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Pulmonary Arterial HypertensionPhase 2PAHNCT01457781

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

A Phase 2 study testing Inhaled Nitric Oxide 0.025 mg/kg IBW/hr delivered via INOpulse DS Device and Inhaled nitric oxide 0.075 mg/kg IBW/hr delivered via INOpulse DS Device in people with Pulmonary Arterial Hypertension and Pulmonary Hypertension, run by Bellerophon Pulse Technologies at 51 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 16 to 80 years
What is being tested?
Inhaled Nitric Oxide 0.025 mg/kg IBW/hr delivered via INOpulse DS Device and Inhaled nitric oxide 0.075 mg/kg IBW/hr delivered via INOpulse DS Device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
80 participants
Where
51 sitesin 2 countries
Study dates
Apr 2012to Jul 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 80 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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%
Show all 32Show fewer
  • 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)
  • Any subject who requires the use of a continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or other positive pressure devices to treat obstructive sleep apnea
  • Medical problem(s) likely to preclude completion of Part 1
  • Use of investigational drugs or devices within 30 days prior to enrollment into the study (other than acute vasodilator testing with iNO or IV epoprostenol)
  • Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study
  • Any condition other than the subject's PAH that, in that opinion of the investigator, affects their ability to perform the 6MWT
  • Refusal to follow the protocol, including the two RHCs in Part 1 and one RHC in Part 2
  • Unable to travel to the investigational site for all required study visits and for all additional visits per the judgment of the Investigator or Sponsor

Trial locations and contacts

51 sites in 2 countries.

51 sites in 2 countries

United States47 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University Hospital-Emory Clinic

    Atlanta, Georgia, 30322

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • University of Colorado Denver

    Aurora, Colorado, 80045

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-0006

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Boston University Medical Center/Boston University School of Medicine

    Boston, Massachusetts, 02118-2526

  • UC Health/University of Cincinnati

    Cincinnati, Ohio, 45267

  • University Hospitals Case Medical Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Ohio State University Martha Morehouse Medical Pavillion

    Columbus, Ohio, 43221

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Allianz Research Institute, Inc.

    Fountain Valley, California, 92708

  • University of California, San Francisco-Fresno

    Fresno, California, 93721

  • Baylor College of Medicine

    Houston, Texas, 77030

  • University of Iowa Hospitals & Clinics

    Iowa City, Iowa, 52242

  • University of Florida College of Medicine

    Jacksonville, Florida, 32209

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky Gill Heart

    Lexington, Kentucky, 40536

  • South Denver Cardiology Associates P.C.

    Littleton, Colorado, 80120

  • West Los Angeles VA Healthcare Center

    Los Angeles, California, 90073

  • David Geffen School of Medicine at UCLA

    Los Angeles, California, 90095

  • Kentuckiana Pulmonary Associates

    Louisville, Kentucky, 40202

  • Aurora St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • University of Minnesota, Cardiovascular Division

    Minneapolis, Minnesota, 55455

  • Intermountain Medical Center

    Murray, Utah, 84157

  • LSUHSC-New Orleans

    New Orleans, Louisiana, 70112

  • Beth Israel Medical Center

    New York, New York, 10003

  • Weill Cornell Medical Center

    New York, New York, 10021

  • Christiana Care Health System

    Newark, Delaware, 19713

  • University of Medicine and Dentistry of NJ

    Newark, New Jersey, 07103

  • Barnabas Health Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • South Oklahoma Heart Research LLC

    Oklahoma City, Oklahoma, 73135

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140

  • Arizona Pulmonary Specialists

    Phoenix, Arizona, 85012

  • Allegheny Singer Research Institute/Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • Legacy Medical Group - Pulmonary Clinic

    Portland, Oregon, 97210

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Sioux Falls Cardiovascular PC

    Sioux Falls, South Dakota, 57108

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • Los Angeles Biomedical Research Institute at Harbor-UCLA Med Ctr

    Torrance, California, 90509

  • Cleveland Clinic Florida

    Weston, Florida, 33331

Other trials in United States

Canada4 sites

  • Peter Lougheed Center

    Calgary, Alberta, T1Y614

  • ABACUS - University of Alberta Hospitals

    Edmonton, Alberta, T6G 2B7

  • London Health Sciences Centre

    London, Ontario, N6A 5W9

  • University Health Network - Toronto General Hospital

    Toronto, Ontario, M5G 2C4

Other trials in Canada

About this study

Official title: 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)

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).

Read the detailed description

Study to determine if inhaled nitric oxide (iNO) given through a special delivery device (INOpulse® DS) is safe and efficacious in treating Pulmonary Arterial Hypertension (PAH). Medical literature and clinical experience suggests that iNO at pulsed doses of 0.013 to 0.1 mg/kg per hour for 1 month to 2+ years appears safe and suggests efficacy for the treatment of pulmonary hypertension.

There are two parts to this study. In Part 1 (week 0 to week 16), the objectives are to determine the safety, tolerability, efficacy, and exploratory objectives of two different doses of iNO delivered by a pulsed delivery device in symptomatic subjects with PAH who remain symptomatic due to PAH on approved PAH monotherapy or combination approved PAH therapy. In Part 2 (week 17 to end of study Part 2 [EOS Part 2]), the objective is to compile data on the long-term effects of iNO on safety, tolerability, clinical and hemodynamic measures.

Being tested
Inhaled Nitric Oxide 0.025 mg/kg IBW/hr delivered via INOpulse DS Device, Placebo delivered via INOpulse DS Device, Inhaled nitric oxide 0.075 mg/kg IBW/hr delivered via INOpulse DS Device
Keywords
Inhaled nitric oxide, pulmonary arterial hypertension, pulmonary hypertension, PAH
Medical subject headings
Pulmonary Arterial Hypertension, Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Inhaled Nitric Oxide 0.025 mg/kg IBW/hr delivered via INOpulse DS DeviceCombination product

    Cohort 1: 0.025 mg/kg IBW/hr for up to 24 hours/day x 16 weeks (3.0 mg/L [2440 ppm] NO mini-cylinder; change q 24 hours) delivered via INOpulse DS Device and INOpulse DS nasal cannula

  • Placebo delivered via INOpulse DS DeviceCombination product

    Placebo 0.075 mg/kg IBW/hr for up to 24 hours/day x 16 weeks (Nitrogen N2, 99.999%) delivered via INOpulse DS Device and INOpulse DS nasal cannula

  • Inhaled nitric oxide 0.075 mg/kg IBW/hr delivered via INOpulse DS DeviceCombination product

    Cohort 2: 0.075 mg/kg IBW/hr for up to 24 hours/day x 16 weeks (6.0 mg/L [4880 ppm] NO mini-cylinder; change q 24 hours) delivered via INOpulse DS Device and INOpulse DS nasal cannula

Study groups in NCT01457781
Study groupRoleWhat they receive
0.025 mg inhaled nitric oxideActive comparatorInhaled nitric oxide (iNO) 0.025 mg/kg IBW/hr for up to 24 hours/day x 16 weeks (3.0 mg/L [2440 ppm] NO mini-cylinder; change q 24 hours) delivered via INOpulse® DS delivery device.
Receives: Combination Product: Inhaled Nitric Oxide 0.025 mg/kg IBW/hr delivered via INOpulse DS Device
0.075 mg inhaled nitric oxideActive comparatorInhaled nitric oxide (iNO) 0.075 mg/kg IBW/hr for up to 24 hours/day x 16 weeks (6.0 mg/L [4880 ppm] NO mini-cylinder; change q 24 hours) delivered via INOpulse® DS delivery device.
Receives: Combination Product: Inhaled nitric oxide 0.075 mg/kg IBW/hr delivered via INOpulse DS Device
placeboPlacebo comparatorPlacebo 0.075 mg/kg IBW/hr for up to 24 hours/day x 16 weeks* (99.999% Nitrogen [N2] mini-cylinder; change q 24 hours) delivered via INOpulse® DS delivery device.
Receives: Combination Product: Placebo delivered via INOpulse DS Device

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The primary endpoint is change in pulmonary vascular resistance (PVR) (dynes. sec/cm-5) from baseline to EOS Part 1.

    Change from Baseline to 18 weeks in PVR

    Measured: baseline to Week 16

Secondary outcomes (5)

  1. Change in 6 minute walk distance (6MWD) from baseline to EOS Part 1

    6MWT Change from Baseline to Week 16

    Measured: baseline to Week 16

  2. Time (in days) to first clinical worsening event (TTCW) from randomization to EOS Part 1

    Time (in days) to first clinical worsening event (TTCW) from randomization to EOS Part 1

    Measured: randomization to Week 16

  3. Change in World Health Organization (WHO) Functional Class from baseline to EOS Part 1

    WHO Functional Class Change from Baseline to Week 16

    Measured: baseline to Week 16

  4. Change in Borg Dyspnea Score (BDS) from baseline to EOS Part 1

    BDS change in Baseline to Week 16

    Measured: baseline to Week 16

  5. Change in patient reported outcome (PRO) scores by the SF-36 short form version 2 and the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) from baseline to EOS Part 1

    Patient Reported Outcome change from Baseline to Week 16

    Measured: baseline to Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Oct 2011 (estimated)
  2. Study startApr 2012
  3. Primary completionOct 2014
  4. Study completionJul 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01457781
Sponsor's protocol ID
IK-7001-PAH-201
Acronym
PAH
Status last verified
Jul 2022
First submitted
12 Oct 2011
Last updated
27 Feb 2023
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Inhaled Nitric Oxide 0.025 mg/kg IBW/hr delivered via INOpulse DS Device and Inhaled nitric oxide 0.075 mg/kg IBW/hr delivered via INOpulse DS Device in people with Pulmonary Arterial Hypertension and Pulmonary Hypertension, run by Bellerophon Pulse Technologies at 51 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The primary endpoint is change in pulmonary vascular resistance (PVR) (dynes. sec/cm-5) from baseline to EOS Part 1. (time frame: baseline to Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01457781.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2023.

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