Back to resultsProlonged-Use of Inhaled Gaseous Nitric Oxide (gNO) for Adult With Non-Tuberculous Mycobacteria Infection
Primary Purpose
Non-Tuberculous Mycobacterial Pneumonia
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Nitric Oxide gas at 160ppm
Sponsored by
About this trial
This is an interventional treatment trial for Non-Tuberculous Mycobacterial Pneumonia focused on measuring Inhaled nitric oxide, Non-tuberculous mycobacteria, Drug resistant bacteria, Antimicrobial drug resistance
Eligibility 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:
- 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.
Sites / Locations
- Gordon Leslie Diamond Health Care Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Nitric Oxide gas at 160ppm
Arm Description
Nitric Oxide 160ppm for 50-80 minutes two -three times a day for 365 days
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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.
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.
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.
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).
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.
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.
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.
Full Information
NCT ID
NCT03473314
First Posted
March 14, 2018
Last Updated
July 27, 2020
Sponsor
University of British Columbia
Collaborators
Mallinckrodt
1. Study Identification
Unique Protocol Identification Number
NCT03473314
Brief Title
Prolonged-Use of Inhaled Gaseous Nitric Oxide (gNO) for Adult With Non-Tuberculous Mycobacteria Infection
Official Title
Open Label Prolonged-Use of Inhaled Gaseous Nitric Oxide (gNO) for a Single Adult With Non-Tuberculous Mycobacteria Infection
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
March 9, 2018 (Actual)
Primary Completion Date
July 11, 2020 (Actual)
Study Completion Date
July 21, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia
Collaborators
Mallinckrodt
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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):
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Tuberculous Mycobacterial Pneumonia
Keywords
Inhaled nitric oxide, Non-tuberculous mycobacteria, Drug resistant bacteria, Antimicrobial drug resistance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open label study
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nitric Oxide gas at 160ppm
Arm Type
Experimental
Arm Description
Nitric Oxide 160ppm for 50-80 minutes two -three times a day for 365 days
Intervention Type
Drug
Intervention Name(s)
Nitric Oxide gas at 160ppm
Other Intervention Name(s)
Thiolanox
Intervention Description
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.
Primary Outcome Measure Information:
Title
Eradication of NTM in sputum
Description
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 Outcome Measure Information:
Title
Mean absolute change in forced expiratory volume at one second (FEV1)% from baseline.
Description
Clinical Measurement of Mean absolute change in FEV1% from baseline to Day 365 (within group test).
Time Frame
365 days
Title
Mean change in distance walked in the six-minute walk test from baseline
Description
Clinical Measurement of Mean change in distance walked in the six-minute walk test from baseline.
Time Frame
365 days
Title
Mean change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) scores for each domain from baseline
Description
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
Title
Recurrence of NTM in sputum culture post NTM eradication.
Description
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
Title
Nitric oxide delivery effect on clinical values in home delivery
Description
Safety measured as evaluated by the number of unanticipated adverse events in clinical labs (hematology, coagulation, and serum chemistries).
Time Frame
365 days
Title
Nitric oxide delivery effect on key physiologic vital signs in home delivery
Description
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
Title
Nitric oxide effect on delivery parameter concentrations in home delivery
Description
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
Title
Nitric oxide delivery effect on systemic methemoglobin levels in home delivery
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility 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:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeremy Road, MD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Gordon Leslie Diamond Health Care Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z-1L8
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Prolonged-Use of Inhaled Gaseous Nitric Oxide (gNO) for Adult With Non-Tuberculous Mycobacteria Infection
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