Inhaled Nitric Oxide/INOpulse DS for Pulmonary Arterial Hypertension (PAH)

Completed · Phase 2 · Has a placebo group

Conditions studied: Pulmonary Arterial Hypertension, Pulmonary Hypertension

In brief

This is a Phase 2, Placebo Controlled, Double-Blind, Randomized, Clinical Study to Determine Safety, Tolerability and Efficacy of Pulsed, Inhaled Nitric Oxide (iNO) Versus Placebo as Add-on Therapy in Symptomatic Subjects with Pulmonary Arterial Hypertension (PAH).

Key facts

Study ID

NCT01457781

Run by

Bellerophon Pulse Technologies

People needed

80

Starts

2012-04-01

Expected to finish

2016-07-01

Last updated by the study team

2023-02-27

Who can join

Age: 16 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Signed informed consent form (ICF) (and assent as appropriate) prior to the initiation of any study mandated procedures or assessments
• A confirmed diagnosis of Pulmonary Hypertension Group 1 (PAH) who have either idiopathic PAH (IPAH), heritable PAH, anorexigen-induced PAH, associated PAH (APAH) with connective tissue disease (CTD), APAH with repaired simple congenital systemic to pulmonary shunt (i.e., atrial septal defect [ASD], ventricular septal defect [VSD] and/or patent ductus arteriosus [PDA]; complete repair at least 1 year prior to Screening) or APAH with human immunodeficiency virus (HIV)
• Confirmation of PAH diagnosis at the time of Baseline RHC according to the following definition: mPAP ≥ 25 mmHg at rest, with a concomitant mean pulmonary capillary wedge pressure (mPCWP), mean left atrial pressure (mLAP), or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg and a PVR ≥ 240 dynes.sec/cm-5
• 6MWD at least 100 meters and no greater than 450 meters
• The subject is receiving at least one approved PAH therapy and is clinically symptomatic from PAH (e.g., onset or increased dyspnea on exertion, dizziness, near-syncope, syncope, chest pain or peripheral edema)
• Background PAH medication doses (including calcium channel blockade if being used to treat PAH) must be stable for at least 12 weeks prior to Screening
• If on background conventional therapy (e.g., digoxin, diuretics, supplemental oxygen, anticoagulation), it must have been started at least 30 days prior to Screening and be on a stable dose for at least 30 days except for anticoagulation dose
• If previously treated with an endothelin receptor antagonist (ERA), phosphodiesterase-5 (PDE-5) inhibitor, prostacyclin or a prostacyclin analog and is no longer on said treatment at Screening (per inclusion criteria as above), subject must have been off said treatment for > 90 days at Screening
• If previously treated with a calcium channel blocker as treatment for PAH and is no longer on the calcium channel blocker treatment at Screening (per inclusion criteria as above), subject must have been off the calcium channel blocker treatment for > 90 days at Screening
• Age between 16 and 80 years (inclusive)
• Male height ≤ 200 cm (6'7") or Female height ≤ 210 cm (6'11")
• Subjects are willing and considered in the judgment of the Investigator able to use the INOpulse DS device continuously for up to 24 hours per day
• Females of childbearing potential must have a negative pre-treatment serum pregnancy test and must be on a reliable method of contraception (including double protection if appropriate, e.g., for subjects concurrently treated with bosentan therapy)

You may not qualify if…

• Subjects with known HIV infection within the past 2 years who have a history of or show any clinical or laboratory evidence of any opportunistic pulmonary disease (e.g., tuberculosis, Pneumocystis carinii pneumonia, or other pneumonias) at the time of Screening
• PAH associated with portal hypertension, untreated thyroid disorders, glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy
• Any subject with unrepaired congenital heart disease or repaired congenital heart disease other than the simple congenital to systemic shunts specified in the inclusion criteria, i.e., PAH associated with non-corrected simple congenital systemic-to-pulmonary shunts, corrected simple congenital systemic-to-pulmonary shunt with residual shunt post repair, or complex systemic-to- pulmonary shunts, corrected or non-corrected, or any other complex congenital heart disease, corrected or non-corrected
• PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, or pulmonary capillary hemangiomatosis
• Any subject with WHO PH Groups 2, 3, 4 or 5
• Left ventricular systolic dysfunction, i.e., left ventricular ejection fraction (LVEF) < 40% or left ventricular shortening fraction (LVSF) < 22%
• Left ventricular diastolic dysfunction, i.e., PCWP > 15 mmHg at rest or with exercise, acute volume loading or pharmacologic testing
• History of clinically significant cardiomyopathy or valvular heart disease (i.e., moderate or greater aortic insufficiency; moderate or greater aortic stenosis; or moderate or greater mitral valve disease)
• Clinically significant cardiac ischemic disease requiring use of nitrates, or hospital admission for acute coronary syndrome or intervention (percutaneous coronary intervention, coronary artery stent, coronary artery bypass surgery) within the past 90 days
• Down syndrome
• Any subject who develops a PCWP > 20 mmHg during AVT with iNO
• Systemic hypertension defined as systolic blood pressure (SBP) > 160 mmHg and/or diastolic blood pressure (DBP) > 100 mmHg persistent at Screening after a period of rest (treated or untreated)
• Systemic hypotension defined as SBP < 90 mmHg persistent at Screening after a period of rest
• Moderate to severe obstructive lung disease defined as both a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 70% and FEV1 < 65% of predicted value (bronchodilator administration prior to testing is optional; the test should be done within 3 years for all subjects with the exception of APAH/CTD which needs to be done within 6 months prior to Screening)
• Moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted; if TLC 60% to 70% predicted, a high resolution CT scan showing diffuse disease or more than mild patchy disease (done within 3 years for all subjects with the exception of APAH/CTD which needs to be done within 6 months prior to Screening)
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
• Estimated creatinine clearance < 30 mL/min (Cockcroft-Gault formula)
• Hemoglobin < 10 gm/dL at Screening or Baseline
• Acute or chronic physical impairment (other than dyspnea due to PAH) that would limit the ability to comply with study procedures or adherence to therapy, including carrying and wearing the INOpulse device per study protocol
• Pregnant or breast-feeding at Screening
• Administered L-arginine within 30 days prior to Screening
• Known concomitant life-threatening disease with a life expectancy less than 1 year
• Recently started (< 12 weeks prior to randomization) or planned cardiopulmonary rehabilitation program to start within the 16 week controlled study
• Atrial septostomy within 3 months of randomization
• Any subject with PAH who is treatment naïve or receiving any unapproved therapy as their only PAH treatment (including calcium channel blockade if the calcium channel blockade is the only treatment for the PAH)

Where it is running

• Arizona Pulmonary Specialists — Phoenix, Arizona, United States
• Allianz Research Institute, Inc. — Fountain Valley, California, United States
• University of California, San Francisco-Fresno — Fresno, California, United States
• West Los Angeles VA Healthcare Center — Los Angeles, California, United States
• David Geffen School of Medicine at UCLA — Los Angeles, California, United States
• Los Angeles Biomedical Research Institute at Harbor-UCLA Med Ctr — Torrance, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• University of Colorado Denver — Aurora, Colorado, United States
• South Denver Cardiology Associates P.C. — Littleton, Colorado, United States
• Christiana Care Health System — Newark, Delaware, United States
• University of Florida College of Medicine — Jacksonville, Florida, United States
• Cleveland Clinic Florida — Weston, Florida, United States
• Emory University Hospital-Emory Clinic — Atlanta, Georgia, United States
• University of Iowa Hospitals & Clinics — Iowa City, Iowa, United States
• University of Kansas Medical Center — Kansas City, Kansas, United States
• University of Kentucky Gill Heart — Lexington, Kentucky, United States
• Kentuckiana Pulmonary Associates — Louisville, Kentucky, United States
• LSUHSC-New Orleans — New Orleans, Louisiana, United States
• University of Maryland Medical Center — Baltimore, Maryland, United States
• Tufts Medical Center — Boston, Massachusetts, United States
• Boston University Medical Center/Boston University School of Medicine — Boston, Massachusetts, United States
• University of Michigan — Ann Arbor, Michigan, United States
• University of Minnesota, Cardiovascular Division — Minneapolis, Minnesota, United States
• Mayo Clinic — Rochester, Minnesota, United States
• University of Alabama at Birmingham — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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