Trial Outcomes & Findings for Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart (NCT NCT01798992)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

56 participants

Primary outcome timeframe

12 months

Results posted on

2023-11-29

Participant Flow

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.

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).

Participant milestones

Participant milestones
Measure	Non-failing Control Patients with normal ejection fraction who underwent a single myocardial biopsy and received no β-blocker therapy	Metoprolol Succinate Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months Metoprolol succinate	Metoprolol Succinate + Doxazosin 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	Carvedilol 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 Study STARTED	4	19	16	17
Overall Study COMPLETED	4	17	14	16
Overall Study NOT COMPLETED	0	2	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Metoprolol Succinate Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months Metoprolol succinate	Metoprolol Succinate + Doxazosin 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	Carvedilol 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 Study Administrative withdrawal	1	0	1
Overall Study Lost to Follow-up	1	1	0
Overall Study Insufficient biopsy tissue	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Non-failing Control n=4 Participants Patients with normal ejection fraction who underwent a single myocardial biopsy and received no β-blocker therapy	Metoprolol Succinate n=19 Participants Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months Metoprolol succinate	Metoprolol Succinate + Doxazosin n=16 Participants 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	Carvedilol n=17 Participants 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 n=56 Participants Total of all reporting groups
Age, Continuous	41.0 years STANDARD_DEVIATION 17.1 • n=93 Participants	45.9 years STANDARD_DEVIATION 13.6 • n=4 Participants	46.0 years STANDARD_DEVIATION 7.5 • n=27 Participants	44.9 years STANDARD_DEVIATION 15.1 • n=483 Participants	45.3 years STANDARD_DEVIATION 12.8 • n=36 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	4 Participants n=4 Participants	6 Participants n=27 Participants	5 Participants n=483 Participants	16 Participants n=36 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	15 Participants n=4 Participants	10 Participants n=27 Participants	12 Participants n=483 Participants	40 Participants n=36 Participants
Race/Ethnicity, Customized European Ancestry	4 participants n=93 Participants	15 participants n=4 Participants	9 participants n=27 Participants	13 participants n=483 Participants	41 participants n=36 Participants
Race/Ethnicity, Customized African Ancestry	0 participants n=93 Participants	1 participants n=4 Participants	4 participants n=27 Participants	0 participants n=483 Participants	5 participants n=36 Participants
Race/Ethnicity, Customized Hispanic	0 participants n=93 Participants	2 participants n=4 Participants	1 participants n=27 Participants	4 participants n=483 Participants	7 participants n=36 Participants
Race/Ethnicity, Customized Other	0 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants	0 participants n=483 Participants	3 participants n=36 Participants
Region of Enrollment United States	4 participants n=93 Participants	19 participants n=4 Participants	16 participants n=27 Participants	17 participants n=483 Participants	56 participants n=36 Participants
LV ejection fraction	58.8 % STANDARD_DEVIATION 7.4 • n=93 Participants	22.5 % STANDARD_DEVIATION 7.1 • n=4 Participants	28.5 % STANDARD_DEVIATION 8.7 • n=27 Participants	28.6 % STANDARD_DEVIATION 8.7 • n=483 Participants	28.6 % STANDARD_DEVIATION 11.9 • n=36 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Idiopathic dilated cardiomyopathy patients naive to beta-blocker therapy

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.

Outcome measures

Outcome measures
Measure	Metoprolol Succinate n=17 Participants Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months Metoprolol succinate	Metoprolol Succinate + Doxazosin n=14 Participants 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	Carvedilol n=16 Participants 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
Improvement in Left Ventricular Ejection Fraction (LVEF) at 12 Months	12 LVEF responders	10 LVEF responders	9 LVEF responders

SECONDARY outcome

Timeframe: 3 months

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.

Outcome measures

Outcome measures
Measure	Metoprolol Succinate n=17 Participants Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months Metoprolol succinate	Metoprolol Succinate + Doxazosin n=14 Participants 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	Carvedilol n=16 Participants 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
Improvement in LVEF at 3 Months	16 LVEF responders	10 LVEF responders	10 LVEF responders

SECONDARY outcome

Timeframe: 18 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Metoprolol Succinate n=17 Participants Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months Metoprolol succinate	Metoprolol Succinate + Doxazosin n=14 Participants 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	Carvedilol n=16 Participants 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
Composite of All-cause Mortality, Need for Heart Transplant or Need for Ventricular Assist Device.	1 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Other events: 0 other events

Deaths: 0 deaths

Carvedilol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Michael Bristow, MD PhD

University of Colorado, Denver

Phone: 303-724-5453

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place