Trial Outcomes & Findings for Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan (NCT NCT00840463)

NCT ID: NCT00840463

Last Updated: 2020-05-19

Results Overview

The primary efficacy outcome will be Pulmonary Vascular Resistance.PVR will be calculated as \[(PA mean - wedge) / Cardiac Output\]

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 4 participants
• Primary outcome timeframe: Baseline and Four months
• Results posted on: 2020-05-19

Participant Flow

Recruitment occurred through the UTSW clinics. Recruitment difficulties arose and the study was halted due to poor recruitment

Participant milestones

Measure	Ambrisentan Ambrisentan: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).	Placebo Placebo: Sugar pill
Overall Study STARTED	3	1
Overall Study COMPLETED	2	1
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Ambrisentan Ambrisentan: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).	Placebo Placebo: Sugar pill
Overall Study Adverse Event	1	0

Baseline Characteristics

Safety and Efficacy Trial to Treat Diastolic Heart Failure Using Ambrisentan

Baseline characteristics by cohort

Measure	Ambrisentan n=3 Participants Ambrisentan: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).	Placebo n=1 Participants Placebo: Sugar pill	Total n=4 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Age, Categorical >=65 years	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Age, Continuous	62 years n=93 Participants	50 years n=4 Participants	59.5 years n=27 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Four months

The primary efficacy outcome will be Pulmonary Vascular Resistance.PVR will be calculated as [(PA mean - wedge) / Cardiac Output]

Outcome measures

Measure	Ambrisentan n=2 Participants Ambrisentan: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).	Placebo n=1 Participants Placebo: Sugar pill
Change in Pulmonary Vascular Resistance (Wood Units)	-0.75 wood units Interval -0.77 to -0.72	2.81 wood units Interval 2.81 to 2.81

PRIMARY outcome

Timeframe: 4 months

Freedom from clinically significant adverse events will be measure by determining the number free from CSAEs and those who developed CSAEs

Outcome measures

Measure	Ambrisentan n=3 Participants Ambrisentan: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).	Placebo n=1 Participants Placebo: Sugar pill
Safety Assessment-Number of Subjects Who Are Free and Those Who Developed Clinically Significant Adverse Events (CSAEs) Free from clinically significant AE	2 Participants	1 Participants
Safety Assessment-Number of Subjects Who Are Free and Those Who Developed Clinically Significant Adverse Events (CSAEs) Developed clinically significant AE	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Four months

subjects complete the 6 minute walk test to determine how far (in meters) they are able to walk in 6 minutes.

Outcome measures

Measure	Ambrisentan n=2 Participants Ambrisentan: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).	Placebo n=1 Participants Placebo: Sugar pill
Change in 6 Minute Walk Distance	-22 meters Interval -93.0 to 48.0	53 meters Interval 53.0 to 53.0

SECONDARY outcome

Timeframe: basline and 4 months

Change in functional class from baseline to month 4. This is graded from WHO FC I to FC IV. Assessment will be completed by an investigator on the study at every visit.

Outcome measures

Measure	Ambrisentan n=3 Participants Ambrisentan: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).	Placebo n=1 Participants Placebo: Sugar pill
Change in Functional Class Worsened	0 Participants	0 Participants
Change in Functional Class Improved	0 Participants	0 Participants
Change in Functional Class Stable	3 Participants	1 Participants

SECONDARY outcome

Timeframe: baseline 4 months

Population: note that there was no change in the SF-36 score (baseline to month 4) for the placebo arm hence the mean is not meaningful

Change between baseline and follow-up in the physical functioning items of the SF-36 questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health

Outcome measures

Measure	Ambrisentan n=2 Participants Ambrisentan: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).	Placebo n=1 Participants Placebo: Sugar pill
Change in Short Form-36 Physical Functioning	12.5 score on a scale Interval -10.0 to 35.0	0 score on a scale Interval 0.0 to 0.0

Adverse Events

Ambrisentan

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ambrisentan n=3 participants at risk Ambrisentan: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).	Placebo n=1 participants at risk Placebo: Sugar pill
Cardiac disorders Admission for heart failure	33.3% 1/3 • Number of events 1	0.00% 0/1

Other adverse events

Measure	Ambrisentan n=3 participants at risk Ambrisentan: Subjects will be initiated at 2.5 mg per day and increased to 5mg daily in 2 weeks and then 10mg daily if clinically tolerated (edema is controlled and symptoms are stable).	Placebo n=1 participants at risk Placebo: Sugar pill
Cardiac disorders Edema	66.7% 2/3 • Number of events 2	0.00% 0/1
Cardiac disorders Chest pain or tightness	66.7% 2/3 • Number of events 2	0.00% 0/1
Musculoskeletal and connective tissue disorders Gout	33.3% 1/3 • Number of events 1	100.0% 1/1 • Number of events 1

Additional Information

Kelly Chin

UT Southwestern

Phone: 214-645-1825

Email: kelly.chin@utsouthwestern.edu

Results disclosure agreements

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