- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03727451
A Dose Escalation Study to Assess the Safety and Efficacy of Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis or Sarcoidosis
A Dose Escalation Study to Assess the Safety and Efficacy of Pulsed, Inhaled Nitric Oxide in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis or Sarcoidosis on Long Term Oxygen Therapy Followed by an Optional Open-Label Long Term Extension Safety Study
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Florida
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Miami, Florida, United States, 33125
- University of Miami
-
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Ohio
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Cincinnati, Ohio, United States, 45219
- University of Cincinnati
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19140
- Temple University
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
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Virginia
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Falls Church, Virginia, United States, 22042
- Inova Heart and Lung Vascular Institute
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Washington
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Seattle, Washington, United States, 98195
- University of Washington Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Signed informed consent
A primary diagnosis of sarcoidosis as defined by the ATS/ERS/WASOG statement or pulmonary fibrosis associated with one of the following conditions:
2.1 Major IIPs (idiopathic interstitial pneumonias) diagnosed or suspected as one of the following:
- Idiopathic pulmonary fibrosis
- Idiopathic nonspecific interstitial pneumonia
- Respiratory bronchiolitis-interstitial lung disease
- Desquamative interstitial pneumonia
- Cryptogenic organizing pneumonia
- Acute interstitial pneumonia
- Rare IIPs diagnosis by one of the following:
- Idiopathic lymphoid interstitial pneumonia
- Idiopathic pleuroparenchymal fibroelastosis
- Unclassifiable idiopathic interstitial pneumonias
2.2 Chronic hypersensitivity pneumonitis
2.3 Occupational lung disease
2.4 Connective tissue disease with evidence of significant pulmonary fibrosis
Intermediate or high probability of PH by echocardiogram as assessed by local Radiologist/Investigator, or PH as determined by a right heart catheterization (RHC) within 5 years prior to Baseline with the following parameters:
- Pulmonary vascular resistance (PVR) ˃3 Wood Units (WU) (320 dynes.sec.cm-5)
- A left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg
- A mean pulmonary arterial pressure (mPAP) of ≥ 25 mmHg
- 6MWD ≥ 100 meters and ≤ 450 meters
- WHO Functional Class II-IV
- Forced Vital Capacity ≥ 40% predicted within last 6 weeks prior to screening
- Females of childbearing potential must have a negative pre-treatment pregnancy test (urine).
- Age between 18 and 85 years (inclusive)
- Clinically stable for at least 4 weeks prior to Baseline in the opinion of the Investigator
- If on therapy for their parenchymal lung disease and/or sarcoidosis, then the subject should be on a stable well-tolerated dose of the medication(s) for at least 4 weeks prior to enrollment.
Exclusion Criteria:
- Use of any type of PAH specific therapies
- Episodes of disease worsening within 3 months prior to Baseline
- Pregnant or breastfeeding females at Screening
- Administered L-arginine within 1 month prior to Screening
- Any subject who has been enrolled in any previous clinical study with inhaled NO administered through pulsed delivery
- On more than 6 L/min of oxygen at rest by nasal cannula for less than 4 weeks
- Evidence of any connective tissue disease with FVC > 60% in the last 6 months prior to screening unless there is evidence of moderate to severe fibrosis on CT scan in the opinion of the local radiologist/Investigator
- Evidence of clinically significant combined pulmonary fibrosis with emphysema (CPFE) if > 15% of lung fields by CT scan show evidence of emphysema in the opinion of the local radiologist/Investigator
- For subjects with sarcoidosis, clinically significant evidence of pulmonary fibrosis on CT scan in the opinion of the local radiologist/Investigator and FVC ≥80% predicted
- For subjects continuing on open label therapy, the concurrent use of the INOpulse device with a CPAP/BiPAP, or any other positive pressure device
Significant heart failure in the opinion of the Investigator
- LVEF<40% or
- PCWP on last RHC>15 mmHg (unless concurrent LVEDP <15 mmHg) or
- Significant diastolic dysfunction on echocardiogram
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: PH-Pulmonary Fibrosis
Part 1: 1st 4 subjects will be treated with iNO 30, 45, 75 mcg/kg IBW/hr 2nd 4 subjects will be treated with iNO 45, 75, 125 mcg/kg IBW/hr Part 2: Optional open label long term extension at the optimal dose as identified in Part 1 |
inhaled nitric oxide
Other Names:
|
EXPERIMENTAL: PH-Sarcoidosis
Part 1: 1st 4 subjects will be treated with iNO 30, 45, 75 mcg/kg IBW/hr 2nd 4 subjects will be treated with iNO 45, 75, 125 mcg/kg IBW/hr Part 2: Optional Open label long term extension at the optimal dose as identified in Part 1 |
inhaled nitric oxide
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measurement of mean PAP
Time Frame: During a single right heart catheterization procedure
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Mean pulmonary arterial pressure (mPAP) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr
|
During a single right heart catheterization procedure
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Measurement of PCWP
Time Frame: During a single right heart catheterization procedure
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Pulmonary capillary wedge pressure (PCWP) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr
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During a single right heart catheterization procedure
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Measurement of PVR
Time Frame: During a single right heart catheterization procedure
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Pulmonary vascular resistance (PVR) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr
|
During a single right heart catheterization procedure
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Measurement of CO
Time Frame: During a single right heart catheterization procedure
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Cardiac output (CO) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr
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During a single right heart catheterization procedure
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Change in 6MWD from Baseline to 16 Weeks
Time Frame: 16 weeks
|
Change in 6 minute walk distance
|
16 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence and Severity of Treatment Emergent Adverse Events
Time Frame: During a single right heart catheterization procedure
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Including adverse events related to device deficiency
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During a single right heart catheterization procedure
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Pulmonary Rebound
Time Frame: During a single right heart catheterization procedure
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Symptoms associated with acute withdrawal of iNO: systemic arterial oxygen desaturation, hypoxemia, bradycardia, tachycardia, systemic hypotension, shortness of breath, near-syncope and syncope
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During a single right heart catheterization procedure
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Distance Saturation Product (DSP)
Time Frame: 16 weeks
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Difference in DSP from baseline to Week 16 Difference in DSP from baseline to 16 weeks |
16 weeks
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Dyspnea
Time Frame: 16 weeks
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Difference in dyspnea as measured by UCSD Medical Center Pulmonary Rehabilitation Program Shortness of Breath Questionnaire on a scale from 0 (none at all) to 5 (maximal or unable to do because of breathlessness) from baseline to Week 16
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16 weeks
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Quality of Life Assessment
Time Frame: 16 weeks
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Difference in disease specific Quality of Life as measured by St. George's Respiratory Questionnaire
|
16 weeks
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Incidence of Adverse Events and Serious Averse Events
Time Frame: Through study completion; an average of 1 year
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Evaluation of adverse events and serious adverse events
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Through study completion; an average of 1 year
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Integral Distance Saturation Product (IDSP)
Time Frame: 16 weeks
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Difference in IDSP from baseline to Week 16
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16 weeks
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PULSE-PHPF-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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