Trial Outcomes & Findings for Efficacy of Oral Bisoprolol on Heart Rate Reduction in Chinese Chronic Heart Failure Participants (NCT NCT03026088)

NCT ID: NCT03026088

Last Updated: 2020-01-29

Results Overview

Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

20 participants

Primary outcome timeframe

Baseline, Week 6

Results posted on

2020-01-29

Participant Flow

Participant milestones

Participant milestones
Measure
Bisoprolol
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Overall Study
STARTED
20
Overall Study
COMPLETED
0
Overall Study
NOT COMPLETED
20

Reasons for withdrawal

Reasons for withdrawal
Measure
Bisoprolol
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Overall Study
Study termination
20

Baseline Characteristics

Efficacy of Oral Bisoprolol on Heart Rate Reduction in Chinese Chronic Heart Failure Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Bisoprolol
n=20 Participants
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Age, Continuous
48.37 Years
STANDARD_DEVIATION 13.931 • n=5 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
Sex: Female, Male
Male
15 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
20 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline, Week 14

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 3, 10 and 18

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 14 and 26

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

LVEF was defined as the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat and it is used to measure the cardiac output for the heart. Ultrasound cardiogram performed to measure LVEF.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 14 and 26

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Left Ventricular End-Systolic Dimension was measured by Ultrasound cardiogram.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 14 and 26

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Left Ventricular End-diastolic Dimension was measured by Ultrasound cardiogram.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 14 and 26

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Interventricular septal thickness was measured by Ultrasound cardiogram.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 14 and Week 26

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Early to late ratio was measured by ultrasound cardiogram.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening (Week -2) up to Week 26

Population: The safety population included all participants who received at least one dose of study treatment.

Blood pressure (systolic and diastolic) measurement was taken at sitting position, with the elbow at the same level with the heart. Number of participants with clinically relevant systolic and diastolic blood pressure reported based on the assessment of the investigator.

Outcome measures

Outcome measures
Measure
Bisoprolol
n=20 Participants
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Number of Participants With Clinically Relevant Systolic and Diastolic Blood Pressure
0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: The safety population included all participants who received at least 1 dose of study treatment.

The NYHA classification assesses the severity of symptoms of heart failure. Here NYHA class of II - IV was assessed. NYHA II: Slight limitation of physical activity, comfortable at rest, but ordinary physical activity results in undue breathlessness, fatigue or palpitation. NYHA III: Marked limitation of physical activity, comfortable at rest, but less than ordinary activity causes undue breathlessness, fatigue or palpitation. NYHA IV: Unable to carry on any physical activity without discomfort, symptoms at rest can be present. If any physical activity is undertaken, discomfort increased.

Outcome measures

Outcome measures
Measure
Bisoprolol
n=20 Participants
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Number of Participants With New York Heart Association (NYHA) Class
Baseline: NYHA class II
10 Participants
Number of Participants With New York Heart Association (NYHA) Class
Baseline: NYHA class III
10 Participants
Number of Participants With New York Heart Association (NYHA) Class
Baseline: NYHA class IV
0 Participants
Number of Participants With New York Heart Association (NYHA) Class
Week 26: NYHA class II
2 Participants
Number of Participants With New York Heart Association (NYHA) Class
Week 26: NYHA class III
1 Participants
Number of Participants With New York Heart Association (NYHA) Class
Week 26: NYHA class IV
0 Participants
Number of Participants With New York Heart Association (NYHA) Class
Week 26: Not evaluated
17 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 26

Population: The safety population included all subjects who received at least one dose of study treatment.

Resting heart rate measurement was taken at sitting position for a continuous record of 3 minutes. Heartbeats in each minute was calculated and averaged to obtain the resting heart rate.

Outcome measures

Outcome measures
Measure
Bisoprolol
n=20 Participants
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Percentage of Participants With Resting Heart Rate Less Than 70 Beats Per Minute (Bpm) and More Than 55 Bpm
0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, end of treatment (Week 26)

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

MLHF questionnaire has 21 items. Questions assess the impact of frequent physical symptoms of heart failure and the effects of heart failure on physical and social functions. Each question had a possible score of 0 (best) to 5 (worst), for a total of 0 to 105. The higher the summed score, the worse is the impact of heart failure on a participant's quality of life.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, end of treatment (Week 26)

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Short Form Health Survey (SF-36), an instrument composed by 8 subscales: Physical Functioning, Physical Role Function, Bodily Pain, General Health, Vitality, Social Functioning, Emotional Role Function and Mental Health. The individual question items (Likert scale 0-4) are first summed for each item under the various sections. Then, those summary scores are then standardized on a scale between 0 and 1 using the mean and standard deviation of the actual scores and finally, weighted to a scale between 0 and 100. The items contributing to a scale are scored so that a higher score represents better health, and they are averaged together to create the scale score. Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and End of treatment (Week 26)

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

6-min walk test was a practical simple test that requires a 100-feet hallway but no exercise equipment or advanced training for technicians. Walking is an activity performed daily by all but the most severely impaired participants. This test measures the distance that a participant can quickly walk on a flat, hard surface in a period of 6 minutes.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to End of treatment (Week 26)

Population: The safety population included all participants who received at least one dose of study treatment.

Routine blood tests was performed to measure NT Pro-BNP. The normal range for NT Pro-BNP varies from 0 picograms/milliliter (pg/mL) (lower limit of normal value) -125 pg/mL (upper limit of normal value).

Outcome measures

Outcome measures
Measure
Bisoprolol
n=20 Participants
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Number of Participants With Abnormal Value of N-terminal Pro-B-type Natriuretic Peptide (NT Pro-BNP)
19 Participants

SECONDARY outcome

Timeframe: Baseline, week 6, 14 and end of treatment (Week 26)

Population: Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Holter monitor was used to measure heart rate (24 hour, day time, night time).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to end of treatment (Week 26)

Population: The safety population included all participants who received at least one dose of study treatment.

Holter monitor was used to diagnose arrhythmia.

Outcome measures

Outcome measures
Measure
Bisoprolol
n=20 Participants
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Number of Participants With Arrhythmia
0 Participants

SECONDARY outcome

Timeframe: Baseline, week 6, 14 and end of treatment (Week 26)

Population: The safety population included all participants who received at least 1 dose of study treatment.

Holter monitor was used to measure heart rate.

Outcome measures

Outcome measures
Measure
Bisoprolol
n=20 Participants
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Number of Participants With 24 Hour Heart Rate With More Than 70 Beats Per Minute (Bpm) and Less Than 55 Bpm
0 Participants

SECONDARY outcome

Timeframe: Up to Week 26

Population: The safety population included all participants who received at least 1 dose of study treatment.

MPR is used to assess the medicine compliance. MPR is defined as the actual drug number taken by the participants divided by the drug number should be taken by the participants according to the protocol. MPR between 80%-100% is defined as good compliance. Medication rate of less than (\<) 80% or greater than (\>)100% is defined as insufficient compliance.

Outcome measures

Outcome measures
Measure
Bisoprolol
n=20 Participants
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Number of Participants With Medicine Compliance Assessed by Medication Procession Ratio (MPR)
MPR: Good Compliance
18 Participants
Number of Participants With Medicine Compliance Assessed by Medication Procession Ratio (MPR)
MPR: Insufficient compliance
0 Participants
Number of Participants With Medicine Compliance Assessed by Medication Procession Ratio (MPR)
Not evaluated
2 Participants

SECONDARY outcome

Timeframe: Up to Week 26

Population: The safety population included all participants who received at least one dose of study treatment.

Number of participants with all-cause mortality, cardiac death, or re-admission due to heart failure was reported.

Outcome measures

Outcome measures
Measure
Bisoprolol
n=20 Participants
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Number of Participants With All Cause Mortality, Cardiac Death, or Re-admission Due to Heart Failure
All-cause mortality
1 Participants
Number of Participants With All Cause Mortality, Cardiac Death, or Re-admission Due to Heart Failure
Cardiac death
0 Participants
Number of Participants With All Cause Mortality, Cardiac Death, or Re-admission Due to Heart Failure
Re-admission due to heart failure
0 Participants

Adverse Events

Bisoprolol

Serious events: 4 serious events
Other events: 10 other events
Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure
Bisoprolol
n=20 participants at risk
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Cardiac disorders
Cardiac failure acute
5.0%
1/20 • Baseline up to Week 26
General disorders
Sudden death
5.0%
1/20 • Baseline up to Week 26
Nervous system disorders
Cerebral infarction
5.0%
1/20 • Baseline up to Week 26
Respiratory, thoracic and mediastinal disorders
Dyspnoea at rest
5.0%
1/20 • Baseline up to Week 26

Other adverse events

Other adverse events
Measure
Bisoprolol
n=20 participants at risk
Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Cardiac disorders
Angina pectoris
5.0%
1/20 • Baseline up to Week 26
Cardiac disorders
Sinoatrial block
5.0%
1/20 • Baseline up to Week 26
Cardiac disorders
Sinus bradycardia
5.0%
1/20 • Baseline up to Week 26
Gastrointestinal disorders
Diarrhoea
5.0%
1/20 • Baseline up to Week 26
Infections and infestations
Nasopharyngitis
5.0%
1/20 • Baseline up to Week 26
Infections and infestations
Upper respiratory tract infection 3 (15.0)
15.0%
3/20 • Baseline up to Week 26
Investigations
Blood uric acid increased
5.0%
1/20 • Baseline up to Week 26
Investigations
Weight increased
5.0%
1/20 • Baseline up to Week 26
Metabolism and nutrition disorders
Diabetes mellitus
5.0%
1/20 • Baseline up to Week 26
Metabolism and nutrition disorders
Hyperglycemia
5.0%
1/20 • Baseline up to Week 26
Skin and subcutaneous tissue disorders
Rash
5.0%
1/20 • Baseline up to Week 26
Vascular disorders
Hypertension
5.0%
1/20 • Baseline up to Week 26
Vascular disorders
Hypotension
5.0%
1/20 • Baseline up to Week 26

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place