Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID19 Infection

NCT04290858 | Withdrawn Phase 2 DMC

• 1 other identifier: COVID19 NOgas mild
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (COVID-19) originated in China in December 2019. At present, there are no proven interventions to prevent progression of the disease. Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on COVID-19 due to the genomic similarities between this two coronaviruses. In this study we will test whether inhaled NO therapy prevents progression in patients with mild to moderate COVID-19 disease.

Conditions

Coronavirus Infections; Pneumonia, Viral; Dyspnea

Keywords

COVID-19; Pneumonia; dyspnea; Non-invasive ventilation; Respiratory failure

Outcome Measures

Primary Outcomes (1)

• Reduction in the incidence of intubation and mechanical ventilation

  The primary outcome will be the proportion of patients with mild COVID2019 who deteriorate to a severe form of the disease requiring intubation and mechanical ventilation. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.

  28 days

Secondary Outcomes (3)

• Mortality

  28 days

• Negative conversion of COVID-19 RT-PCR from upper respiratory tract

  7 days

• Time to clinical recovery

  28 days

Study Arms (2)

Nitric Oxide inhalation

EXPERIMENTAL

Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system.

Drug: Nitric Oxide

Control

NO INTERVENTION

The control group will receive the standard of treatment without any active, placebo or sham Comparator.

Interventions

Nitric Oxide DRUG

Nitric Oxide (NO) will be delivered together with the standard of care for a period of 20-30 minutes 2 times per day for 14 consecutive days from time of enrollment. Targeted concentration will have a tidal oscillation between 100 and 300 ppm, in order to maintain an average inhaled concentration from 140 to 180 ppm. The gas will be delivered through a CPAP circuit ensuring an end-expiratory pressure between 2 and 10 cmH2O or trough a non-rebreathing mask without positive end expiratory pressure, depending on the clinical needs of the patient.

Also known as: Nitric Oxide inhalation

Nitric Oxide inhalation

Eligibility Criteria

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

You may qualify if:

• Laboratory confirmed COVID19 infection defined with a positive RT-PCR from any specimen.
• Hospital admission with at least one of the following:
• fever ≥ 36.6 °C from axillary site; or ≥ 37.2°C from oral site; or ≥ 37.6°C from tympanic or rectal site.
• Respiratory rate ≥ 24 bpm
• cough
• Spontaneous breathing with or without hypoxia of any degree. Gas exchange and ventilation maybe assisted by any continuous continuous airway pressure (CPAP), or any system of Non Invasive Ventilation (NIV), with Positive End-Expiratory Pressure (PEEP) ≤ 10 cmH2O.
• ≤ 8 days since onset of the symptoms

You may not qualify if:

• Pregnancy, or positive pregnancy test in a predose examination
• Open tracheostomy
• Therapy with high flow nasal cannula
• Clinical controindication, as deemed by the attending physician

Sponsors & Collaborators

• Xijing Hospital: lead
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator

Related Publications (5)

• Chen L, Liu P, Gao H, Sun B, Chao D, Wang F, Zhu Y, Hedenstierna G, Wang CG. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing. Clin Infect Dis. 2004 Nov 15;39(10):1531-5. doi: 10.1086/425357. Epub 2004 Oct 22.

  PMID: 15546092 BACKGROUND

• Keyaerts E, Vijgen L, Chen L, Maes P, Hedenstierna G, Van Ranst M. Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxide donor compound. Int J Infect Dis. 2004 Jul;8(4):223-6. doi: 10.1016/j.ijid.2004.04.012.

  PMID: 15234326 BACKGROUND

• Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.

  PMID: 31978945 BACKGROUND

• Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.

  PMID: 32031570 BACKGROUND

• Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available.

  PMID: 32085846 BACKGROUND

MeSH Terms

Conditions

Coronavirus Infections; Pneumonia, Viral; Dyspnea; COVID-19; Pneumonia; Respiratory Insufficiency

Interventions

Nitric Oxide

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals

Study Officials

• Lei Chong, MD, PhD

  Xijing Hospital

  PRINCIPAL INVESTIGATOR

• Lorenzo Berra, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. & Ph.D.

Study Record Dates

• First Submitted: February 27, 2020
• First Posted: March 2, 2020
• Study Start: March 1, 2020
• Primary Completion: March 1, 2021
• Study Completion: February 1, 2022
• Last Updated: March 24, 2020

Record last verified: 2020-03