Inhaled Gaseous Nitric Oxide (gNO) Antimicrobial Treatment of Difficult Bacterial and Viral Lung (COVID-19) Infections
Ключови думи
Резюме
Описание
Main Study
Primary Objective: Assess the safety of inhaled NO (gNO) in adults & adolescents with NTM, Burkholderia and Aspergillus Lung Infections
Safety will be evaluated by unanticipated adverse events in clinical labs (hematology, coagulation, and serum chemistries); in vitals; in inspired concentration of NO, O2 and NO2 delivered to each subject and; in real time methemoglobin and oxygen saturation levels.
Primary Endpoint:
Determine the safety of gNO in the NTM population,
- as confirmed by no unanticipated adverse events
- Absence of a deleterious mean change in FEV1% predicted (absolute) from baseline
Secondary safety Endpoint: Determine the efficacy of inhaled NO in adults with NTM, Burkholderia and Aspergillus Lung Infections
Efficacy will be evaluated by measuring the change in lung function with spirometry (specifically absolute change in FEV1 % predicted) from baseline to Days 5, 12, 19 and 26.
Secondary Efficacy Endpoint Determine the presence of an efficacy signal of gNO in the NTM, Burkholderia and Aspergillus Lung Infections
Efficacy will be assessed by the antimicrobial effect of inhaled NO on the density of NTM species and other microorganisms in sputum. Serial measurements of these microbial colony counts in sputum have been previously used as a measure of antimicrobial activity in other clinical trials of antibiotics in NTM.
• as confirmed by an improvement in pre-treatment bacterial colonization and post-treatment bacterial colonization on Days 19 and 26 as compared to baseline.
Efficacy will be assessed by change in Quality of Life Score.
- as assessed by an improvement in CRISS Score on Day 5, 19 and 26 as compared to baseline measurement;
- as determined by improvement in six-minute walk test with one minute recovery as compared to baseline measurement.
COVID-19 Substudy
Primary Endpoint:
Efficacy will be evaluated by measuring reduction in the incidence of mechanical assistance of BIPAP, CPAP, intubation and mechanical ventilation during the study period.
Secondary Endpoints:
1. Proportion of patients with mild COVID2019 who deteriorate to a severe form of the disease requiring mechanical intervention like BIPAP/CPAP, intubation and mechanical ventilation;
2. Mortality from all causes during the study period;
3. Negative conversion of COVID-19 RT-PCR from upper respiratory tract measured as the proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or a nasopahryngeal swab;
4. Time to clinical recovery defined as the time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air);
5. Alleviation of symptoms recorded in the Modified Jackson Cols score with particular definition of cough (defined as mild or absent in a patient reported scale of severity).
Дати
| Последна проверка: | 02/29/2020 |
| Първо изпратено: | 10/24/2017 |
| Очаквано записване подадено: | 10/30/2017 |
| Първо публикувано: | 11/05/2017 |
| Изпратена последна актуализация: | 03/27/2020 |
| Последна актуализация публикувана: | 03/30/2020 |
| Действителна начална дата на проучването: | 10/23/2017 |
| Приблизителна дата на първично завършване: | 12/30/2020 |
| Очаквана дата на завършване на проучването: | 03/30/2021 |
Състояние или заболяване
Интервенция / лечение
Drug: 160 ppm Nitric Oxide
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| Experimental: 160 ppm Nitric Oxide | Drug: 160 ppm Nitric Oxide Inhaled Nitric Oxide 160ppm balance air |
Критерии за допустимост
| Възрасти, отговарящи на условията за проучване | 14 Years Да се 14 Years |
| Полове, допустими за проучване | All |
| Приема здрави доброволци | Да |
| Критерии | Inclusion Criteria: - Written informed consent. - Has been previously diagnosed with NTM, Burkholderia spp and Aspergillus spp. or Corona-like viral infection: 1. NTM, Burkholderia spp and Aspergillus spp defined as positive culture(s) of at least one species of Mycobacterium avium Complex (MAC) or Mycobacterium abscessus Complex (MABSCor Burkholderia spp and Aspergillus spp) or Corona-like viral infection: 2. History of repeatedly positive cultures (2 or more), irregardless of therapy - Male or female ≥14 years of age. - Female not pregnant at time of study. - Has an FEV1 ≥ 30 % of predicted. c. Suspected corona-like viral infection - Oxygen saturation on room air >92% at screening. a. 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: - Use of an investigational drug within 30 days of screening - History of frequent epistaxis (>1 episode/month) - Significant hemoptysis within 30 days (≥ 5 mL of blood in one coughing episode or > 30 mL of blood in a 24 hour period) - History of reactive pulmonary vascular hypertension - Methemoglobin >3% at screening - Liver function insufficiency (ALT/ AST >3 of normal values) - Hemoglobin <11 g/dl - Thrombocytopenia (platelet count <100,000/mm3) at screening - Prothrombin time international ratio (INR) > 1.3 at screening - Changes to antibiotics (e.g. azithromycin) from 7 days prior to screening through last treatment day. (Subjects may be taking antibiotics or antivirals during this time period, but they cannot start, stop or change doses during this time period) - 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. |
Резултат
Първични изходни мерки
1. Measure the safety of 160ppm inhaled nitric oxide delivery in NTM subjects [26 Days]
Вторични изходни мерки
1. Measure the effect of 160ppm inhaled nitric oxide delivery on lung spirometry in NTM subjects [Day 5,12,19 and 26]
2. Measure the antimicrobial effect of 160ppm inhaled nitric oxide on lung NTM bacterial load in the sputum [Day 19 and 26]
3. Measure the effect of 160ppm inhaled nitric oxide on Quality of Life (CRISS) Score [Day 19 and 26]
Други изходни мерки
1. Sub-Study Primary Endpoint(s): Efficacy to reduce respiratory interventions [Day 26]
2. Efficacy in reduction of mortality [Day 26]
3. Antiviral effect [Day 26]
4. Efficacy on clinical improvement [Day 26]
5. Efficacy on the respiratory symptoms [Day 26]
