Clinical trial NCT01324999: Tadalafil for Sarcoidosis Associated Pulmonary Hypertension
Official title: Tadalafil for Sarcoidosis Associated Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pulmonary Hypertension
Keywords: Sarcoidosis Associated Pulmonary Hypertension
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
name: United Therapeutics
name: University of Cincinnati
First posted: 2011-03-29
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed to assess safety and efficacy of tadalafil in patients with Sarcoidosis Associated Pulmonary Hypertension.

Hypothesis: Tadalafil is safe and effective in treating pulmonary hypertension in patients with Sarcoidosis


Eligibility criteria: Inclusion Criteria:

* Biopsy proven sarcoidosis
* Mean pulmonary artery pressure \> 25 mmHg at rest or greater than 30 mmHg with exercise by right heart catheterization within 1 year prior to entry into study
* Pulmonary capillary wedge pressure ≤ 15 mmHg
* PVR values ≥ 3.0 Woods units
* Forced vital capacity (FVC) \> 40% predicted
* Forced expiratory volume in 1 second (FEV1) \> 40% predicted
* WHO functional class II or III
* Stable sarcoidosis treatment regimen for three months prior to entry into study
* 6 minute walk distance between 150-450 meters
* Stable dose of antihypertensive medications
* On no other medication to treat PAH (sildenafil, vardenafil, treprostinil, epoprostenol, iloprost, bosentan, ambrisentan) within one month prior to enrollment and during duration of the study
* Non-pregnant females

Exclusion Criteria:

* Exercise limitation related to a non-cardiopulmonary reason (e.g. arthritis)
* Severe systemic hypertension \> 170/95
* Severe systemic hypotension \< 90/50
* History of priapism
* Patients with congestive heart failure (left ventricular dysfunction) LVEF \< 45% by echocardiogram
* Anticipation by the investigator for escalation in sarcoidosis treatment during the course of the study
* Pulmonary hypertension related to etiology other than sarcoidosis (i.e. HIV, scleroderma, chronic thromboemboli)
* Use within 1 month of an sildenafil or vardenafil
* WHO functional class IV status
* Patients with severe other organ disease felt by investigators to impact on survival during the course of the study
* Subjects with liver function abnormalities (ALT or 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)
* History of hypersensitivity reaction or adverse effect related to tadalafil
* Pregnant or lactating women
* Concomitant use of nitrates (any form) either regularly or intermittently
* Concomitant use of potent CYP3A inhibitors (eg, ritonavir, ketoconazole, itraconazole)
* Any additional contraindications and precautions specified in the package inserts for Tadalafil (Adcirca) not listed above

Primary outcomes:
measure: 6 Minute Walk Distance
timeFrame: Baseline, Week 8, Week 16, Week 24
Secondary outcomes:
measure: Resting Oxygen Saturation
timeFrame: Baseline, Week 24
measure: Oxygen Desaturation During 6 Minute Walk Test
timeFrame: Baseline, Week 24
measure: Maximum Borg Dyspnea Score During 6 Minute Walk Test
timeFrame: Baseline, Week 8, Week 16, Week 24
measure: Brain Natriuretic Peptide Level
timeFrame: Baseline, Week 8, Week 16, Week 24
measure: Short Form-36 Global Score
timeFrame: Baseline, Week 8, Week 16, Week 24
measure: St. George's Respiratory Questionnaire (SGRQ) Score
timeFrame: Baseline, Week 8, Week 16, Week 24
measure: Number of Participants With Change in WHO Functional Class (WHO FC)
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Hubert J Ford, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ford HJ, Baughman RP, Aris R, Engel P, Donohue JF. Tadalafil therapy for sarcoidosis-associated pulmonary hypertension. Pulm Circ. 2016 Dec;6(4):557-562. doi: 10.1086/688775.