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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
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.
Gordon Leslie Diamond Health Care Centre
Vancouver, British Columbia, Canada
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
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
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
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
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
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
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
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
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
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