Trial document




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  DRKS00000407

Trial Description

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Title

Efficacy of bromocriptine on left ventricular function in women with peripartum cardiomyopathy (PPCM)

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Trial Acronym

EBRO-PC

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URL of the Trial

http://www.mh-hannover.de/ppcm.html

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Brief Summary in Lay Language

Peripartum cardiomyopathy (PPCM) is a rare and potentially life-threatening heart disease. It affects previously healthy women between the last month of pregnancy and six months after delivery. Experimental studies showed, that cleavage of the lactation hormone prolactin into a toxic subform (16kDa prolactin) plays a major role in the development and progression of PPCM. Pilot studies showed tha blocking of prolactin by bromocriptine, a medication used in the clinical area to stop lactation since a longtime, was beneficial to prevent onset of PPCM in patients with a high risk for the disease. Several healing attempts suggest that Bromocriptine may also be efficient in treatment of acute PPCM. The aim of the present study is to analyze whether blocking prolactin by bromocriptin is suited as a novel disease specific therapy to treate PPCM. Therefore a randomized multicenter trial is launched. In this multicentre trial involving 12 large hospital centres the efficacy of bromocriptine to treat acute PPCM in addition to standard heart failure therapy is evaluated. Sixty patients will be recruited to the study.

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Brief Summary in Scientific Language

Peripartum cardiomyopathy (PPCM) is considered to be a rare, but potentally life threatening disease of unknown origin. Previously healthy women within the last month of pregnancy and six months after delivery suffer from sudden heart insufficiency. The clinic represent that of a dilative cardiomyopathy and is treated according to the guidelines with ACE-inhibitors, beta-blockers, vasodilatives and diuretics. Despite optimal treatment 9-23% of the cases lead to terminal heart failure, additional 50% recover only partially. Ad risk factors advanced or young age of the mother, tocolysis, twin pregnancy, preeclampsia and cesarean section are discussed. After the incidence rate 300 in Germany could be expected.
The diagnosis is often made late since fatigue, dry cough and breathlessness are often misinterpreted. Even more specific symptoms like peripheral edema, arrhythmias and thrombembolies are associated with modifications after pregnancy (postpartum). The diagnosis is based on four criteria: (1) onset within the last month of pregnancy or 6 months after delivery, (2) absence of an identifiable cause of heart failure, (3) absence of recognizable heart disease, (4) left ventricular dysfunktion with ejection fraction (EF9<45%. Only echocardiography and/or magnetic resonance imaging (MRI) can confirm a diagnosis.
Little is known about the pathomechanism: elevated oxidative stress and hereby induced cleavage of the nursing hormone prolactin into a 16 kDa fragment plays a role. This affects microcirculation and metabolic modifications of the cardiomyocytes. The blockade of prolactin secretion with bromocriptine, a widely used substance to stop lactation, showed promising results. This new approach for a specific therapy of PPCM should be verified in this clinical study.
By detailed characterization of our study population we would like to specify risk factors and to identify biomarkers in our study population in order to establish a blood test for easy and rapid diagnosis.

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Organizational Data

  •   DRKS00000407
  •   2010/05/26
  •   2009/10/20
  •   yes
  •   Approved
  •   5230M, Ethikkommission der Medizinischen Hochschule Hannover
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Secondary IDs

  •   U1111-1114-9675 
  •   2007-003710-34 
  •   NCT00998556  (ClinicalTrials.gov)
  •   4034923 
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Health Condition or Problem studied

  •   PPCM: Peripartum Cardiomyopathy
  •   O99.4 -  Diseases of the circulatory system complicating pregnancy, childbirth and the puerperium
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Interventions/Observational Groups

  •   The control arm is treated for heart failure according to guidelines of the German Society for Cardiology (DGK) and the European Society of Cardiology (ESC)
  •   The treatment arm obtains in addition to standard therapy for heart failure Bromocriptine, 2 x 2.5mg/day for 2 weeks followed by 1 x 2.5mg/day for 6 weeks.
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   N/A
  •   [---]*
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Primary Outcome

Change in LVEF from baseline to 6 months follow-up as assessed by cardiac magnetic resonance imaging (MRI).

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Secondary Outcome

Combined endpoints of hospitalization for heart-failure, cardiac transplantation, and mortality during 6 months follow-up; individual components of the combined endpoint.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
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Recruitment

  •   Actual
  •   2010/06/30
  •   60
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1. 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: 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.
2. Written informed consent of the patient

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Exclusion Criteria

1. Preexisting cardiac disease (except PPCM which had complete resolution) in a previous pregnancy)
2. Any preexisting serious conditions
3. Previous cardiac surgery or percutaneous coronary intervention
4. History of alcohol and/or any other drug abuse
5. Contraindication to trial medication or one of its components
6. Concomitant therapy other than specified in the trial protocol
8. Expected low compliance
9. Concomitant participation in other clinical trials

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Addresses

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    • Medizinische Hochschule Hannover, Klinik für Kardiologie und Angiologie
    • Ms.  Prof. Dr. phil.  Denise  Hilfiker-Kleiner 
    • Carl-Neuberg-Straße 1
    • 30625  Hannover
    • Germany
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    • Medizinische Hochschule Hannover, Klinik für Kardiologie und Angiologie
    • Ms.  Prof. Dr. phil.  Denise  Hilfiker-Kleiner 
    • Carl-Neuberg-Straße 1
    • 30625  Hannover
    • Germany
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    • Medizinische Hochschule Hannover Klinik für Kardiologie und Angiologie
    • Ms.  Prof. Dr. phil.  Denise  Hilfiker-Kleiner 
    • Carl-Neuberg-Str. 1
    • 30625  Hannover
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2016/03/04
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Trial Publications, Results and other Documents

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