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Bisoprolol in DMD Early Cardiomyopathy

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ClinicalTrials.gov Identifier: NCT03779646
Recruitment Status : Recruiting
First Posted : December 18, 2018
Last Update Posted : January 21, 2019
Sponsor:
Collaborators:
National Natural Science Foundation of China
Chinese Academy of Medical Sciences
Information provided by (Responsible Party):
Xiaoxiao Guo, Peking Union Medical College Hospital

Tracking Information
First Submitted Date  ICMJE December 14, 2018
First Posted Date  ICMJE December 18, 2018
Last Update Posted Date January 21, 2019
Actual Study Start Date  ICMJE January 16, 2019
Estimated Primary Completion Date July 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
Calculate the change of left ventricle global longitudinal strain in cardiac MR [ Time Frame: baseline and 12 months ]
Calculate the change of left ventricle global longitudinal strain in cardiac MR from baseline to 12months for each patients
Original Primary Outcome Measures  ICMJE
 (submitted: December 16, 2018)
To evaluate whether bisoprolol improve the left ventricle myocardial performance [ Time Frame: baseline and 12 months ]
Calculate the change of left ventricle global longitudinal strain in cardiac MR from baseline to 12months for each patients
Change History Complete list of historical versions of study NCT03779646 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
  • Calculate the change of left ventricular ejection fraction in cardia MR [ Time Frame: baseline and 12 months ]
    Calculate the change of left ventricular ejection fraction in cardia MR from baseline to 12months for each patients
  • Calculate the change of ventricle late gadolinium enhancement area in cardia MR [ Time Frame: baseline and 12 months ]
    Calculate the change of ventricle late gadolinium enhancement area in cardia MR from baseline to 12months for each patients
  • Calculate the change of the level of high-sensitivity cardiac troponin I [ Time Frame: baseline and 6months, 12 months ]
    Calculate the change of the level of high-sensitivity cardiac troponin I from baseline to 6months and 12months for each patients
  • Calculate the change of the level of NT-proBNP [ Time Frame: baseline and 6months, 12 months ]
    Calculate the change of the level of NT-proBNP from baseline to 6months and 12months for each patients
  • Calculate the change of E/A ratio assessed by echocardiography [ Time Frame: baseline and 12 months ]
    Calculate the change of diastolic dysfunction (E/A ratio) assessed by echocardiography from baseline to 12months for each patients
  • Change of the resting heart rate [ Time Frame: baseline and 6months, 12 months ]
    Calculate the change of the resting heart rate from baseline to 6months and 12months for each patients
Original Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2018)
  • To evaluate whether bisoprolol improve left ventricle ejection fraction [ Time Frame: baseline and 12 months ]
    Calculate the change of left ventricular ejection fraction in cardia MR from baseline to 12months for each patients
  • To evaluate whether bisoprolol reduce ventricle late gadolinium enhancement area [ Time Frame: baseline and 12 months ]
    Calculate the change of ventricle late gadolinium enhancement area in cardia MR from baseline to 12months for each patients
  • To evaluate whether bisoprolol improve the incidence of myocardial injury [ Time Frame: baseline and 6months, 12 months ]
    Calculate the change of the level of high-sensitivity cardiac troponin I from baseline to 6months and 12months for each patients
  • To evaluate whether bisoprolol improve the ventricle dysfunction [ Time Frame: baseline and 6months, 12 months ]
    Calculate the change of the level of NT-proBNP from baseline to 6months and 12months for each patients
  • To evaluate whether bisoprolol improve diastolic dysfunction [ Time Frame: baseline and 12 months ]
    Calculate the change of diastolic dysfunction assessment by echocardiography (E/A ratio) from baseline to 12months for each patients
  • Change of the resting heart rate [ Time Frame: baseline and 6months, 12 months ]
    Calculate the change of the resting heart rate from baseline to 6months and 12months for each patients
Current Other Pre-specified Outcome Measures
 (submitted: December 16, 2018)
  • Number of participants with All cause mortality, cardiac death, or hospitalized due to heart problem [ Time Frame: 12 months ]
    Number of Subjects with All cause mortality, cardiac death, or hospitalized due to heart problem at the end of study
  • Number of participants with bisoprolol-related adverse events as assessed by the following definition [ Time Frame: 12 months ]
    Bisoprolol treatment-related adverse events including the dizziness, bradyarrhythmia (resting heart rate lower than 55bpm),II and III degree atrioventricular block,hypotension
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Bisoprolol in DMD Early Cardiomyopathy
Official Title  ICMJE Bisoprolol for Early Cardiomyopathy in Duchenne Muscular Dystrophy: a Randomized, Controlled Trial
Brief Summary This study aimed to use cardiac magnetic resonance imaging (CMR) to evaluate the efficacy and safety of bisoprolol therapy for boys with Duchenne muscular dystrophy(DMD) and preserved ejection fraction. On top of angiotensin-converting enzyme inhibitor (ACEI) , half of the participants will receive bisoprolol in combination, while the other half will not receive any beta-blocker.
Detailed Description By the age of 20 years, almost all the patients with Duchenne muscular dystrophy(DMD) have experienced dilated cardiomyopathy (DCM), a condition that contributes significantly to their morbidity and mortality. Studies have shown ACEI to be an effective therapy for DMD boys with early cardiomyopathy. Although bisoprolol has been demonstrated as an effective neurohumoral drug for adult patients with DCM, few data exist concerning its safety and efficacy for the patients with DMD. The investigators hypothesize that the treatment with bisoprolol in addition to background ACEI therapy for 12 months in participants with DMD and early myocardial damage evident with late gadolinium enhancement and preserved ejection fraction, would blunt decline in left ventricular systolic performance.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is a randomized, controlled trial.Enrolled participants should receive a kind of ACEI drug for more than 1 month and the dose should be fixed. Then the participants were randomly assigned (1:1) to receive either bisoprolol or not any beta blocker.
Masking: Single (Outcomes Assessor)
Masking Description:
The investigator, care providers and participants will know whether the participants use the trial drug(bisoprolol) or not. But the outcome assessor who will analysis the results of the cardiac MR and echocardiography images from the participants will be blinded to the grouping situation.
Primary Purpose: Treatment
Condition  ICMJE
  • Duchenne Muscular Dystrophy
  • Cardiomyopathy, Dilated
Intervention  ICMJE Drug: Bisoprolol Fumarate
Bisoprolol was initiated at a dose of 1.25 mg every 24hr. At subsequent biweekly visits, the bisoprolol dose was increased 1.25mg progressively until a daily dose of 0.2mg/kg or the maximum tolerated dose (The rest heart rate <75bpm and systolic blood pressure <90mmHg) is achieved. If the participant feel dizziness or the rest heart rate below 60 bpm or systolic blood pressure below 85mmHg or there is any new onset contraindication to bisoprolol, the doctor will decide to return back to the previous dose or stop bisoprolol. Each time the dose is increased, the medication is administered in an outpatient clinic setting, with assessment of the participant's heart rate, blood pressure, symptoms and ECG. Once reach the target dose, the patients will be followed up every 8 weeks in an face-to-face or video visit. After 12 months , the participants will repeat cardiac MR besides heart rate, blood pressure, symptoms, ECG and brain natriuretic peptide(BNP), echocardiography records.
Study Arms  ICMJE
  • Experimental: bisoprolol fumarate
    In this arm, the participants will receive different dose of bisoprolol fumarate.
    Intervention: Drug: Bisoprolol Fumarate
  • No Intervention: Control
    In the control (no beta blocker) group, the patients not taking beta blocker will receive outpatient clinic or video visit every 8 weeks and provide their cardiac symptoms, heart rate, blood pressure and ECG. After 12 months , the patients will repeat cardiac MR besides heart rate, blood pressure, symptoms, ECG,BNP and echocardiography records.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 16, 2018)
42
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2022
Estimated Primary Completion Date July 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Older than(including) 7 years old
  • A definite diagnosis of DMD with muscle pathology confirming the expression of dystrophin lower than 5% and/or confirmed mutations in the DMD gene using a clinical accepted technique that completely defines the mutation.
  • Using ACEI or ARB for more than 1 month
  • Confirmed myocardial damage in one or more left ventricular segments evident by late gadolinium enhancement and preserved left ventricular systolic function(>45%) by cine cardiac MR in 45 days
  • Normal renal function
  • Holter and blood pressure shows no contraindication of using bisoprolol

Exclusion Criteria:

  • Having metal implanted in body
  • Having claustrophobia
  • Allergic to gadolinium
  • Complicated with other cardiovascular diseases
  • Medical history or Holter show bradyarrhythmia like II/III degree atrioventricular block, sick sinus syndrome etc.
  • Systolic blood pressure lower than 90mmHg or rest heart rate lower than 75bpm
  • Having COPD or asthma history
  • Having other complications: tumor, endocrine diseases
  • Having beta blockers therapy
  • Planned operation in the future 12 months
  • Allergic to bisoprolol
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 7 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Guo, Doctor +86-010-69155068 xiaoxiaoguopumch@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03779646
Other Study ID Numbers  ICMJE PekingUMCH-DMD
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Xiaoxiao Guo, Peking Union Medical College Hospital
Study Sponsor  ICMJE Peking Union Medical College Hospital
Collaborators  ICMJE
  • National Natural Science Foundation of China
  • Chinese Academy of Medical Sciences
Investigators  ICMJE Not Provided
PRS Account Peking Union Medical College Hospital
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP