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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03473314
Recruitment Status : Completed
First Posted : March 22, 2018
Last Update Posted : July 29, 2020
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
Jeremy Road, University of British Columbia

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.

Condition or disease Intervention/treatment Phase
Non-Tuberculous Mycobacterial Pneumonia Drug: Nitric Oxide gas at 160ppm Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Open label study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Prolonged-Use of Inhaled Gaseous Nitric Oxide (gNO) for a Single Adult With Non-Tuberculous Mycobacteria Infection
Actual Study Start Date : March 9, 2018
Actual Primary Completion Date : July 11, 2020
Actual Study Completion Date : July 21, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
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.
Other Name: Thiolanox




Primary Outcome Measures :
  1. Eradication of NTM in sputum [ Time Frame: 365 days ]
    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.


Secondary Outcome Measures :
  1. Mean absolute change in forced expiratory volume at one second (FEV1)% from baseline. [ Time Frame: 365 days ]
    Clinical Measurement of Mean absolute change in FEV1% from baseline to Day 365 (within group test).

  2. Mean change in distance walked in the six-minute walk test from baseline [ Time Frame: 365 days ]
    Clinical Measurement of Mean change in distance walked in the six-minute walk test from baseline.

  3. Mean change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) scores for each domain from baseline [ Time Frame: 365 days ]
    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.

  4. Recurrence of NTM in sputum culture post NTM eradication. [ Time Frame: 30 and 60 days 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.

  5. Nitric oxide delivery effect on clinical values in home delivery [ Time Frame: 365 days ]
    Safety measured as evaluated by the number of unanticipated adverse events in clinical labs (hematology, coagulation, and serum chemistries).

  6. Nitric oxide delivery effect on key physiologic vital signs in home delivery [ Time Frame: 365 days ]
    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.

  7. Nitric oxide effect on delivery parameter concentrations in home delivery [ Time Frame: 365 days ]
    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.

  8. Nitric oxide delivery effect on systemic methemoglobin levels in home delivery [ Time Frame: 365 days ]
    Safety measured as evaluated by the number of unanticipated adverse events in pulseoixmetric arterial methemoglobin percent levels during nitric oxide delivery.



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03473314


Locations
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Canada, British Columbia
Gordon Leslie Diamond Health Care Centre
Vancouver, British Columbia, Canada, V5Z-1L8
Sponsors and Collaborators
University of British Columbia
Mallinckrodt
Investigators
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Principal Investigator: Jeremy Road, MD University of British Columbia
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Responsible Party: Jeremy Road, Principal Investigator, University of British Columbia
ClinicalTrials.gov Identifier: NCT03473314    
Other Study ID Numbers: NTM-SPU-01; H18-00512
First Posted: March 22, 2018    Key Record Dates
Last Update Posted: July 29, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jeremy Road, University of British Columbia:
Inhaled nitric oxide
Non-tuberculous mycobacteria
Drug resistant bacteria
Antimicrobial drug resistance
Additional relevant MeSH terms:
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Mycobacterium Infections
Mycobacterium Infections, Nontuberculous
Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents