Pulmonary Hypertension (PH) Associated with Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 19.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 19.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 19.0 Level: PT Classification code 10037400 Term: Pulmonar
Conditions
Interventions
Trade Name: INOmax 400ppm mol/mol inhalation gas
Product Name: iNO
Pharmaceutical Form: Pressurised inhalation
INN or Proposed INN: NITRIC OXIDE
CAS Number: 10102-43-9
Concentration unit: mg/kg/h mill
Sponsors
Bellerophon Pulse Technologies, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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. 4. 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 =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. 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: a) start of or increase in systemic oral corticosteroid therapy and/or b) hospitalization 5. Left ventricular dysfunction as measured by: a) Screening echocardiographic evidence of left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] moderate (i.e., > Grade 3), or c) 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 GFRCKD-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. 7. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: NAP;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: Visit 1 and visit 4 (after +/- 4 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes from baseline measured by HRCT with pulsed iNO and after dosing with pulsed iNO for 4 weeks in: - Blood vessel % and density on lobar level - Blood vessel % and density on lobar level compared among patients with emphysema, chronic bronchitis or combined emphysema and chronic bronchitis as assessed by HRCT - Total lung volume at TLC - Lobar volumes at TLC - Internal airflow distribution based on lobar expansion - Airway volume down to generation 8-10 at TLC - Computational Fluid Dynamics (CFD)-based resistance on lobar level - Ventilation/perfusion (V/Q) matching - Spirometry Changes from baseline to 4 weeks of pulsed iNO and after 2 weeks of withdrawal from pulsed iNO: - 6MWD - Borg CR10 Dyspnea and Leg Fatigue Score - PRO - Right Ventricular (RV) and Left Ventricular (LV) size and function, PAP as measured by 2D-echocardiogram with Doppler;Timepoint(s) of evaluation of this end point: Visit 1, Visit 2, Visit 3, Visit 4, Visit 5 | — |
Countries
Belgium
Contacts
Public ContactJan De Backer
FLUIDDA nv
Outcome results
None listed