Treprostinil Combined With Tadalafil for Pulmonary Hypertension

NCT01302444 | Terminated Phase 4 Results DMC

• 1 other identifier: T2 Trial
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

treprostinil; pulmonary hypertension, tadalafil

Outcome Measures

Primary Outcomes (4)

• All Cause Mortality

  16 weeks

• Adverse Events Are no Greater Than With Treprostinil Infusion Alone

  16 weeks

• WHO Functional Class Will Improve or Remain Stable

  16 weeks

• Hospitalizations

  16 weeks

Secondary Outcomes (4)

• 6 Minute Walking Distance Change Will Improve

  16 weeks of therapy

• Tei Index Change by Transthoracic Echocardiography

  16 weeks of therapy

• Plasma BNP (Brain Natriuretic Peptide)Level Change

  16 weeks of therapy

• Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP)as Assessed by Transthoracic Echocardiography Using Doppler Ultrasound

  16 weeks

Study Arms (2)

Tadalafil

ACTIVE COMPARATOR

first 4 weeks are for adjusting treprostinil dose, then Tadalafil 40mg daily for 12 weeks, Group is randomly chosen from entire cohort

Drug: Tadalafil

Placebo

PLACEBO COMPARATOR

first 4 weeks for adjusting treprostinil dose, then Placebo for 12 weeks

Drug: Placebo

Interventions

Tadalafil DRUG

Tadalafil 40mg for 12 weeks

Also known as: Adcirca

Tadalafil

Placebo DRUG

Placebo for 12 weeks

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients 18-80 years of age
• World Health Organization Group 1 PAH
• Idiopathic PAH
• Heritable PAH
• PAH associated with connective tissue disease
• PAH associated with surgical repair of congenital left to right shunt
• PAH associated with anorectic drug use
• WHO functional Class III-IV
• minute walking distance \> 150-meters and \< 450 meters
• Right heart catheterization showing mean PAP (pulmonary arterial pressure)\> 25 mmHg and PCWP (pulmonary capillary wedge pressure) \< 15 mmHg within 6 months of study entry.

You may not qualify if:

• Pulmonary hypertension associated with
• a. Portal hypertension b. HIV infection c. Pulmonary venous hypertension defined as PCWP \> 15 mmHg d. Chronic lung disease defined as i. FEV1(forced expiratory volume at one second
• )/FVC (forced vital capacity) less than 0.65 ii. TLC \< 0.70 iii. Untreated Sleep Apnea with AHI (apnea-hypopnea index )\> 20 or hemoglobin oxygen saturation nadir \< 87% e. Chronic Thromboembolic Disease f. Sarcoidosis g. Pulmonary veno occlusive disease (PVOD)
• Concomitant use of nitrates (any form) either regularly or intermittently.
• Concomitant use of potent CYP3A inhibitors (e.g., ritonavir, ketoconazole, itraconazole)
• Vascular disease of the retina including retinitis pigmentosa, any sudden vision loss, including any damage to the optic nerve or NAION
• low blood pressure or high blood pressure that is not controlled
• Postural hypotension
• Inability to manage home infusion therapy
• Pulmonary vasodilator therapy with any phosphodiesterase inhibitor or endothelin receptor antagonist within 30 days of study entry
• Participation in a clinical investigational study within previous 30 days
• Renal failure defined as:
• estimated creatinine clearance \< 30 ml/min
• serum creatinine \> 2.5 mg/dl
• Subjects with liver function abnormalities (ALT \[Alanine Aminotransferase or AST (Alanine Aminotransferase ) \> 3 times the upper limit of normal at screening or at baseline) or chronic liver disease

Sponsors & Collaborators

• Rhode Island Hospital: lead
• United Therapeutics: collaborator

Study Sites (9)

Maine Medical Center

Portland, Maine, 04102, United States

Location

Tuft's New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham & Womens Hospital

Boston, Massachusetts, 02115, United States

Location

Saint Barnabas Health Care System, Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Weill Cornell Medical Center

New York, New York, 10021, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Related Links

• treprostinil

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary

Interventions

Tadalafil; Sugars

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Carbohydrates

Results Point of Contact

• Title: James R Klinger, MD
• Organization: Rhode Island Hospital

jklinger@lifespan.org

Study Officials

• James R Klinger, MD

  Rhode Island Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2011
• First Posted: February 24, 2011
• Study Start: March 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: July 26, 2013
• Results First Posted: July 18, 2013

Record last verified: 2012-04

Locations

US (9)