Trial Outcomes & Findings for Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem (NCT NCT00319982)

Results Overview

The change in E' velocity (difference between final value - baseline value) was compared between participants who received diltiazem and those who received placebo to gauge treatment response. Please note that the total duration on treatment varied between study subjects to maximize time on treatment for the trial. Specifically, subjects that enrolled earliest had the longest duration of treatment; those who enrolled latest had the shortest duration of treatment with a minimum treatment duration of 1 year. All analyses examine the final study visit on treatment to the baseline visit.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

39 participants

Primary outcome timeframe

Baseline and final study visits

Results posted on

2015-04-07

Participant Flow

Participants were recruited from the HCM clinics at Brigham and Women's Hospital (Boston, MA), Boston Children's Hospital (Boston, MA), and Royal Prince Alfred Hospital (Sydney, Australia). Participants were recruited from 2006 through 2010.

Participant milestones

Participant milestones
Measure	I- Diltiazem (Active Arm) Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)
Overall Study STARTED	19	20
Overall Study COMPLETED	18	20
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	I- Diltiazem (Active Arm) Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	I- Diltiazem n=18 Participants Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo n=20 Participants Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)	Total n=38 Participants Total of all reporting groups
Age, Continuous	14.1 years STANDARD_DEVIATION 1.7 • n=5 Participants	17.3 years STANDARD_DEVIATION 2.1 • n=7 Participants	15.8 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants	19 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment Australia	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and final study visits

The change in E' velocity (difference between final value - baseline value) was compared between participants who received diltiazem and those who received placebo to gauge treatment response. Please note that the total duration on treatment varied between study subjects to maximize time on treatment for the trial. Specifically, subjects that enrolled earliest had the longest duration of treatment; those who enrolled latest had the shortest duration of treatment with a minimum treatment duration of 1 year. All analyses examine the final study visit on treatment to the baseline visit.

Outcome measures

Outcome measures
Measure	I- Diltiazem n=18 Participants Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo n=20 Participants Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)
Increase, Stability of, or Decrease in the Decline of Diastolic Function as Reflected by the Global Early Myocardial Relaxation (E') Velocity	-0.06 cm/sec (difference final-baseline) Standard Error 0.27	-0.21 cm/sec (difference final-baseline) Standard Error 0.42

SECONDARY outcome

Timeframe: Baseline through final study visits

Adverse events were compared between participants assigned to diltiazem and those assigned to placebo

Outcome measures

Outcome measures
Measure	I- Diltiazem n=18 Participants Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo n=20 Participants Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)
Safety and Tolerability of Diltiazem Treatment	10 Participants Reporting Adverse Events	12 Participants Reporting Adverse Events

SECONDARY outcome

Timeframe: Baseline and final study visits

Change in Value (Difference between Final and Baseline Visits)

Outcome measures

Outcome measures
Measure	I- Diltiazem n=18 Participants Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo n=20 Participants Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)
Impact of Diltiazem on Heart Rate	-4.9 beats/minute Standard Error 2.2	2.0 beats/minute Standard Error 2.6

SECONDARY outcome

Timeframe: Baseline and final study visits

Change in Left Ventricular End-Diastolic Diameter z-score (Final Value - Baseline Value)

Outcome measures

Outcome measures
Measure	I- Diltiazem n=18 Participants Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo n=20 Participants Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)
Left Ventricular Cavity Size	0.60 z-score units Standard Error 0.17	-0.53 z-score units Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline through final study visits

The number of participants who developed overt left ventricular hypertrophy during the duration of the trial was analyzed

Outcome measures

Outcome measures
Measure	I- Diltiazem n=18 Participants Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo n=20 Participants Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)
Development of Left Ventricular Hypertrophy	2 participants	2 participants

SECONDARY outcome

Timeframe: Duration of the trial

Adherence to study medication was assessed by pill count

Outcome measures

Outcome measures
Measure	I- Diltiazem n=18 Participants Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo n=20 Participants Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)
Adherence to Study Medication	83 percentage of pills taken Standard Deviation 10.8	90 percentage of pills taken Standard Deviation 6.6

SECONDARY outcome

Timeframe: Baseline and final study visits

Change in Value (Difference between Final and Baseline Visits)

Outcome measures

Outcome measures
Measure	I- Diltiazem n=18 Participants Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo n=20 Participants Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)
Impact of Diltiazem on Systolic Blood Pressure	-1.4 mmHg Standard Error 1.7	2.1 mmHg Standard Error 1.8

Adverse Events

I- Diltiazem

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

II- Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	I- Diltiazem n=18 participants at risk Diltiazem: Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period	II- Placebo n=20 participants at risk Placebo Comparator Placebo: Placebo comparator (double-blind allocation of study medication)
Cardiac disorders Shortness of Breath	33.3% 6/18 • Number of events 9 • Duration of Trial	5.0% 1/20 • Number of events 1 • Duration of Trial
Cardiac disorders Lightheadeness	16.7% 3/18 • Number of events 5 • Duration of Trial	25.0% 5/20 • Number of events 6 • Duration of Trial
Gastrointestinal disorders Nausea/GI distress	5.6% 1/18 • Number of events 1 • Duration of Trial	20.0% 4/20 • Number of events 4 • Duration of Trial
General disorders Fatigue	5.6% 1/18 • Number of events 1 • Duration of Trial	10.0% 2/20 • Number of events 2 • Duration of Trial
Nervous system disorders Headache	0.00% 0/18 • Duration of Trial	5.0% 1/20 • Number of events 2 • Duration of Trial
Cardiac disorders Chest Pain	16.7% 3/18 • Number of events 3 • Duration of Trial	5.0% 1/20 • Number of events 1 • Duration of Trial

Additional Information

Carolyn Ho, MD

Brigham and Women's Hospital

Phone: 617-732-5685

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place