Effect iNO on Functional Respiratory Imaging in Subjects With WHO Group 3 Pulmonary Hypertension With COPD on Oxygen

NCT03135860 | Terminated Early Phase 1 DMC

• 1 other identifier: PULSE-COPD-007
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this exploratory study is to examine the utility of high resolution computed tomography (HRCT) to measure changes in functional pulmonary imaging parameters as a function of long term iNO administrationusing the device INOpulse for 4 weeks in relation to Patient Reported Outcome (PRO) and exercise tolerance in subjects with WHO Group 3 PH associated with COPD on LTOT. Changes from baseline to 4 weeks of pulsed iNO and after 2 weeks of withdrawal from pulsed iNO will be evaluated.

Conditions

COPD; Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease

Keywords

Inhaled Nitric Oxide; COPD; Chronic Obstructive Pulmonary Disease; Idopathic Pulmonary Fibrosis; Long Term Oxygen Therapy (LTOT)

Outcome Measures

Primary Outcomes (1)

• change in lobar blood volume at total lung capacity with iNO and the change in lobar blood volume with iNO after 4 weeks of treatment with iNO as measured by HRCT.

  The primary endpoint in this exploratory study is the change in lobar blood volume at total lung capacity with iNO and the change in lobar blood volume with iNO after 4 weeks of treatment with iNO as measured by HRCT.

  After 4 weeks of treatment

Secondary Outcomes (11)

• Blood vessel % and density on lobar level

  after 4 weeks of treatment

• • Blood vessel % and density on lobal level compared among patients with emphysema, chronic bronchitis or combined emphysema and chronic bronchitis as assessed by HRCT

  after 4 week of treatment

• Total lung volume at TLC

  after 4 week of treatment

• Lobar volumes at TLC

  after 4 weeks of treatment

• Internal airflow distribution based on lobar expansion

  after 4 weeks of treatment

Study Arms (1)

Inhaled Nitric Oxide 30mcg/kg/IBW/hr

EXPERIMENTAL

Inhaled nitric oxide 30 mcg/kg IBW/hr NO will be administered through the InoPulse Device open label for 4 weeks

Drug: Inhaled Nitric Oxide 30mcg/kg IBW/hr

Interventions

Inhaled Nitric Oxide 30mcg/kg IBW/hr DRUG

Inhaled Nitric Oxide 30 mcg/kg IBW/hr will be administered through the INOPulse Device open label for 4 weeks

Also known as: iNO, NO,

Inhaled Nitric Oxide 30mcg/kg/IBW/hr

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 1. Male or female patient 2. A confirmed diagnosis of COPD by the Global initiative for chronic Obstructive Lung Disease (GOLD) criteria 3. Pulmonary hypertension will be defined as sPAP ≥ 38 mmHg as determined by echocardiogram (not obtained within ± 7 days of an exacerbation) within the past 12 months.
• \. Current or former smokers with at least 10 pack-years of tobacco cigarette smoking before study entry 5. Age ≥ 40 years, ≤ 85 years 6. A post-bronchodilatory FEV1/FVC \< 0.7 and a FEV1 \< 60% predicted (values obtained within 6 months prior to screening can be used unless obtained within ± 7 days of an exacerbation; otherwise, the test must be performed during screening) 7. Receiving LTOT for ≥ 3 months and ≥ 10 hours per day as determined by history 8. Females of childbearing potential must have a negative pre-scan urine pregnancy test 9. Signed informed consent prior to the initiation of any study mandated procedures or Assessments

You may not qualify if:

• \. Males who have the intention to father a child during the study. 2. A diagnosis of asthma or other non-COPD respiratory disease, in the opinion of the Investigator 3. Lack of patency of nares upon physical examination 4. Experienced during the last month an exacerbation requiring:
• start of or increase in systemic oral corticosteroid therapy and/or
• hospitalization 5. Left ventricular dysfunction as measured by:
• <!-- -->
• Screening echocardiographic evidence of left ventricular systolic dysfunction (left ventricular ejection fraction \[LVEF\] \< 40%), or
• Screening echocardiographic evidence of left ventricular diastolic dysfunction \>moderate (i.e., \> Grade 3), or
• Any history of pulmonary capillary wedge pressure (PCWP), left atrial pressure (LAP) or left ventricular end diastolic pressure (LVEDP) \> 18 mmHg as measured during cardiac catheterization within the past 6 months unless documented to have resolved by a subsequent cardiac catheterization 6. Renal impairment (i.e., an estimated GFR CKD-EPI \< 30 ml/min/1.73 m2) or history of renal failure using the equation:
• Men:
• crs\< 0.9 mg/dL: eGFRCKD-EPI = 141 × (crs /0.9)-0.411 × 0.993Age crs≥ 0.9 mg/dL: eGFRCKD-EPI = 141 × (crs /0.9)-1.209 × 0.993Age
• Woman:
• crs\< 0.7 mg/dL: eGFRCKD-EPI = 144 × (crs /0.7)-0.329 × 0.993Age crs≥ 0.7 mg/dL: eGFRCKD-EPI = 144 × (crs /0.7)-1.209 × 0.993Age where crs= Normal and elevated serum creatinine Subjects with possible compromised kidney function (i.e., Glomerular Filtration Rate estimated using the Modification of Diet in Renal Disease equation \[eGFR CKD-EPI\] between 30 and 60 ml/min/1.73 m2) may be enrolled provided the Radiology Department and Principal Investigator review the medical records of subjects with an eGFR CKD-EPI between 30 and 60 ml/min/1.73 m2 in order to confirm the contrast agent can be safely administered to these subjects and approval by both the Radiology Department and Principal Investigator must be obtained before enrolling these subjects.
• \. Known allergy to contrast media. 8. Clinically significant valvular heart disease that may contribute to PH, including mild or greater aortic valvular disease (aortic stenosis or regurgitation) and/or moderate or greater mitral valve disease (mitral stenosis or regurgitation), or status post mitral valve replacement 9. Use within 30 days of screening or current use of approved PH medications such as sildenafil or bosentan (use of Cialis® or Viagra® for erectile dysfunction is permitted) 10. Use of investigational drugs or devices within 30 days prior to enrollment into the study 11. Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study

Sponsors & Collaborators

• Bellerophon: lead

Study Sites (1)

Antwerp University Hospital

Edegem, 2650, Belgium

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Hypertension, Pulmonary

Interventions

Inosine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Ashika Ahmed, MD

  Bellerophon Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Exploratory Single Arm Study

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: May 1, 2017
• Study Start: October 1, 2016
• Primary Completion: August 21, 2017
• Study Completion: August 21, 2017
• Last Updated: February 21, 2023

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)