Prolonged-Use of Inhaled Gaseous Nitric Oxide (gNO) for Adult With Non-Tuberculous Mycobacteria Infection

NCT03473314 | Completed Phase 2

• 1 other identifier: NTM-SPU-01; H18-00512
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

An open labeled Study (NCT03331445) is demonstrating encouraging safety and efficacy results for most subjects receiving 160ppm nitric oxide gas (gNO) for treatment of non-tuberculous mycobacteria (NTM) over a 15 day treatment regimen. In one subject, who had a reduction in sputum culture concentration of Bacterium bolletii from plus 3 to plus 1 corresponding to a 2-3 log10 cfu/gm reduction during the treatment, the one-week post treatment follow-up sputum culture had increased to plus 2. It is hypothesized that a longer treatment period may be necessary to fully eradicate NTM from the sputum culture in chronic lung disease. This study will extend the period of gNO exposure for a prolonged period of time (3 months) to attempt to fully eradicate the NTM in this single subject. This study will transition from the medical clinic to supervised delivery in the patient's home environment.

Conditions

Non-Tuberculous Mycobacterial Pneumonia

Keywords

Inhaled nitric oxide; Non-tuberculous mycobacteria; Drug resistant bacteria; Antimicrobial drug resistance

Outcome Measures

Primary Outcomes (1)

• Eradication of NTM in sputum

  The primary efficacy variable for this study is eradication of recovered NTM organisms in sputum colony forming unit (CFU) g (log 10) from baseline. Eradication will be defined as two negative sputum cultures post nitric oxide gas treatment over 60 days.

  365 days

Secondary Outcomes (8)

• Mean absolute change in forced expiratory volume at one second (FEV1)% from baseline.

  365 days

• Mean change in distance walked in the six-minute walk test from baseline

  365 days

• Mean change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) scores for each domain from baseline

  365 days

• Recurrence of NTM in sputum culture post NTM eradication.

  30 and 60 days post NTM eradication

• Nitric oxide delivery effect on clinical values in home delivery

  365 days

Study Arms (1)

Nitric Oxide gas at 160ppm

EXPERIMENTAL

Nitric Oxide 160ppm for 50-80 minutes two -three times a day for 365 days

Drug: Nitric Oxide gas at 160ppm

Interventions

Nitric Oxide gas at 160ppm DRUG

Nitric oxide gas at 160 ppm inhaled three times daily for 50-80 min delivered with air as the carrier via inhalation for a maximum total of 90 days (extended 365 days twice). Total dose of 480 ppm hours per day.

Also known as: Thiolanox

Nitric Oxide gas at 160ppm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Has been previously diagnosed with NTM. \[NTM defined as positive culture(s) of at least one species of Mycobacterium avium Complex (MAC) or Mycobacterium abscessus Complex (MABSC)\]
• Has been previously treated with gNO for 15 days without complete eradication of NTM but with a decrease of at least 1-2 points on cultures.
• Male or female ≥19 years of age.
• Female not pregnant at time of study.
• Oxygen saturation on room air ≥92% at screening. (able to breathe without supplemental oxygen for 60 minutes)
• Non-smoker for at least 6 months prior to screening and agrees not to smoke during the study.
• Willing and able to comply with the treatment schedule and procedures.

You may not qualify if:

• History of frequent epistaxis (\>1 episode/month)
• History of reactive pulmonary vascular hypertension
• Methemoglobin \>3% at screening
• Liver function insufficiency aspartate aminotransferase/alanine aminotransferase (AST/ALT) \>3 of normal values)
• Hemoglobin \<10 g/dl
• Thrombocytopenia (platelet count \<100,000/mm3) at screening
• Prothrombin time international ratio (INR) \> 1.3 at screening
• On supplemental oxygen during gNO treatment (SaO2 \< 90% for 50 minutes while resting in a chair).
• For women of child bearing potential:
• positive pregnancy test at screening or
• lactating or
• unwilling to practice a medically acceptable form of contraception from screening to Day 36 (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent)
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

Sponsors & Collaborators

• University of British Columbia: lead
• Mallinckrodt: collaborator

Study Sites (1)

Gordon Leslie Diamond Health Care Centre

Vancouver, British Columbia, V5Z-1L8, Canada

Location

Study Officials

• Jeremy Road, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Open label study

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 22, 2018
• Study Start: March 9, 2018
• Primary Completion: July 11, 2020
• Study Completion: July 21, 2020
• Last Updated: July 29, 2020

Record last verified: 2020-07

Locations

CA (1)