapy for heart failure.
No Intervention: Control Group The control group will receive standard therapy for heart failure. Part of this therapy are ACE inhibitors. Since ACE inhibitors are potentially harmful for the baby when getting into the breast milk, it is necessary to stop lactation in the control group as well.To stop lactation, application of bromocriptine (2.5mg/day) for up to one week.

Arm

Intervention/Treatment

Experimental: Bromocriptine

Patients randomized to the study medication have to take bromocriptine orally for the first 14 days at a dose of 5 mg/day (= 2 tablets, 1 in morning, 1 in the evening). From day 15 to day 56 they will take a dose of 2.5 mg (= 1 tablet) orally in the evening. The duration of the intervention is 8 weeks, thereafter the patients continue to be observed in the follow-up part of the study up to month 6. The study medication is taken on top of standard therapy for heart failure. Part of this therapy are ACE inhibitors. ACE inhibitors are potentially harmful for the baby when getting into the breast milk, as bromocriptine stops milk production, no additional drug is needed.

Drug: Bromocriptine

No Intervention: Control Group

The control group will receive standard therapy for heart failure. Part of this therapy are ACE inhibitors. Since ACE inhibitors are potentially harmful for the baby when getting into the breast milk, it is necessary to stop lactation in the control group as well.To stop lactation, application of bromocriptine (2.5mg/day) for up to one week.

Outcome Measures

Primary Outcome Measures

Change in left ventricular ejection fraction (LVEF) from baseline to six months follow-up [6 months]
Change in left ventricular ejection fraction (LVEF) from baseline to six months follow-up as assessed by cardiac Magnetic Resonance Imaging (MRI) & Echocardiography

Secondary Outcome Measures

Combined endpoint of hospitalization for heart failure, eligibility for cardiac transplantation, cardiac transplantation, and mortality during 6 months follow-up [6 months]
Combined endpoint of hospitalization for heart failure, eligibility for cardiac transplantation, cardiac transplantation, and mortality during 6 months follow-up; individual components of the combined endpoint; adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Female subjects in the first 5 months postpartum with new onset of left ventricular (LV) dysfunction (LV ejection fraction ≤35% as assessed by echocardiography) using the internationally accepted criteria for PPCM 1: absence of an identifiable cause of heart failure, absence of recognizable heart disease prior to the last month of pregnancy and LV systolic dysfunction demonstrated by classical echocardiographic criteria.
Age equal or greater 18
Written informed consent of the patient

Exclusion Criteria:

Preexisting cardiac disease (except PPCM which had complete resolution in a previous pregnancy)
Any preexisting serious conditions
Previous cardiac surgery or percutaneous coronary intervention
History of alcohol and/or any other drug abuse
Contraindication to the planned therapy (e. g. hypersensitivity to trial medication or one of its components)
Concomitant therapy other than specified in the trial protocol such as products for treatment of fungal infections, psychotropic drugs, medication with the active substances diclofenace, verapamil or doxycycline.
Women with child bearing potency without effective contraception (i. e. implants, injectables, combined oral contraceptives, some IUDs or vasectomized partner) during the conduct of the trial. Patients using hormonal methods of contraception must be informed about possible influences of the study drug on contraception, in addition heart failure drugs may interfere with contraception. Patients will be counselled about the safest method to be used for contraception.
Expected low compliance (e.g. by travel distance to trial site)
Concomitant participation in other clinical trials

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hannover Medical School (MHH)	Hannover	Niedersachsen	Germany	30625

Sponsors and Collaborators

Hannover Medical School
German Federal Ministry of Education and Research

Investigators

Principal Investigator: Johann Bauersachs, Prof. Dr., Hannover Medical School, Hannover, Germany
Study Chair: Denise Hilfiker-Kleiner, Prof. Dr., Hannover Medical School, Hannover, Germany