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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02725372




Registration number
NCT02725372
Ethics application status
Date submitted
19/01/2016
Date registered
1/04/2016

Titles & IDs
Public title
Clinical Study of Pulsed, Inhaled Nitric Oxide Versus Placebo in Symptomatic Subjects With PAH
Scientific title
A Phase 3, Placebo Controlled, Double-Blind, Randomized, Clinical Study to Determine Efficacy, Safety, and Tolerability of Pulsed, Inhaled Nitric Oxide (iNO) Versus Placebo in Symptomatic Subjects With PAH (Part 1 and Part 2)
Secondary ID [1] 0 0
PULSE-PAH-004
Universal Trial Number (UTN)
Trial acronym
INOvation-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Inhaled Nitric Oxide 75 mcg/kg IBW/hr
Treatment: Drugs - Placebo

Experimental: Inhaled Nitric Oxide 75mcg/KgIBW/Hr - Part 1:

15Mcg/kg IBW/hr during Run-in Period dose titrated to Inhaled Nitric Oxide / 75mcg/KgIBW/Hr upon randomization to treatment arm.

Part 2: iNO 75 mcg/kg IBW/hr Open Label Treatment (Open Label Treatment - All Subjects)

Placebo comparator: Placebo - Part 1:

Placebo dose setting 15mcg/kg IBW/hr Run In Period / Placebo dose setting 75 mcg/kg IBW/hr treatment period


Treatment: Drugs: Inhaled Nitric Oxide 75 mcg/kg IBW/hr
Inhaled Nitric Oxide 15mcg/Kg IBW/hr for two week run in period dose titrated to Inhaled Nitric Oxide 75 mcg/kg IBW/hr at randomizationTreatment Period (Week 3 to Week 18)

Treatment: Drugs: Placebo
Part 1 Placebo arm: Inhaled Nitric Oxide 15mcg/Kg IBW/hrfor two week run in period dose titrated to Inhaled Nitric Oxide 75 mcg/kg IBW/hr at randomizationTreatment Period
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in 6-minute Walk Distance (6MWD) From Baseline (Randomization) to End of Treatment Period (Week 18)
Timepoint [1] 0 0
Change in 6MWD from Week 2 (2 weeks after randomization and run-in period) to Week 18 (end of blinded treatment period)
Secondary outcome [1] 0 0
Time (in Days) to First Clinical Worsening Event (TTCW)
Timepoint [1] 0 0
From Randomization to Week 18 (End of blinded treatment period)
Secondary outcome [2] 0 0
Number of Participants With an Improvement in World Health Organization Functional Class (WHO FC) Baseline (Randomization) to End of Treatment Period (Week 18)
Timepoint [2] 0 0
From Randomization to Week 18 (End of blinded treatment period)

Eligibility
Key inclusion criteria
1. Signed Informed Consent Form (and assent as appropriate) prior to the initiation of any study mandated procedures or assessments
2. A confirmed diagnosis of PAH Group 1 who have either idiopathic PAH (IPAH), heritable PAH, drug and toxin-induced PAH, associated PAH (APAH) with connective tissue disease (CTD), APAH with repaired simple congenital systemic to pulmonary shunt (i.e., atrial septal defect, ventricular septal defect and/or patent ductus arteriosus; complete repair at least 1 year prior to Screening), APAH with human immunodeficiency virus (HIV), or APAH with portal hypertension
3. Subjects receiving at least one PAH specific therapy (ERA or PDE-5 inhibitor, or inhaled, subcutaneous, or intravenous prostacyclin or a prostacyclin analog) with the same type of therapy for at least 3 months with stable dosing 4 weeks prior to Screening. (Subjects should be receiving optimal therapy according to the disease severity)
4. Subjects using oxygen therapy by nasal cannula for at least 4 weeks prior to Screening
5. PAH diagnosis confirmed by RHC within the previous 5 years, according to the following definitions:

* PVR = 400 dynes.sec.cm-5 (5 Wood units)
* mPAP = 25 mmHg
* PCWP or LVEDP = 15 mmHg
* Subjects who otherwise meet all the inclusion criteria and none of the exclusion criteria but have not undergone a RHC within the previous 5 years may be considered eligible for the study if they undergo a RHC and then meet the pulmonary hemodynamics criterion
6. 6MWD = 100 meters and = 450 meters prior to randomization
7. WHO Functional Class II-IV. Subjects with WHO Functional Class IV should be treated with prostacyclin or a prostacyclin analog (subcutaneous or intravenous), plus at least one additional PAH specific therapy (ERA or PDE-5), if available to the subject and reimbursed by health insurance
8. Age between 18 and 85 years (inclusive)
9. Willingness to use INOpulse delivery device for at least 12 hours per day
10. Willingness to continue on study drug until the subject has completed Week 18 assessments
11. Female subjects of childbearing potential must have a negative pre-treatment pregnancy test (serum or urine). All female subjects should take adequate precaution to avoid pregnancy.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects with known HIV infection who have a history within the past 3 months of any opportunistic pulmonary disease (e.g., tuberculosis, Pneumocystis carinii pneumonia, or other pneumonias) at the time of Screening 2. PAH associated with untreated thyroid disorders, glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy 3. Subjects with pulmonary conditions that may contribute to PAH including, but not limited to, chronic bronchiectasis, cystic fibrosis, or other pulmonary condition that the Investigator may deem to contribute to the severity of the disease or impair the delivery of iNO due to airway disease 4. Subjects receiving riociguat 5. Subjects receiving oral prostanoids as monotherapy 7. PAH associated with significant venous or capillary involvement, known or suspected pulmonary veno-occlusive disease, or pulmonary capillary hemangiomatosis 8. Any subject with WHO PH Groups 2, 3, 4 or 5 9. Subjects with any of the following cardiac abnormalities:

a. Underlying cardiomyopathy or clinically significant aortic or mitral valve disease in the opinion of the investigator b. Left ventricular systolic dysfunction (LVSD), i.e., left ventricular ejection fraction (LVEF) < 40% or left ventricular shortening fraction (LVSF) < 22%, as determined by local reading c. Current symptomatic coronary artery disease, myocardial infarction within 1 year, or any coronary artery interventions within 6 months 10. 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) 11. Subjects with a history of deep vein thrombosis, pulmonary embolism/infarction or prothrombotic disorder must have had chronic thromboembolic pulmonary hypertension (CTEPH) excluded by ventilation/perfusion lung (V/Q) scan 12. Severe obstructive lung disease defined as both a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 70% and FEV1 < 55% of predicted value 13. 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 14. Any subject who develops or has developed a PCWP > 20 mmHg during acute vasodilator testing (AVT) 15. Systemic hypotension defined as SBP < 90 mmHg persistent at Screening after a period of rest 16. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C 17. On dialysis 18. 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 (i.e., 6MWT), including carrying and wearing the pulsed delivery device per study protocol, or medical problem(s) likely to preclude completion of the study 19. Pregnant or breastfeeding females at Screening 20. Administered L-arginine within 1 month prior to Screening 21. Known concomitant life-threatening disease with a life expectancy less than 1 year 22. Atrial septostomy within 3 months preceding randomization 23. The concurrent use of the INOpulse device with a continuous positive airway pressure (CPAP), Bilevel positive airway presure BiPAP, or any other positive pressure device.

24. Use of investigational drugs or devices within 1 month prior to Screening (other than acute vasodilator testing with iNO) 25. Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study 26. Any subject who has been enrolled in any previous clinical study with inhaled NO administered through pulse delivery.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2018
Sample size
Target
Accrual to date
Final
207
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS
Recruitment hospital [1] 0 0
St Vincent's Public Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [3] 0 0
Macquarie University Hospital - Sydney
Recruitment hospital [4] 0 0
Concord Repatriation General Hospital - Sydney
Recruitment hospital [5] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [6] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 0 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2747 - Kingswood
Recruitment postcode(s) [3] 0 0
2109 - Sydney
Recruitment postcode(s) [4] 0 0
2139 - Sydney
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
7000 - Hobart
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
South Dakota
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Austria
State/province [19] 0 0
Tirol
Country [20] 0 0
Austria
State/province [20] 0 0
Wien
Country [21] 0 0
Belgium
State/province [21] 0 0
Brabant
Country [22] 0 0
Belgium
State/province [22] 0 0
Bruxelles
Country [23] 0 0
Canada
State/province [23] 0 0
Alberta
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Colombia
State/province [25] 0 0
Bogotá D.C.
Country [26] 0 0
Croatia
State/province [26] 0 0
Zagreb
Country [27] 0 0
Czechia
State/province [27] 0 0
Bohemia
Country [28] 0 0
France
State/province [28] 0 0
Normandy
Country [29] 0 0
France
State/province [29] 0 0
Rhone
Country [30] 0 0
France
State/province [30] 0 0
Montpellier
Country [31] 0 0
France
State/province [31] 0 0
Nice
Country [32] 0 0
Germany
State/province [32] 0 0
Baden-Württemberg
Country [33] 0 0
Germany
State/province [33] 0 0
Bayern
Country [34] 0 0
Germany
State/province [34] 0 0
Mecklenburg-Vorpommern
Country [35] 0 0
Germany
State/province [35] 0 0
Niedersachsen
Country [36] 0 0
Germany
State/province [36] 0 0
Sachsen
Country [37] 0 0
Germany
State/province [37] 0 0
Thüringen
Country [38] 0 0
Germany
State/province [38] 0 0
Berlin
Country [39] 0 0
Israel
State/province [39] 0 0
Ashqelon
Country [40] 0 0
Israel
State/province [40] 0 0
Beer Sheba
Country [41] 0 0
Israel
State/province [41] 0 0
Haifa
Country [42] 0 0
Israel
State/province [42] 0 0
Holon
Country [43] 0 0
Israel
State/province [43] 0 0
Jerusalem
Country [44] 0 0
Israel
State/province [44] 0 0
Kfar Saba
Country [45] 0 0
Israel
State/province [45] 0 0
Peta? Tiqwa
Country [46] 0 0
Israel
State/province [46] 0 0
Ramat Gan
Country [47] 0 0
Italy
State/province [47] 0 0
BG
Country [48] 0 0
Italy
State/province [48] 0 0
MI
Country [49] 0 0
Italy
State/province [49] 0 0
PA
Country [50] 0 0
Italy
State/province [50] 0 0
RM
Country [51] 0 0
Netherlands
State/province [51] 0 0
Amsterdam
Country [52] 0 0
Portugal
State/province [52] 0 0
Lisbon
Country [53] 0 0
Portugal
State/province [53] 0 0
Mondego
Country [54] 0 0
Serbia
State/province [54] 0 0
Belgrade
Country [55] 0 0
Serbia
State/province [55] 0 0
Nis
Country [56] 0 0
Spain
State/province [56] 0 0
A Coruña
Country [57] 0 0
Spain
State/province [57] 0 0
Canarias
Country [58] 0 0
Spain
State/province [58] 0 0
Cantabria
Country [59] 0 0
Spain
State/province [59] 0 0
Castile - La Mancha
Country [60] 0 0
Spain
State/province [60] 0 0
Madrid
Country [61] 0 0
Spain
State/province [61] 0 0
Mallorca
Country [62] 0 0
Spain
State/province [62] 0 0
Barcelona
Country [63] 0 0
Spain
State/province [63] 0 0
Valladolid
Country [64] 0 0
Ukraine
State/province [64] 0 0
Dnepropetrovsk
Country [65] 0 0
Ukraine
State/province [65] 0 0
Kharkiv
Country [66] 0 0
Ukraine
State/province [66] 0 0
Kyiv
Country [67] 0 0
Ukraine
State/province [67] 0 0
Lviv
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Newcastle
Country [69] 0 0
United Kingdom
State/province [69] 0 0
West Dunbartonshire
Country [70] 0 0
United Kingdom
State/province [70] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bellerophon Pulse Technologies
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Worldwide Clinical Trials
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ashika Ahmed, MD
Address 0 0
Bellerophon Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02725372