Trial Outcomes & Findings for Ambrisentan in Single Ventricle (NCT NCT02080637)

NCT ID: NCT02080637

Last Updated: 2019-09-12

Results Overview

Plasma samples collected at 0-1,1-6,18-30 and 40-60 hours after administration of the first ambrisentan dose.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 16 participants
• Primary outcome timeframe: 0-1,1-6,18-30 and 40-60 hours
• Results posted on: 2019-09-12

Participant Flow

Participant milestones

Measure	Ambrisentan Oral ambrisentan 2.5 - 5 mg, single dose, once daily Ambrisentan: Once daily oral dosing	Placebo Oral placebo 2.5 - 5 mg, single dose, once daily Placebo
Overall Study STARTED	13	3
Overall Study COMPLETED	13	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ambrisentan in Single Ventricle

Baseline characteristics by cohort

Measure	Ambrisentan n=13 Participants Oral ambrisentan 2.5 - 5 mg, single dose, once daily Ambrisentan: Once daily oral dosing	Placebo n=3 Participants Oral placebo 2.5 - 5 mg, single dose, once daily Placebo	Total n=16 Participants Total of all reporting groups
Age, Continuous	35 months STANDARD_DEVIATION 6.7 • n=5 Participants	48 months STANDARD_DEVIATION 20.5 • n=7 Participants	37.4 months STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	2 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	1 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	13 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0-1,1-6,18-30 and 40-60 hours

Population: Five participants did not have all samples collected. Outcome measure not applicable to the Placebo group.

Plasma samples collected at 0-1,1-6,18-30 and 40-60 hours after administration of the first ambrisentan dose.

Outcome measures

Measure	Ambrisentan n=8 Participants Oral ambrisentan 2.5 - 5 mg, single dose, once daily Ambrisentan: Once daily oral dosing	Placebo Oral placebo 2.5 - 5 mg, single dose, once daily Placebo
Area Under the Curve for Ambrisentan Plasma Concentration	7871.46 ng*hr/mL Geometric Coefficient of Variation 36.96	—

PRIMARY outcome

Timeframe: baseline to 2 hours post ambrisentan administration

Population: One participant in the Ambrisentan group had central line removed early; Fontan pressures could not be measured.

Hemodynamic data, including Fontan pressures, common atrial pressures and saturations, will be collected at the specified timepoints. Pressures and saturations will be measured from existing monitoring lines. Standard Fick calculations will be used to calculate pulmonary vascular resistance (calculated as trans-pulmonary gradient [Fontan pressure - atrial pressure] / pulmonary blood flow [Qp]) and reported in Wood Units x m^2.

Outcome measures

Measure	Ambrisentan n=12 Participants Oral ambrisentan 2.5 - 5 mg, single dose, once daily Ambrisentan: Once daily oral dosing	Placebo n=3 Participants Oral placebo 2.5 - 5 mg, single dose, once daily Placebo
Change in Pulmonary Vascular Resistance Index	-0.5 WU*m^2 Standard Deviation 0.5	-0.2 WU*m^2 Standard Deviation 0.5

SECONDARY outcome

Timeframe: 0-96 hours post Fontan

Total chest tube drainage in mL in first 96hrs after Fontan

Outcome measures

Measure	Ambrisentan n=13 Participants Oral ambrisentan 2.5 - 5 mg, single dose, once daily Ambrisentan: Once daily oral dosing	Placebo n=3 Participants Oral placebo 2.5 - 5 mg, single dose, once daily Placebo
Amount of Chest Tube Drainage Post Fontan Operation	1325 milliliters Standard Deviation 531	1356 milliliters Standard Deviation 622

SECONDARY outcome

Timeframe: measured for the duration of the post-operative hospitalization or for 30 days, whichever is shorter

Chest tube duration will be calculated as the number of days from placement to removal.

Outcome measures

Measure	Ambrisentan n=13 Participants Oral ambrisentan 2.5 - 5 mg, single dose, once daily Ambrisentan: Once daily oral dosing	Placebo n=3 Participants Oral placebo 2.5 - 5 mg, single dose, once daily Placebo
Duration of Chest Tube Drainage Post Fontan Operation	6.54 days Standard Deviation 3.9	5.33 days Standard Deviation 1.5

Adverse Events

Ambrisentan

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ambrisentan n=13 participants at risk Oral ambrisentan 2.5 - 5 mg, single dose, once daily Ambrisentan: Once daily oral dosing	Placebo n=3 participants at risk Oral placebo 2.5 - 5 mg, single dose, once daily Placebo
Metabolism and nutrition disorders Electrolyte abnormalities	61.5% 8/13 • During hospitalization and for 30 days after administration of the last dose	66.7% 2/3 • During hospitalization and for 30 days after administration of the last dose
Blood and lymphatic system disorders Anemia	15.4% 2/13 • During hospitalization and for 30 days after administration of the last dose	0.00% 0/3 • During hospitalization and for 30 days after administration of the last dose
Respiratory, thoracic and mediastinal disorders Prolonged pleural effusion or chylothorax	23.1% 3/13 • During hospitalization and for 30 days after administration of the last dose	33.3% 1/3 • During hospitalization and for 30 days after administration of the last dose
Cardiac disorders Hypertension requiring treatment	7.7% 1/13 • During hospitalization and for 30 days after administration of the last dose	0.00% 0/3 • During hospitalization and for 30 days after administration of the last dose

Additional Information

Kevin Hill, M.D.

Duke University

Phone: 919-668-8305

Email: kevin.hill@duke.edu

Results disclosure agreements

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