Tadalafil for Sarcoidosis Associated Pulmonary Hypertension

Study Overview
=================
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

Official Title
-----------------
Tadalafil for Sarcoidosis Associated Pulmonary Hypertension

Conditions
-----------------
Pulmonary Hypertension

Intervention / Treatment
-----------------
* Drug: Tadalafil


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sarcoid Associated Pulm. Hypertension<br>Single-arm open-label proof of concept study of tadalafil in patients with sarcoidosis associated pulmonary hypertension. | Drug: Tadalafil<br>* 20mg/day for one month then 40mg/day for additional 4 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minute Walk Distance |  | Baseline, Week 8, Week 16, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting Oxygen Saturation | Percent oxygen saturation of hemoglobin as measured by pulse oximetry in the resting state. | Baseline, Week 24 | 
| Oxygen Desaturation During 6 Minute Walk Test | Change (decrease) in oxygen saturation from start of 6 minute walk to nadir during the 6 minute walk test | Baseline, Week 24 | 
| Maximum Borg Dyspnea Score During 6 Minute Walk Test | The modified Borg scale consists of a vertical scale labelled 0 to10 with corresponding verbal expressions of progressively increasing sensation (shortness of breath) intensity. 0 represents no dyspnea, and 10 is the highest level of perceived dyspnea. | Baseline, Week 8, Week 16, Week 24 | 
| Brain Natriuretic Peptide Level |  | Baseline, Week 8, Week 16, Week 24 | 
| Short Form-36 Global Score | SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. The global score is determined by taking an average of the individual domain scores. The global score range is from 0 (worst) to 100 (best). | Baseline, Week 8, Week 16, Week 24 | 
| St. George's Respiratory Questionnaire (SGRQ) Score | The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life) | Baseline, Week 8, Week 16, Week 24 | 
| Number of Participants With Change in WHO Functional Class (WHO FC) | The WHO functional classification ranges from I (patient's disease does not affect daily activities) to IV (patient's disease causes severe impairment). Higher scores indicate more severe impairment. | Baseline, Week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sarcoidosis Associated Pulmonary Hypertension