Trial Outcomes & Findings for Darusentan Effect on PET Uptake Heterogeneity (NCT NCT00738049)
NCT ID: NCT00738049
Last Updated: 2014-08-15
Results Overview
Markovian homogeneity analysis characterizes an image produced by a PET scan by examining the probability that a pixel with a given intensity will have a neighbor with a different intensity. The homogeneity index ranges from \>0 to 1, where a value near 0 represents an image with a high probability that neighboring pixels have intensity values that differ greatly, and a value near 1 represents an image with a high probability that neighboring pixels have similar intensity values.
COMPLETED
PHASE2
40 participants
0, 2, 4, and 6 weeks
2014-08-15
Participant Flow
Potential subjects who had undergone prior PET studies were contacted by mailings after a preliminary chart review. They received information about the study and were asked if they were interested in taking part in the study. If interested a screening visit was scheduled to determine if they met other inclusion/exclusion criteria.
After signing consent, study participants who met preliminary study criteria, were asked to come for the first PET scan. If rest homogeneity was too high by PET, the patient was excluded from randomization; otherwise the patient was randomized to receive placebo or study drug. 40 participants enrolled and 20 excluded by PET as explained above.
Participant milestones
| Measure |
Darusentan Then Placebo,
Patients were randomized to oral Darusentan 100mg for 14 days and then underwent cardiac PET imaging. They then received placebo for 14 days and underwent PET imaging, followed by a washout period of 14 days and completed the final cardiac PET scan. Patients and physicians were blinded to medication assignment.
|
Placebo, Then Darusentan 100mg
Patients were randomized to oral placebo for 14 days, then underwent PET imaging. Study patients then received Darusentan 100mg for 14 days. The patients underwent cardiac PET imaging followed by a 14 day washout period and final PET scan. Patients and physicians were blinded to medication assignment.
|
|---|---|---|
|
1st Intervention(14 Days)
STARTED
|
13
|
7
|
|
1st Intervention(14 Days)
COMPLETED
|
13
|
7
|
|
1st Intervention(14 Days)
NOT COMPLETED
|
0
|
0
|
|
2nd Intervention(14 Days)
STARTED
|
13
|
7
|
|
2nd Intervention(14 Days)
COMPLETED
|
13
|
7
|
|
2nd Intervention(14 Days)
NOT COMPLETED
|
0
|
0
|
|
Washout
STARTED
|
13
|
7
|
|
Washout
COMPLETED
|
13
|
7
|
|
Washout
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Darusentan Effect on PET Uptake Heterogeneity
Baseline characteristics by cohort
| Measure |
Group 1
n=13 Participants
Group 1 received oral Darusentan 100mg during Phase 1 then placebo during Phase 2.
|
Group 2
n=7 Participants
Group 2 received placebo during Phase 1 then oral Darusentan 100 mg during Phase 2.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0, 2, 4, and 6 weeksPopulation: Statistical analysis is exploratory, therefore not easily planned. A paired t-test with 40 subjects will provide approximately 89% power to test the null hypothesis of no change in the homogeneity number versus a two-sided alternative at alpha= 5%,if the true mean change is 0.15,e.g.,a homogeneity index of 0.5 at baseline and 0.65 after darusentan.
Markovian homogeneity analysis characterizes an image produced by a PET scan by examining the probability that a pixel with a given intensity will have a neighbor with a different intensity. The homogeneity index ranges from \>0 to 1, where a value near 0 represents an image with a high probability that neighboring pixels have intensity values that differ greatly, and a value near 1 represents an image with a high probability that neighboring pixels have similar intensity values.
Outcome measures
| Measure |
Baseline
n=20 Participants
All patients underwent a baseline assessment of Markovian homogeneity before receiving darusentan or placebo
|
Darusentan 100mg
n=20 Participants
All patients underwent a baseline assessment of Markovian homogeneity while taking darusentan
|
Baseline at Rest
All patients underwent a baseline assessment of resting flow before receiving darusentan or placebo
|
Baseline at Hyperemia
All patients underwent a baseline assessment of hyperemic flow before receiving darusentan or placebo
|
|---|---|---|---|---|
|
Change During Darusentan Treatment in the Markovian Homogeneity Number, a Value That Quantitates Myocardial Perfusion Heterogeneity
|
0.33 No units
Standard Deviation 0.04
|
0.39 No units
Standard Deviation 0.10
|
—
|
—
|
SECONDARY outcome
Timeframe: 0, 2, 4, and 6 weeksOutcome measures
| Measure |
Baseline
n=20 Participants
All patients underwent a baseline assessment of Markovian homogeneity before receiving darusentan or placebo
|
Darusentan 100mg
n=20 Participants
All patients underwent a baseline assessment of Markovian homogeneity while taking darusentan
|
Baseline at Rest
n=20 Participants
All patients underwent a baseline assessment of resting flow before receiving darusentan or placebo
|
Baseline at Hyperemia
n=20 Participants
All patients underwent a baseline assessment of hyperemic flow before receiving darusentan or placebo
|
|---|---|---|---|---|
|
Change During Darusentan Treatment in Absolute Flow at Rest and Hyperemia
|
0.65 cc/min/gm
Standard Deviation 0.13
|
1.97 cc/min/gm
Standard Deviation 0.54
|
0.50 cc/min/gm
Standard Deviation 0.10
|
2.03 cc/min/gm
Standard Deviation 0.56
|
SECONDARY outcome
Timeframe: 0, 2, 4, and 6 weeksCFR is calculated as the unitless ratio between hyperemic to resting flow
Outcome measures
| Measure |
Baseline
n=20 Participants
All patients underwent a baseline assessment of Markovian homogeneity before receiving darusentan or placebo
|
Darusentan 100mg
n=20 Participants
All patients underwent a baseline assessment of Markovian homogeneity while taking darusentan
|
Baseline at Rest
All patients underwent a baseline assessment of resting flow before receiving darusentan or placebo
|
Baseline at Hyperemia
All patients underwent a baseline assessment of hyperemic flow before receiving darusentan or placebo
|
|---|---|---|---|---|
|
Change During Darusentan Treatment in the Coronary Flow Reserve (CFR)
|
3.52 no units
Standard Deviation 0.80
|
3.04 no units
Standard Deviation 0.61
|
—
|
—
|
Adverse Events
Group 1
Group 2
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
K. Lance Gould, MD
University of Texas Medical School at Houston
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place