Inhaled Gaseous Nitric Oxide (gNO) Antimicrobial Treatment of Difficult Bacterial and Viral Lung (COVID-19) Infections

NCT03331445 | Terminated Phase 2

• 1 other identifier: NTM-CTP-01: H17-02107
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Non tuberculous mycobacteria (NTM), Burkholdria spp, Aspergillus in the lung are almost impossible to eradicate with conventional antibiotics. In addition COVID-19 has know current treatment. These patients have few options to treat their lung infection. Nitric oxide has broad bactericidal and virucidal properties. It has been shown that nitric oxide was safe to be inhaled for similar cystic fibrosis patients and reduced drug resistant bacteria in the lungs. Further, research indicates that clinical isolates of NTM, Burkholderia spp, Aspergillus spp and Corona-like viruses can be eradicated by 160ppm NO exposure in the laboratory petri dish. This is not the first time inhaled NO treatment has been used in patients with difficult lung infections. This study will provide more data to see if NO therapy can reduce the bacterial load in the lungs, help the patients breath better; and in the case of COVID-19 act as a anti-viral agent resulting in the reduction of incidence of oxygen therapy, mechanical assistance of BIPAP, CPAP, intubation and mechanical ventilation during the study period.

Conditions

Respiratory Tract Infections; Corona Virus Infection

Keywords

inhaled nitric oxide; non tuberculous mycobacteria; drug resistant pneumonia; Burkholderia; Aspergillus; COVID-19; Viral Envelope Proteins; SARS-COV-2

Outcome Measures

Primary Outcomes (1)

• Measure the safety of 160ppm inhaled nitric oxide delivery in NTM subjects

  Measure the number of unanticipated adverse events over the duration of the study protocol

  26 Days

Secondary Outcomes (3)

• Measure the effect of 160ppm inhaled nitric oxide delivery on lung spirometry in NTM subjects

  Day 5,12,19 and 26

• Measure the antimicrobial effect of 160ppm inhaled nitric oxide on lung NTM bacterial load in the sputum

  Day 19 and 26

• Measure the effect of 160ppm inhaled nitric oxide on Quality of Life (CRISS) Score

  Day 19 and 26

Other Outcomes (5)

• Sub-Study Primary Endpoint(s): Efficacy to reduce respiratory interventions

  Day 26

• Efficacy in reduction of mortality

  Day 26

• Antiviral effect

  Day 26

Study Arms (1)

160 ppm Nitric Oxide

EXPERIMENTAL

Drug: Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation

Interventions

Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation DRUG

Inhaled Nitric Oxide 160ppm balance air

Also known as: Thiolanox

160 ppm Nitric Oxide

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
• Men and Women ≥ 19 years of age unless local laws dictate otherwise;
• English speaking;
• Suspected of exposure to SARS-CoV-2 with fatigue and at least a fever (\>37.90 C) or cough or sore throat or a positive swab for SAR-CoV-2 within 5 days of the of enrollment;
• Must be willing to use an adequate form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP.

You may not qualify if:

• Prior Tracheostomy;
• Concomitant treatment involving high flow nasal cannula;
• Any clinical contraindications, as judged by the attending physician;
• Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
• Prior COVID-19 infection or a positive swab for SARS-CoV-2 greater than 5 days from enrollment;
• Family members in the same household already on the study;
• Hydroxychloroquine, colchicine and other experimental antiviral medications;
• unwilling to practice a medically acceptable form of contraception from screening to Day 26 (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent).
• Recruitment on hold for following Criteria during COVID-19 Pandemic
• Written informed consent.
• Has been previously diagnosed with NTM, Burkholderia spp and Aspergillus spp. or Corona-like viral infection:
• 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:
• 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.

Sponsors & Collaborators

• Chris Miller: lead
• Mallinckrodt: collaborator

Study Sites (1)

Nitric Solutions-Mobile Unit

Vancouver, British Columbia, V7H2Y4, Canada

Location

Related Publications (3)

• Deppisch C, Herrmann G, Graepler-Mainka U, Wirtz H, Heyder S, Engel C, Marschal M, Miller CC, Riethmuller J. Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study. Infection. 2016 Aug;44(4):513-20. doi: 10.1007/s15010-016-0879-x. Epub 2016 Feb 9.

  PMID: 26861246 BACKGROUND

• Miller C, Miller M, McMullin B, Regev G, Serghides L, Kain K, Road J, Av-Gay Y. A phase I clinical study of inhaled nitric oxide in healthy adults. J Cyst Fibros. 2012 Jul;11(4):324-31. doi: 10.1016/j.jcf.2012.01.003. Epub 2012 Apr 18.

  PMID: 22520076 BACKGROUND

• Yaacoby-Bianu K, Gur M, Toukan Y, Nir V, Hakim F, Geffen Y, Bentur L. Compassionate Nitric Oxide Adjuvant Treatment of Persistent Mycobacterium Infection in Cystic Fibrosis Patients. Pediatr Infect Dis J. 2018 Apr;37(4):336-338. doi: 10.1097/INF.0000000000001780.

  PMID: 28885458 BACKGROUND

MeSH Terms

Conditions

Respiratory Tract Infections; Coronavirus Infections; COVID-19

Interventions

Nitric Oxide; Nitrogen; Gases; Inhalation

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals; Elements; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Jeremy D Road, MD

  MD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: CSO

Model Details: Open label safety study (COVID-19 Sub-study)

Study Record Dates

• First Submitted: October 25, 2017
• First Posted: November 6, 2017
• Study Start: October 24, 2017
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: July 16, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)