Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.

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 Overview

• Status: Unknown
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Tadalafil; Drug: Vardenafil

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Petach Tikva, Israel, 49100
    • Pulmonary Institute, Rabin Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Patients treated with epoprostenol (Flolan) will be given tadalafil (Cialis).	Drug: Tadalafil; Orally, titrated to maximum 20mg od; Other Names: Cialis
Experimental: 2; Patients receiving iloprost (Ventavis) will receive vardenafil (Levitra)	Drug: Vardenafil; Orally, titrated to 10 mg bid; Other Names: Levitra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Six minute walking distance	12 weeks
Level of pro-NT BNP	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Echo-derived parameters	12 weeks
Cardiopulmonary exercise test	12 weeks

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Principal Investigator: Mordechai R Kramer, MD, Rabin Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Anticipated): January 1, 2010

Study Registration Dates

• First Submitted: June 25, 2008
• First Submitted That Met QC Criteria: June 25, 2008
• First Posted (Estimate): June 26, 2008

Study Record Updates

• Last Update Posted (Estimate): June 26, 2008
• Last Update Submitted That Met QC Criteria: June 25, 2008
• Last Verified: May 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil; Vardenafil Dihydrochloride
• Other Study ID Numbers: RMC084936CTIL