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Trial record 34 of 157 for:    Idiopathic Dilated Cardiomyopathy

Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart (BORG)

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ClinicalTrials.gov Identifier: NCT01798992
Recruitment Status : Completed
First Posted : February 26, 2013
Results First Posted : February 20, 2017
Last Update Posted : August 14, 2018
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
GlaxoSmithKline
AstraZeneca
Information provided by (Responsible Party):
University of Colorado, Denver

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Idiopathic Dilated Cardiomyopathy
Interventions Drug: Carvedilol
Drug: Metoprolol succinate
Drug: Metoprolol succinate + doxazosin
Enrollment 56
Recruitment Details Patients were recruited between 9/1/2000 and 3/1/2008 from outpatient general cardiology and heart failure specialty clinics at the University of Colorado Hospital and University of Utah Health Sciences Center.
Pre-assignment Details 65 patients met screening criteria and provided consent. Exclusions included personal preference (4), administrative reasons such as relocation (2), normalization of LVEF prior to assignment (2), and lack of central venous access (1).
Arm/Group Title Non-failing Control Metoprolol Succinate Metoprolol Succinate + Doxazosin Carvedilol
Hide Arm/Group Description Patients with normal ejection fraction who underwent a single myocardial biopsy and received no β-blocker therapy

Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months

Metoprolol succinate

Idiopathic dilated cardiomyopathy patients who were randomized to receive metoprolol succinate and doxazosin mesylate titrated to goals of 200 mg (metoprolol succinate) and 8 mg (doxazosin mesylate) by mouth daily for 18 months

Metoprolol succinate + doxazosin

Idiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months

Carvedilol

Period Title: Overall Study
Started 4 19 16 17
Completed 4 17 14 16
Not Completed 0 2 2 1
Reason Not Completed
Administrative withdrawal             0             1             0             1
Lost to Follow-up             0             1             1             0
Insufficient biopsy tissue             0             0             1             0
Arm/Group Title Non-failing Control Metoprolol Succinate Metoprolol Succinate + Doxazosin Carvedilol Total
Hide Arm/Group Description Patients with normal ejection fraction who underwent a single myocardial biopsy and received no β-blocker therapy

Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months

Metoprolol succinate

Idiopathic dilated cardiomyopathy patients who were randomized to receive metoprolol succinate and doxazosin mesylate titrated to goals of 200 mg (metoprolol succinate) and 8 mg (doxazosin mesylate) by mouth daily for 18 months

Metoprolol succinate + doxazosin

Idiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months

Carvedilol

Total of all reporting groups
Overall Number of Baseline Participants 4 19 16 17 56
Hide Baseline Analysis Population Description
Patients who gave informed consent and underwent baseline imaging and endomyocardial biopsy.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 19 participants 16 participants 17 participants 56 participants
41.0  (17.1) 45.9  (13.6) 46.0  (7.5) 44.9  (15.1) 45.3  (12.8)
[1]
Measure Description: Calculated using enrollment date - birthdate
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 19 participants 16 participants 17 participants 56 participants
Female
1
  25.0%
4
  21.1%
6
  37.5%
5
  29.4%
16
  28.6%
Male
3
  75.0%
15
  78.9%
10
  62.5%
12
  70.6%
40
  71.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 4 participants 19 participants 16 participants 17 participants 56 participants
European Ancestry 4 15 9 13 41
African Ancestry 0 1 4 0 5
Hispanic 0 2 1 4 7
Other 0 1 2 0 3
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants 19 participants 16 participants 17 participants 56 participants
4 19 16 17 56
LV ejection fraction   [1] 
Mean (Standard Deviation)
Unit of measure:  %
Number Analyzed 4 participants 19 participants 16 participants 17 participants 56 participants
58.8  (7.4) 22.5  (7.1) 28.5  (8.7) 28.6  (8.7) 28.6  (11.9)
[1]
Measure Description: Left ventricular ejection fraction = Stroke volume/End diastolic volume. Measured by single-photon emitted computed tomographic (SPECT) imaging or where not available, clinical multi-gated acquisition (MUGA) radionuclide ventriculography
1.Primary Outcome
Title Improvement in Left Ventricular Ejection Fraction (LVEF) at 12 Months
Hide Description The primary clinical outcome will be LVEF response at 12 months defined as an improvement in LVEF of ≥ 8% at 12 months or if not available, ≥5% at 3 months in the absence of an adverse clinical outcome. Data are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Idiopathic dilated cardiomyopathy patients naive to beta-blocker therapy
Arm/Group Title Metoprolol Succinate Metoprolol Succinate + Doxazosin Carvedilol
Hide Arm/Group Description:

Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months

Metoprolol succinate

Idiopathic dilated cardiomyopathy patients who were randomized to receive metoprolol succinate and doxazosin titrated to a goal of 200 mg and 8 mg by mouth daily for 18 months

Metoprolol succinate + doxazosin

Idiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months

Carvedilol

Overall Number of Participants Analyzed 17 14 16
Measure Type: Number
Unit of Measure: LVEF responders
12 10 9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metoprolol Succinate, Metoprolol Succinate + Doxazosin, Carvedilol
Comments The null hypothesis is that there is no difference in rate of LVEF improvement according to treatment group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.685
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title Improvement in LVEF at 3 Months
Hide Description A secondary outcome will be LVEF response at 3 months, defined as an improvement of ≥ 5% Data are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Metoprolol Succinate + Doxazosin Carvedilol
Hide Arm/Group Description:

Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months

Metoprolol succinate

Idiopathic dilated cardiomyopathy patients who were randomized to receive metoprolol succinate and doxazosin titrated to a goal of 200 mg and 8 mg by mouth daily for 18 months

Metoprolol succinate + doxazosin

Idiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months

Carvedilol

Overall Number of Participants Analyzed 17 14 16
Measure Type: Number
Unit of Measure: LVEF responders
16 10 10
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metoprolol Succinate, Metoprolol Succinate + Doxazosin, Carvedilol
Comments The null hypothesis is that there is no difference in rate of LVEF improvement according to treatment group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.071
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Composite of All-cause Mortality, Need for Heart Transplant or Need for Ventricular Assist Device.
Hide Description Clinical status at 18 months will be assessed at time of study completion, specifically for the composite outcome of all-cause mortality, need for heart transplant, or need for ventricular assist device. Outcomes are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
Idiopathic dilated cardiomyopathy patients randomized to different beta-blocker strategies. Data does not include non-failing controls, as these patients only underwent baseline evaluation with no treatment or follow-up, given that they did not have heart failure.
Arm/Group Title Metoprolol Succinate Metoprolol Succinate + Doxazosin Carvedilol
Hide Arm/Group Description:

Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months

Metoprolol succinate

Idiopathic dilated cardiomyopathy patients who were randomized to receive metoprolol succinate and doxazosin mesylate titrated to goals of 200 mg (metoprolol succinate) and 8 mg (doxazosin mesylate) by mouth daily for 18 months

Metoprolol succinate + doxazosin

Idiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months

Carvedilol

Overall Number of Participants Analyzed 17 14 16
Measure Type: Number
Unit of Measure: participants
1 0 0
4.Other Pre-specified Outcome
Title Change in Myocardial Gene Expression at 3 Months
Hide Description Changes in myocardial mRNA expression at 3 months compared to baseline using targeted quantitative polymerase chain reaction and genome wide microarray assays. Due to the large number of results genes interrogated (~ 20,000 genes), these results will instead be uploaded to the Gene Expression Omnibus.
Time Frame 3 months
Outcome Measure Data Not Reported
5.Other Pre-specified Outcome
Title Change in Myocardial Gene Expression at 12 Months
Hide Description Changes in myocardial mRNA expression at 12 months compared to baseline using targeted quantitative polymerase chain reaction and Affymetrix genome-wide microarray assays. Data are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
Time Frame 12 months
Outcome Measure Data Not Reported
6.Other Pre-specified Outcome
Title Change in Myocardial microRNA Expression at 3 Months
Hide Description Changes in myocardial microRNA expression at 3 months compared to baseline using an Affymetrix microRNA microarray assay. Data are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
Time Frame 3 months
Outcome Measure Data Not Reported
7.Other Pre-specified Outcome
Title Change in Myocardial microRNA Expression at 12 Months
Hide Description Changes in myocardial microRNA expression at 12 months compared to baseline using an Affymetrix microRNA microarray assay. Data are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
Time Frame 12 months
Outcome Measure Data Not Reported
Time Frame 18 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Metoprolol Succinate Metoprolol Succinate + Doxazosin Carvedilol
Hide Arm/Group Description

Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months

Metoprolol succinate

Idiopathic dilated cardiomyopathy patients who were randomized to receive metoprolol succinate and doxazosin titrated to a goal of 200 mg and 8 mg by mouth daily for 18 months

Metoprolol succinate + doxazosin

Idiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months

Carvedilol

All-Cause Mortality
Metoprolol Succinate Metoprolol Succinate + Doxazosin Carvedilol
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Metoprolol Succinate Metoprolol Succinate + Doxazosin Carvedilol
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/17 (0.00%)   0/14 (0.00%)   0/16 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Metoprolol Succinate Metoprolol Succinate + Doxazosin Carvedilol
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/17 (0.00%)   0/14 (0.00%)   0/16 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Michael Bristow, MD PhD
Organization: University of Colorado, Denver
Phone: 303-724-5453
EMail: Michael.Bristow@ucdenver.edu
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01798992     History of Changes
Other Study ID Numbers: 00-0242
2R01HL048013 ( U.S. NIH Grant/Contract )
First Submitted: February 22, 2013
First Posted: February 26, 2013
Results First Submitted: June 6, 2016
Results First Posted: February 20, 2017
Last Update Posted: August 14, 2018