This is an Open Label, Pilot Study Testing the Safety and Efficacy of Inhaled Treprostinil (Tyvaso®) in the Treatment of Pulmonary Hypertension (PH) Associated with Chronic Obstructive Pulmonary Disease (COPD).
Subjects who meet all the following criteria are eligible for enrollment in the study:
- Subject must be between the ages of 30 and 80 years at the time of randomization.
- Clinical diagnosis of COPD (Gold Stage II-IV) must be established by accepted criteria.
- Diagnosis of pulmonary hypertension established by a historic RHC defined as a PAm >25 mm Hg, and a PCWP ≤18 mm Hg.
- Pulmonary hypertension WHO group 3 (Dana Point Classification) as defined above (PH-COPD)
- A minimum weight of 45 Kg and a minimum systolic blood pressure of >90 mmHg
- Must be able to perform a 6 minute walk test
- NYHA functional class of II, III or IV.
- Subject must be able to maintain O2 saturation of ≥ 88% at rest (with or without supplemental O2).
- Subjects must be treated with background therapy for COPD for a minimum of 1 month prior to consideration of enrollment. Adequate background therapy will include: 1) O2 therapy (LTOT) as required, at rest or with exertion, to maintain a PaO2 saturation greater then 88% for at least 18 hours/day, 2) The use of an inhaled long-acting beta agonist, 3) optimal use of short-acting beta agonists and anti-cholinergic inhalers or inhaled corticosteroids or oral steroids, as determined by the treating COPD physician. Stable therapy will include no changes to the dose or frequency of long-acting beta agonist or long-acting anti-cholinergic or inhaled or oral steroid therapy for the preceding 30 days. Adjustments to short-acting beta agonists or anti-cholinergic therapy will be permitted.
- Subject must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved ICF and must sign the form prior to the initiation of any study procedure.
Subjects who meet any of the following criteria are disqualified from enrollment:
- The presence of pulmonary venous hypertension defined as a PCWP of >18 mm Hg by RHC or left ventricular end diastolic pressure >18 mm Hg by left heart catheterization.
- Systemic hypotension with a SBP <90 mmHg.
- Gold Stage I COPD
- Weight <45 Kg.
- Absence of pulmonary hypertension, with a PAm <25 mm Hg at rest.
- Pulmonary hypertension (PAm ≥25 mmHg at rest) for reasons other than COPD, as determined by other studies at the discretion of the principal investigator. This would include, but is not limited to, the concomitant presence of thromboembolic disease (acute or chronic), untreated or inadequately treated obstructive sleep apnea (OSA), connective tissue disease such as systemic sclerosis or systemic lupus erythematosus (SLE), portal hypertension, HIV-1 infection, toxin exposure such as methamphetamine or anorexigen use, and other members of the Dana point classification I, II, IV and V .
- Patients with documented left ventricular dysfunction (LVEF<45%) as measured by echocardiography.
- Subject is pregnant or breastfeeding,
- History of non-compliance with other medical therapies,
- Participation in another clinical study involving a medication or device within 4 weeks before the screening study,
- Inability to perform the 6 minute walk test (6MWT),
- Recipient of a lung transplant,
- A requirement of greater than 9 l/min of O2 to maintain oxygen saturations greater than 88% at rest,
- Subject received chronic prostanoid therapy for PAH within 4 weeks prior to the screening visit. (chronic prostanoid use is considered >7 days of treatment).
- Any condition or treatment that, in the opinion of the investigator, places the subject at an unacceptable risk as a trial participant.