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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01042158
• Date of registration: 04/01/2010
• Prospective Registration: No
• Primary sponsor: Johns Hopkins University
• Public title: A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis ATPAHSS
• Scientific title: A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
• Date of first enrolment: January 2010
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01042158
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

United States

Contacts

• Name: Paul Hassoun, MD
• Affiliation: Johns Hopkins University

Key inclusion & exclusion criteria

Inclusion Criteria:

- A right heart catheterization done at baseline with a mean pulmonary artery pressure
(mPAP) = 25mmHg, pulmonary artery wedge pressure (PAWP) = 15mmHg, and pulmonary
vascular resistance (PVR) =3 Woods units.

- Scleroderma defined as systemic sclerosis with diffuse or limited scleroderma meeting
the American College of Rheumatology (ACR) criteria (33). Cases will be included if
they meet clinical features that satisfy ACR criteria for a diagnosis of scleroderma
or the presence of three of five features of the CREST syndrome are identified; or
there is the presence of definite Raynaud's phenomenon, abnormal nail fold capillaries
typical of scleroderma and the presence of a specific scleroderma related
auto-antibody. Limited skin involvement is defined as skin tightening distal to elbows
and knees with or without facial involvement; and diffuse skin involvement, tightening
proximal to these joints or truncal involvement.

- Subjects will be older than 18 years of age with a diagnosis of PAH-SSc.

- Subjects will be NYHA functional class II or III.

- 6 minute walk distance = 100 meters and = 500 meters at screening and baseline.

- Negative urine pregnancy test for women of childbearing age at screening and baseline
visits.

- Ability and willingness to provide written informed consent

Exclusion Criteria:

- Right heart catheterization reveals evidence of pulmonary venous hypertension
(pulmonary capillary wedge pressure > 15 mm Hg).

- Significant chronic obstructive: Forced expiratory volume in 1 second to forced
expiratory volume ratio < 70% and a forced expiratory volume in 1 second less than 60%
of predicted.

- Interstitial lung disease

1. Based on a combination of pulmonary function tests and chest radiography.

2. Patients will be excluded if they have a total lung capacity less than 60% of
predicted and included if the total lung capacity was = 70%. Patients with a
total lung capacity between 60 and 70% of predicted are included if their
computed tomography scan demonstrates only minimal interstitial fibrosis

- Portal hypertension.

- Severe obstructive sleep apnea.

- Chronic thromboembolic disease.

- Positive antibodies to the human immunodeficiency virus.

- History of anorexigen use including fen-phen.

- Any other disease known to be associated with pulmonary hypertension.

- Subjects with other etiology for pulmonary hypertension besides PAH-SSc.

- Subjects with liver function abnormalities (ALT or Aspartate Aminotransferase (AST) >
3 times the upper limit of normal at screening or at baseline) or chronic liver
disease.

- Advanced kidney failure (GFR < 30 ml/min at screening or at baseline).

- Acute decompensation of underlying illness or hospitalization for pulmonary
hypertension within 4 weeks prior to enrollment.

- Prior chronic therapy with an endothelin-receptor antagonist, PDE V inhibitor, or a
prostacyclin analogue.

- History of hypersensitivity reaction or adverse effect related to ambrisentan or
tadalafil.

- History of implantable permanent pacemaker or any metallic objects in the body.

- Participation in a clinical study involving an investigational drug or device within
four weeks before the screening visit.

- Pregnant or lactating women.

- Concomitant use of nitrates (any form) either regularly or intermittently

- Concomitant use of potent Cytochrome P3A (CYP3A) inhibitors (eg, ritonavir,
ketoconazole, itraconazole)

- Any additional contraindications and precautions specified in the package inserts for
Tadalafil (Adcirca) and Ambrisentan (Letairis) not listed above.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Scleroderma Spectrum of Diseases

Connective Tissue Disease

Systemic Sclerosis

Pulmonary Hypertension

Intervention(s)

Drug: tadalafil and ambrisentan upfront combination therapy

Primary Outcome(s)

Right Ventricular (RV) Mass [Time Frame: baseline and 36 weeks]

Pulmonary Vascular Resistance (PVR) [Time Frame: baseline 36 weeks]

Secondary Outcome(s)

6-minute Walk Distance [Time Frame: baseline and 36 weeks]

Tricuspid Annular Plane Systolic Excursion (TAPSE) [Time Frame: baseline and 36 weeks]

Secondary ID(s)

TAD-PH-001

P50HL084946

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University of Texas

National Institutes of Health (NIH)

Stanford University

National Heart, Lung, and Blood Institute (NHLBI)

Eli Lilly and Company

United Therapeutics

The Cleveland Clinic

Results

• Results available: Yes
• Date Posted: 12/09/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01042158