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CompletedNCT03473314Updated Jul 29, 2020

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

A Phase 2 interventional study of Nitric Oxide gas at 160ppm in Non-Tuberculous Mycobacterial Pneumonia, sponsored by University of British Columbia. Completed at 1 site in Canada. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2020-07-29.

Sponsored by University of British Columbia · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
1
Allocation
Not applicable
Ages
19 Years and older
Sex
All
01

Study 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.

Read the detailed description

Primary Objective: Determine the efficacy of prolonged delivery of inhaled nitric oxide to treat an adult patient with pulmonary NTM Primary Endpoint: Eradication of NTM growth in sputum cultures. Efficacy will be assessed by the antimicrobial effect of inhaled NO on the density of NTM species and other microorganisms in the sputum.

  • as confirmed by measurement of semi-quantitative culture sputum growth which has been verified with serial dilution technique on Day 7, 14, 21 and every 21 days thereafter for 90 days as compared to pre-treatment baseline sputum culture.

Secondary Objective(s): Determine the safety \& efficacy of inhaled nitric oxide

Secondary Endpoint(s):

  1. Safety

    • as evaluated by the number of unanticipated adverse events during home delivery in clinical labs (hematology, coagulation, and serum chemistries); in vitals; in inspired concentration of NO, O2 and NO2 delivered to subject and; in methemoglobin and oxygen saturation levels.
  2. Efficacy

    • as determined by improvement in lung function as measured by spirometry, endurance as measured by six minute walk-test and quality of life as determined by self-reporting quality of life questionnaire (CFQ-R) on Day 7, 14, 21 and every 21 days thereafter for 90 days as compared to pre-treatment baseline data.
    • as assessed by recurrence of NTM in sputum as confirmed by measurement of semi-quantitative culture sputum growth on Day 30 and 60 post treatment.
02

Conditions studied

  • Non-Tuberculous Mycobacterial Pneumonia

Keywords

  • Inhaled nitric oxide
  • Non-tuberculous mycobacteria
  • Drug resistant bacteria
  • Antimicrobial drug resistance
03

Who can participate

Ages eligible
19 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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:

    1. positive pregnancy test at screening or
    2. lactating or
    3. 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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
1 participant (actual)

Study arms

  • Experimental
    Nitric Oxide gas at 160ppm

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

    Drug: Nitric Oxide gas at 160ppm

Interventions

  • DrugNitric Oxide gas at 160ppm

    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

05

What researchers measure

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.

    Time frame: 365 days

Secondary outcomes

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

    Clinical Measurement of Mean absolute change in FEV1% from baseline to Day 365 (within group test).

    Time frame: 365 days

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

    Clinical Measurement of Mean change in distance walked in the six-minute walk test from baseline.

    Time frame: 365 days

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

    Clinical Measurement of Mean change in CFQ-R scores for each domain from baseline. Each domain measure the magnitude of severity for each of the 8 items. Respondents score each item using a 5-point likert scale ranging from 0 (no symptom) to 4 (the highest magnitude of severity). For item 1 (difficult to breathe), item 2 (feel feverish), item 3 (tired), item 6 (mucus), and item 7 (chest tightness) the response options are: 0=No symptom, 1=a little, 2=somewhat, 3=a good deal, 4=a great deal. For item 4 (chills/sweats), item 5 (cough), and item 8 (wheezing) the response options are: 0=no symptom, 1=slightly, 2=moderately, 3=very, 4=extremely.

    Time frame: 365 days

  4. Recurrence of NTM in sputum culture post NTM eradication.

    Measurement of recovered NTM organisms in sputum colony forming unit (CFU) g (log 10) post eradication. Eradication will be defined as two negative sputum cultures post nitric oxide gas treatment over 60 days.

    Time frame: 30 and 60 days post NTM eradication

  5. Nitric oxide delivery effect on clinical values in home delivery

    Safety measured as evaluated by the number of unanticipated adverse events in clinical labs (hematology, coagulation, and serum chemistries).

    Time frame: 365 days

  6. Nitric oxide delivery effect on key physiologic vital signs in home delivery

    Safety measured as evaluated by the number of unanticipated adverse events in vitals signs (blood pressure, respiratory rate) and oxygen saturation levels during NO delivery.

    Time frame: 365 days

  7. Nitric oxide effect on delivery parameter concentrations in home delivery

    Safety measured as evaluated by the number of unanticipated adverse events with inspired concentration of nitric oxide (NO), oxygen (O2) and nitrogen dioxide (NO2) delivered to subject.

    Time frame: 365 days

  8. Nitric oxide delivery effect on systemic methemoglobin levels in home delivery

    Safety measured as evaluated by the number of unanticipated adverse events in pulseoixmetric arterial methemoglobin percent levels during nitric oxide delivery.

    Time frame: 365 days

06

Study locations

1 site
  • Gordon Leslie Diamond Health Care Centre
    Vancouver, British Columbia V5Z-1L8, Canada
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03473314
Lead sponsor
University of British Columbia
Collaborators
Mallinckrodt
Responsible party
Jeremy Road (Principal Investigator, University of British Columbia) — Principal investigator
First posted
Mar 22, 2018
Start date
Mar 9, 2018
Primary completion
Jul 11, 2020
Completion
Jul 21, 2020
Last update
Jul 29, 2020

Study contacts

Jeremy Road, MD
principal investigator · University of British Columbia

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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