Study of PAH Subjects With LTOT Use That Have Demonstrated Improved Exercise Tolerance With the Use of Inhaled Nitric

NCT03602781 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: PULSE-PAH-007
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 4

Brief Summary

Study of PAH Subjects with LTOT Use that have Demonstrated Improved Exercise Tolerance with the use of Inhaled Nitric Oxide

Conditions

Pulmonary Arterial Hypertension

Keywords

PAH; Inhaled Nitric Oxide; iNO; Long Term Oxygen Therapy; Oxygen therapy

Outcome Measures

Primary Outcomes (1)

• Time to clinical worsening during iNO withdrawal for up to 8 weeks

  A clinical worsening event is defined as: 1. Death (all-cause mortality) 2. Atrial septostomy 3. Hospitalization due to worsening of PAH 4. Need to start additional specific PAH treatment 5. Decrease of \>15% in 6 Minute Walk Distance from randomization into the study 6. Worsening of WHO Functional Class (e.g., from Class II to Class III or IV, OR Class III to Class IV)

  8 weeks

Secondary Outcomes (1)

• Difference in clinical worsening events that occur during iNO withdrawal for up to 8 weeks between those treated with iNO ≥ 10 months prior to the start of withdrawal of iNO vs. those treated < 10 months prior to initiation of withdrawal to iNO.

  8 weeks

Study Arms (2)

Cohort 1: Placebo 99.999% Nitrogen

PLACEBO COMPARATOR

Randomized Withdrawal Treatment Period Week 1-8: Placebo at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day Long Term Open Label Extension Period: iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day

Drug: Placebo; Drug: iNO

Cohort 2: iNO 75 mcg/kg IBW/hr

ACTIVE COMPARATOR

Randomized Withdrawal Treatment Period Week 1-8: iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day Long Term Open Label Extension Period: iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day

Drug: iNO

Interventions

Placebo DRUG

Placebo at a dose setting of 75 mcg/kg IBW/hr

Also known as: Placebo 99.999% Nitrogen

Cohort 1: Placebo 99.999% Nitrogen

iNO DRUG

iNO at a dose setting of 75 mcg/kg IBW/hr

Also known as: Inhaled Nitric Oxide

Cohort 1: Placebo 99.999% Nitrogen; Cohort 2: iNO 75 mcg/kg IBW/hr

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form prior to the initiation of any study mandated procedures or assessments
• Subjects must be enrolled in the PULSE PAH-004 clinical trial and must have been on LTOT and on open-label treatment with iNO 75 mcg/kg IBW/hr for at least 4 months
• Subjects must have achieved ≥ 30 meter improvement in 6MWD after 4, 8 or 12 months of open-label treatment with iNO 75 mcg/kg IBW/hr as compared to either their PULSE PAH-004 Week 2 end of Run-in OR End of Study (EOS)in PULSE-PAH-004.
• Subjects are willing and considered in the judgement of the Investigator able to use the INOpulse device continuously for up to 24 hours per day
• Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) at randomization. All female subjects must use an effective method of birth control to avoid pregnancy.

You may not qualify if:

• Subjects with episodes of worsening of PAH in the last 30 days prior to PULSE PAH-007 Baseline/Randomization
• Subjects that experience Pulmonary Rebound in PULSE-PAH-004
• Change in dose or types of PAH specific therapies in the last 30 days prior to Baseline/Randomization
• Subjects who require treatment with riociguat
• Subjects who early discontinued drug/device usage due to withdrawal of consent or an adverse event requiring termination from treatment in PULSE PAH-004
• Women who are pregnant
• The concurrent use of the INOpulse device with a continuous airway pressure (CPAP), Bilevel Positive Airway Pressure (BiPAP, or any other positive pressure device.

Sponsors & Collaborators

• Bellerophon Pulse Technologies: lead
• Worldwide Clinical Trials: collaborator

Study Sites (4)

Bluhm Cardiovascular Institute, Clinical Trials Unit

Chicago, Illinois, 60611, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Peter Lougheed Centre

Calgary, Alberta, T1Y6J4, Canada

Location

Toronto General Hospital, University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Nitrogen

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Elements; Inorganic Chemicals; Gases

Study Officials

• Ashika Ahmed, MD

  Bellerophon Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: July 27, 2018
• Study Start: August 1, 2018
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2020
• Last Updated: February 21, 2023

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); CA (2)