Nitric Oxide Therapy for COVID-19 Patients With Oxygen Requirement

NCT04476992 | Completed Phase 1

• 1 other identifier: NICOR
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Preliminary data support the effect of Nitric Oxide (NO) on improving the oxygenation in mechanically ventilated patients and spontaneously breathing patients with COVID-19. In vitro studies showed an antiviral effect of NO against SARS-coronavirus. The optimal therapeutic regimen of NO gas in spontaneously breathing hypoxemic patients with COVID-19 is not known. We hypothesize that high concentration inhaled NO with an adjunct of continuous low dose administration between the high concentration treatments can be safely administered in hypoxemic COVID-19 patients compared to the high dose treatment alone. Prolonged administration of NO gas may benefit the patients in terms of the severity of the clinical course and time to recovery. Together with a clinical effect on ventilation-perfusion matching, a prolonged regimen would allow also an increase in antiviral activity (dose and time-dependent).

Conditions

Hypoxemia; Pneumonia, Viral; Coronavirus Infection

Keywords

Nitric Oxide gas; COVID-19; Hypoxemia; Viral Pneumonia

Outcome Measures

Primary Outcomes (1)

• Change in Methemoglobin level at 48 hours

  The primary outcome will be evaluated with the difference in Methemoglobin levels between the groups at 48 hours after randomization.

  48 hours

Secondary Outcomes (8)

• Change in Methemoglobin level at 96 hours

  96 hours

• Improvement in oxygenation between the groups at 48 hours or at discharge if before 48 hours

  48 hours

• Improvement in oxygenation between the groups at 96 hours or at discharge if before 96 hours

  96 hours

• Rate of positive RT-PCR for SARS-CoV-2 between groups in 5 days, discharge, and 28 days

  28 days

• Time to clinical recovery among groups, defined as time to interruption of oxygen administration for 24 hours or discharge

  28 days

Other Outcomes (2)

• Effect of NO gas treatment on cardiovascular hemodynamics assessed using cardiac ultrasound in COVID-19 hypoxemic patients

  96 hours

• Effect of NO gas treatment on lung function evaluated with serial spirometry in COVID-19 hypoxemic patients

  96 hours

Study Arms (2)

NO High Concentration

ACTIVE COMPARATOR

Nitric oxide will be delivered twice a day with a non-rebreathing system that allows a safe administration of Nitric Oxide gas at high concentrations limiting the amount of NO2 delivered to the patient.

Drug: Nitric Oxide-Sessions

NO High Concentration + Continuous Low Concentration

EXPERIMENTAL

Nitric oxide will be delivered twice a day with a non-rebreathing system that allows a safe administration of Nitric Oxide gas at high concentrations limiting the amount of NO2 delivered to the patient. This arm will receive in addition a continuous low flow of Nitric Oxide at 20 ppm among the high concentration treatments.

Drug: Nitric Oxide-Continuous and Sessions

Interventions

Nitric Oxide-Sessions DRUG

Nitric Oxide will be delivered at 200 ppm in 2 daily sessions (morning, evening; 9-12 hours apart) for 14 days. Each session will last 30 minutes, for a total of 60 minutes/day for each patient. A tank of NO gas will be connected to the inspiratory limb of the circuit, and the flow will be adjusted to deliver a target concentration of 200 ppm NO. Commercially available tanks will be used to provide the gas. The desired mixture of air, oxygen (O2), and NO will be titrated with the respective flowmeter to reach a concentration of 200 ppm at the inspiratory limb with the desired Fraction of inspired oxygen (FiO2).

Also known as: Nitric Oxide inhalation at high concentration

NO High Concentration

Nitric Oxide-Continuous and Sessions DRUG

Nitric Oxide will be delivered at 200 ppm in 2 daily sessions (morning, evening; 9-12 hours apart) for 14 days. Each session will last 30 minutes, for a total of 60 minutes/day for each patient. A tank of NO gas will be connected to the inspiratory limb of the circuit, and the flow will be adjusted to deliver a target concentration of 200 ppm NO. Commercially available tanks will be used to provide the gas. The desired mixture of air, oxygen (O2), and NO will be titrated with the respective flowmeter to reach a concentration of 200 ppm at the inspiratory limb with the desired Fraction of inspired oxygen (FiO2). The subjects assigned to the group "NO High Concentration + Continuous Low Concentration" will receive in adjunction a continuous dose of NO at 20 ppm.

Also known as: Nitric Oxide inhalation at high concentration + low concentration

NO High Concentration + Continuous Low Concentration

Eligibility Criteria

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

You may qualify if:

• COVID-19 confirmed by a positive RT-PCR test
• Hospital admission within 11 days from the onset of symptoms
• Spontaneous breathing with oxygen requirement ≥1 L/min
• Expected discharge \> 96 hours at randomization

You may not qualify if:

• Pregnancy
• Presence of a tracheostomy
• Assistance by any non-invasive CPAP or NIV at the screening
• Treatment with high flow nasal cannula at the screening
• Clinical contraindication to the use of NO
• Patients enrolled in another interventional trial
• Hospitalized and confirmed diagnosis of COVID-19 for more than 7 days
• Previous intubation for COVID-19
• Subject not committed to full support (DNR, DNI or CMO)
• Subject requiring oxygen at home for lung comorbidities
• The primary cause of hospitalization not due to COVID-19
• Subject receiving vasopressor at the time of screening
• History of malignancy or other irreversible disease/conditions with 6-month mortality \>50%
• Oxygen saturation of 100% at screening, despite oxygen requirement
• Patients on dialysis at the time of enrollment

Sponsors & Collaborators

• Tomsk National Research Medical Center of the Russian Academy of Sciences: lead
• Siberian State Medical University: collaborator

Study Sites (1)

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Tomsk, 634012, Russia

Location

Related Publications (1)

• Kamenshchikov NO, Safaee Fakhr B, Kravchenko IV, Dish AY, Podoksenov YK, Kozlov BN, Kalashnikova TP, Tyo MA, Anfinogenova ND, Boshchenko AA, Berra L. Assessment of continuous low-dose and high-dose burst of inhaled nitric oxide in spontaneously breathing COVID-19 patients: A randomized controlled trial. Nitric Oxide. 2024 Aug 1;149:41-48. doi: 10.1016/j.niox.2024.06.003. Epub 2024 Jun 14.

  PMID: 38880198 DERIVED

MeSH Terms

Conditions

Hypoxia; Pneumonia, Viral; Coronavirus Infections; COVID-19

Condition Hierarchy (Ancestors)

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

Study Officials

• Nikolay O Kamenshchikov, M.D.

  Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 20, 2020
• Study Start: July 24, 2020
• Primary Completion: July 17, 2021
• Study Completion: September 17, 2021
• Last Updated: January 26, 2023

Record last verified: 2022-04

Locations

RU (1)