Trial Outcomes & Findings for A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis (NCT NCT01042158)

Last Updated: 2017-09-12

Results Overview

Assessment of change in Right ventricular mass was done via standard volumetric cine images of the right heart at baseline and comparing it to that at the end of 36 weeks using Cardiac Magnetic Resonance Imaging studies.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

25 participants

Primary outcome timeframe

baseline and 36 weeks

Results posted on

2017-09-12

Participant Flow

This study had recruitment of patients from four centers, namely Johns Hopkins University, Stanford University, University of Texas Southwestern Medical Center, and the Cleveland Clinic. Patients who fulfilled the inclusion and exclusion criteria were screened for enrollment between August 25, 2011 and February 4, 2014.

This was a one arm study and patients were therefore selected based on the inclusion/exclusion criteria.

Participant milestones

Participant milestones
Measure	Tadalafil and Ambrisentan Upfront Therapy This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). tadalafil and ambrisentan upfront combination therapy: tadalafil 20 mg qd and ambrisentan 5 mg qd. Up-titration of study medications will occur at week 4 (ambrisentan 10 mgs daily and tadalafil 40 mg qd). If a subject experiences an intolerable adverse event as a result of an uptitration in the study drug dose, the dose of study drug maybe down titrated to 20 mg of tadalafil and/or 5mg of ambrisentan. If the subject is still experiencing an intolerable adverse event, then the investigator will withdraw the subject from the study.
Overall Study STARTED	25
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Tadalafil and Ambrisentan Upfront Therapy This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). tadalafil and ambrisentan upfront combination therapy: tadalafil 20 mg qd and ambrisentan 5 mg qd. Up-titration of study medications will occur at week 4 (ambrisentan 10 mgs daily and tadalafil 40 mg qd). If a subject experiences an intolerable adverse event as a result of an uptitration in the study drug dose, the dose of study drug maybe down titrated to 20 mg of tadalafil and/or 5mg of ambrisentan. If the subject is still experiencing an intolerable adverse event, then the investigator will withdraw the subject from the study.
Overall Study Physician Decision	1

Baseline Characteristics

A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tadalafil and Ambrisentan Upfront Therapy n=24 Participants This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). Tadalafil and ambrisentan upfront combination therapy: tadalafil 20 mg qd and ambrisentan 5 mg qd. Up-titration of study medications will occur at week 4 (ambrisentan 10 mgs daily and tadalafil 40 mg qd). If a subject experiences an intolerable adverse event as a result of an uptitration in the study drug dose, the dose of study drug maybe down titrated to 20 mg of tadalafil and/or 5mg of ambrisentan. If the subject is still experiencing an intolerable adverse event, then the investigator will withdraw the subject from the study.
Age, Continuous	59.9 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 36 weeks

Outcome measures

Outcome measures
Measure	Tadalafil and Ambrisentan Upfront Therapy n=24 Participants This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). tadalafil and ambrisentan upfront combination therapy: tadalafil 20 mg qd and ambrisentan 5 mg qd. Up-titration of study medications will occur at week 4 (ambrisentan 10 mgs daily and tadalafil 40 mg qd). If a subject experiences an intolerable adverse event as a result of an uptitration in the study drug dose, the dose of study drug maybe down titrated to 20 mg of tadalafil and/or 5mg of ambrisentan. If the subject is still experiencing an intolerable adverse event, then the investigator will withdraw the subject from the study.
Right Ventricular (RV) Mass Baseline	32.5 grams Interval 23.2 to 41.4
Right Ventricular (RV) Mass At 36 weeks	28.0 grams Interval 20.6 to 32.9

PRIMARY outcome

Timeframe: baseline 36 weeks

Change in Pulmonary Vascular Resistance (PVR) was ascertained via Right Heart Catheterization (RHC) measurement of the difference between the PVR at baseline and 36 weeks

Outcome measures

Outcome measures
Measure	Tadalafil and Ambrisentan Upfront Therapy n=24 Participants This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). tadalafil and ambrisentan upfront combination therapy: tadalafil 20 mg qd and ambrisentan 5 mg qd. Up-titration of study medications will occur at week 4 (ambrisentan 10 mgs daily and tadalafil 40 mg qd). If a subject experiences an intolerable adverse event as a result of an uptitration in the study drug dose, the dose of study drug maybe down titrated to 20 mg of tadalafil and/or 5mg of ambrisentan. If the subject is still experiencing an intolerable adverse event, then the investigator will withdraw the subject from the study.
Pulmonary Vascular Resistance (PVR) Baseline	6.9 Wood units Interval 4.0 to 12.9
Pulmonary Vascular Resistance (PVR) At 36 weeks	3.1 Wood units Interval 2.0 to 5.7

SECONDARY outcome

Timeframe: baseline and 36 weeks

The extent of displacement of the tricuspid valves, termed as Tricuspid Annular Plane Systolic Excursion (TAPSE) was measured using a trans-thoracic echocardiogram following Right heart catheterization.

Outcome measures

Outcome measures
Measure	Tadalafil and Ambrisentan Upfront Therapy n=24 Participants This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). tadalafil and ambrisentan upfront combination therapy: tadalafil 20 mg qd and ambrisentan 5 mg qd. Up-titration of study medications will occur at week 4 (ambrisentan 10 mgs daily and tadalafil 40 mg qd). If a subject experiences an intolerable adverse event as a result of an uptitration in the study drug dose, the dose of study drug maybe down titrated to 20 mg of tadalafil and/or 5mg of ambrisentan. If the subject is still experiencing an intolerable adverse event, then the investigator will withdraw the subject from the study.
Tricuspid Annular Plane Systolic Excursion (TAPSE) Baseline at week 0	2.2 cm Standard Deviation 0.12
Tricuspid Annular Plane Systolic Excursion (TAPSE) week 36	1.65 cm Standard Deviation 0.11

SECONDARY outcome

Timeframe: baseline and 36 weeks

patients were made to take a walk of normal speed to cover a distance in 6 minutes and distance covered was recorded. This was done at baseline (week o) and then repeated t 36 weeks.

Outcome measures

Outcome measures
Measure	Tadalafil and Ambrisentan Upfront Therapy n=24 Participants This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). tadalafil and ambrisentan upfront combination therapy: tadalafil 20 mg qd and ambrisentan 5 mg qd. Up-titration of study medications will occur at week 4 (ambrisentan 10 mgs daily and tadalafil 40 mg qd). If a subject experiences an intolerable adverse event as a result of an uptitration in the study drug dose, the dose of study drug maybe down titrated to 20 mg of tadalafil and/or 5mg of ambrisentan. If the subject is still experiencing an intolerable adverse event, then the investigator will withdraw the subject from the study.
6-minute Walk Distance Baseline (week 0)	343 meters Standard Deviation 131
6-minute Walk Distance Week 36	395 meters Standard Deviation 99

Adverse Events

Tadalafil and Ambrisentan Upfront Therapy

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tadalafil and Ambrisentan Upfront Therapy n=24 participants at risk This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). tadalafil and ambrisentan upfront combination therapy: tadalafil 20 mg qd and ambrisentan 5 mg qd. Up-titration of study medications will occur at week 4 (ambrisentan 10 mgs daily and tadalafil 40 mg qd). If a subject experiences an intolerable adverse event as a result of an uptitration in the study drug dose, the dose of study drug maybe down titrated to 20 mg of tadalafil and/or 5mg of ambrisentan. If the subject is still experiencing an intolerable adverse event, then the investigator will withdraw the subject from the study.
Cardiac disorders Stenosis of the left internal carotid artery, worsening shortness of breath, Right heart failure	12.5% 3/24 • Number of events 3 • through study completion, up to 36 weeks

Other adverse events

Adverse event data not reported

Additional Information

Paul Hassoun, MD

Johns Hopkins University

Phone: 410-614-5158

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place