Pulmonary arterial hypertension is a chronic disease of the lung blood vessels resulting in constriction and high pressures. Treatment is given with a variety of drugs including the prostanoid class (e.g. epoprostenol, iloprost and the phosphodiesterase 5 (PDE-5) inhibitors (e.g. sildenafil).

Although these drugs are known to be effective alone, little is known about combining them together in various combinations.

In this trial we will add a long-acting PDE-5 inhibitor to the treatment of patients with pulmonary arterial hypertension who currently are receiving only a prostanoid drug.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2010

Intervention(s) in this Clinical Trial

• Drug: Tadalafil
  • Orally, titrated to maximum 20mg od
• Drug: Vardenafil
  • Orally, titrated to 10 mg bid

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Patients treated with epoprostenol (Flolan) will be given tadalafil (Cialis).
• Experimental: 2
  • Patients receiving iloprost (Ventavis) will receive vardenafil (Levitra)

Primary Measures

• Six minute walking distance
  • Time Frame: 12 weeks
    Safety Issue?: No
• Level of pro-NT BNP
  • Time Frame: 12 weeks
    Safety Issue?: No

Secondary Measures

• Echo-derived parameters
  • Time Frame: 12 weeks
    Safety Issue?: No
• Cardiopulmonary exercise test
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• All patients must satisfy current diagnostic criteria for pulmonary artery hypertension based on their historical right heart catheter data (within 3 years of study enrollment): Mean PAP >25mmHg at rest or >30mmHg with exercise, by a PCWP<
• 15mmHg and by PVR >3 Wood Units.
• Currently stable for at least 3 months on prostanoid monotherapy (epoprostenol iv or iloprost inhaled).
• Willing and able to participate in all study follow-up procedures.
• New York Heart Association (NYHA) Class II-IV.
• Six minute walking distance between 100-450 meters at the baseline assessment.
• Women of child-bearing age must demonstrate adequate contraception or undergo a pregnancy test.
• Patients with congenital heart disease are eligible for inclusion.

Exclusion Criteria:

• Functional Class NYHA Class I.
• PAH due to chronic pulmonary thromboembolic disease, left heart disease, chronic lung diseases (VC or FEV1 < 60% of predicted) or chronic hypoxia.
• Acute intercurrent illness requiring hospital admission in the month proceeding screening.
• Any non-PAH medical condition likely to interfere with participation in evaluation of study endpoints, e.g. musculoskeletal disorders.
• Any uncontrolled or terminal non-PAH medical condition likely to interfere with completion of the study, according to the judgment of the study physician.
• Concomitant therapy with drugs known to interact adversely with the study drug.
• Chronic renal failure - creatinine clearance <50ml/min as calculated with the Cockcroft equation.
• Current participation in another clinical trial.
• Pregnancy or planned pregnancy during the study period.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Rabin Medical Center

Overall Clinical Trial Officials and Contacts

Mordechai R Kramer, MD Principal Investigator Rabin Medical Center  

Overall Contact: Mordechai R Kramer, MD 972-3-937-7221 kremerm@clalit.org.il

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00705588

Study ID Number: RMC084936CTIL

ClinicalTrials.gov Identifier: NCT00705588

Health Authority: Israel: Ministry of Health