Treprostinil Combined With Tadalafil for Pulmonary Hypertension

Status:	Archived
Conditions:	High Blood Pressure (Hypertension)
Therapuetic Areas:	Cardiology / Vascular Diseases
Healthy:	No
Age Range:	Any
Updated:	7/1/2011
Start Date:	March 2011
End Date:	March 2013

Randomized Placebo Controlled Trial of Treprostinil Infusion Combined With Oral Tadalafil or Placebo in Pulmonary Arterial Hypertension

Objectives: To test whether the combined administration of the medications treprostinil(a
prostacycline therapy), and tadalafil(a PDE-5 Inhibitor therapy) is better than the
administration of treprostinil alone. This treatment would be offered to newly diagnosed
patients with pulmonary arterial hypertension who are on no treatment for this disease and
are deemed candidates for the medication treprostinil by their physician. The combination
therapy will be compared to single therapy with only treprostinil in a double-blind manner.

Current therapy is to begin one treatment, either a PDE5 inhibitor or a prostacycline,
depending on the severity of the patient's PAH disease and add additional therapies as
deterioration occurs. This treatment could add two agents initially.

Secondary objectives are: To improve pulmonary arterial pressures as measured through a
cardiac echocardiogram, improve the subject's 6minute walk distance, delaying the time to
clinical worsening, and lowering plasma BNP levels.

Research Procedures: To begin the administration of both treatments at the same time.

Time period is 16 weeks with a one- year follow-up. Cardiac Echocardiograms, clinic
physician exams, and lab work will be followed. Subjects will be between the ages of 18 -
75.

Background: Many cardiovascular diseases such as essential hypertension, coronary artery
disease and congestive heart failure respond better to combinations of vasoactive drugs,
than to therapy with a single agent. Three categories of pulmonary anti-hypertensive
medications have been developed over the last 20 years, but their effect on management of
PAH when used in combination are mostly unknown. Two of the pulmonary arterial hypertension
(PAH) drug groups are prostacyclines, and PDE5 inhibitors. Although the effects of
prostacyclins are mediated via cAMP and the effects of PDE5 inhibitors are mediated via
cGMP, there is considerable cross talk between these nucleotides suggesting that adequate
levels of both may be needed to maintain normal pulmonary vascular tone and cellular growth
responses.

Objective/Hypothesis: This proposal hypothesizes that increasing the levels of both
nucleotides (prostacyclines and PDE5 inhibitors), may be more efficacious in the treatment
of PAH than increasing either one alone.

Specific Aims: The primary objective of this study is to determine if the combination of
treprostinil infusion combined with tadalafil is more efficacious than treprostinil alone in
improving the change from baseline in the 6 minute walking distance after 16 weeks of
therapy.

Study Design: The proposed study is a multi-center, randomized, double blind, two cohort,
parallel group, and 16-week study with 1-year long-term follow-up. The study aims to
compare the efficacy of combination therapy with treprostinil infusion and tadalafil to
treprostinil infusion alone.

Study Population: All patients who have been newly diagnosed with PAH and who, after
consultation with their physician, have elected to be treated with treprostinil infusion
will be invited to participate. A total of 66 subjects will be sort to enroll.

Treprostinil dosing will follow a 4 week up-titration schedule with a target 4week dose of
8ng/kg/min minimum, followed by a 12 week randomized tadalafil period.

We found this trial at

sites

Maine Children's Medical Center

22 Bramhall Street
Portland, Maine 04102

from

Portland, ME