Treprostinil Combined With Tadalafil for Pulmonary Hypertension (T2)
Objectives: To test whether the combined administration of the medications treprostinil(a prostacycline therapy), and tadalafil(a PDE-5 [ phosphodiesterase type 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 (pulmonary arterial hypertension) 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Randomized Placebo Controlled Trial of Treprostinil Infusion Combined With Oral Tadalafil or Placebo in Pulmonary Arterial Hypertension|
- All Cause Mortality [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Adverse Events Are no Greater Than With Treprostinil Infusion Alone [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
- WHO Functional Class Will Improve or Remain Stable [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Hospitalizations [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
- 6 Minute Walking Distance Change Will Improve [ Time Frame: 16 weeks of therapy ] [ Designated as safety issue: No ]
- Tei Index Change by Transthoracic Echocardiography [ Time Frame: 16 weeks of therapy ] [ Designated as safety issue: No ]
- Plasma BNP (Brain Natriuretic Peptide)Level Change [ Time Frame: 16 weeks of therapy ] [ Designated as safety issue: No ]
- Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP)as Assessed by Transthoracic Echocardiography Using Doppler Ultrasound [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2011|
|Study Completion Date:||March 2012|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Tadalafil
first 4 weeks are for adjusting treprostinil dose, then Tadalafil 40mg daily for 12 weeks, Group is randomly chosen from entire cohort
Tadalafil 40mg for 12 weeks
Other Name: Adcirca
Placebo Comparator: Placebo
first 4 weeks for adjusting treprostinil dose, then Placebo for 12 weeks
Placebo for 12 weeks
Other Name: sugar pill
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 (cyclic guanosine monophosphate) 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.
|United States, Maine|
|Maine Medical Center|
|Portland, Maine, United States, 04102|
|United States, Massachusetts|
|Tuft's New England Medical Center|
|Boston, Massachusetts, United States, 02111|
|Brigham & Womens Hospital|
|Boston, Massachusetts, United States, 02115|
|United States, New Jersey|
|Saint Barnabas Health Care System, Newark Beth Israel Medical Center|
|Newark, New Jersey, United States, 07112|
|United States, New York|
|Weill Cornell Medical Center|
|New York, New York, United States, 10021|
|Beth Israel Medical Center|
|new York, New York, United States, 10003|
|University of Rochester Medical Center|
|Rochester, New York, United States, 14642|
|United States, Rhode Island|
|Rhode Island Hospital|
|Providence, Rhode Island, United States, 02903|
|United States, Virginia|
|Inova Fairfax Hospital|
|Falls Church, Virginia, United States, 22042|
|Study Director:||James R Klinger, MD||Rhode Island Hospital|