Nitric Oxide for COVID-19

(NoCovid Trial)

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Disqualifiers: Tracheostomy, High flow nasal cannula, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether inhaling Nitric Oxide can halt the progression of COVID-19 in patients with mild to moderate symptoms. Nitric Oxide has shown promise in earlier studies on similar viruses, and researchers aim to determine its effectiveness against COVID-19. The trial divides participants into groups: one receives the Nitric Oxide treatment, while the other does not, to compare outcomes. People with COVID-19 who have a fever, cough, or trouble breathing might be suitable candidates if hospitalized for less than 72 hours. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that inhaled Nitric Oxide is likely to be safe for humans?

Research has shown that inhaled nitric oxide (iNO) is generally safe for treating patients, including those with COVID-19. Studies have found that patients tolerate iNO well, even at high doses. For instance, one study found that using high doses of iNO occasionally was safe for adults with COVID-19. Another study reported that a single high dose of iNO did not cause significant side effects when used in the emergency room. Additionally, iNO has been associated with improving oxygen levels in patients with severe breathing problems, although it did not lower death rates. This evidence suggests that inhaled nitric oxide is relatively safe for use in humans, even in challenging health situations like COVID-19. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about nitric oxide for COVID-19 because it offers a unique approach compared to standard treatments like antivirals, steroids, and monoclonal antibodies. Nitric oxide works by directly targeting the respiratory system, where COVID-19 often causes severe issues, and is delivered through inhalation, which might provide rapid relief. This method could reduce respiratory distress more quickly than systemic treatments because it acts right at the site of infection. Additionally, as a gas administered via CPAP or a non-rebreathing mask, it minimizes the discomfort often associated with invasive ventilation methods.

What evidence suggests that inhaled Nitric Oxide could be an effective treatment for COVID-19?

Research suggests that inhaled nitric oxide (iNO) might help people with COVID-19. This trial includes a treatment arm where participants receive nitric oxide inhalation, known to improve oxygen levels in patients with severe lung distress. Some studies have shown that iNO can slightly improve lung function within 48 hours. Nitric oxide also reduces inflammation and fights germs, which might help combat the virus. While more research is needed specifically for COVID-19, early results are promising based on its use in similar conditions. ^{2 6 7 8 9}

Who Is on the Research Team?

Lorenzo Berra, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for people with confirmed COVID-19 showing mild to moderate symptoms like fever, cough, or breathing difficulties but not severe enough to require high-flow oxygen or intubation. They must be newly hospitalized and not part of another study. Those with tracheostomies, on certain oxygen therapies, or with other health issues that the doctor thinks could interfere are excluded.

Inclusion Criteria

You have tested positive for COVID-19 through a lab test or have antibodies for the virus.

I was admitted to the hospital with a fever measured from underarm, mouth, ear, or rectum.

I can breathe on my own, even if I need some assistance.

Exclusion Criteria

I was hospitalized for reasons other than COVID-19.

I am currently using a high flow nasal cannula for breathing support.

I have been in the hospital with COVID-19 for over 72 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive inhaled Nitric Oxide therapy to prevent progression of mild to moderate COVID-19

3 days

Daily visits (inpatient or outpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

What Are the Treatments Tested in This Trial?

Interventions

• Nitric Oxide

Trial Overview The trial is testing if inhaling Nitric Oxide (NO) gas can stop the worsening of COVID-19 in patients. NO has shown promise against similar viruses in the past. Participants will breathe in NO through a mask or tube to see if it helps improve their lung function and prevents severe disease progression.

How Is the Trial Designed?

Group I: Nitric Oxide inhalation Experimental Treatment 1 Intervention

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.

Group II: Nitric Oxide Inhalation (Non-Randomized) Experimental Treatment 1 Intervention

All subjects part of this arm will receive nitric oxide gas either as an inpatient or outpatient. 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. Patients in this arm will not be randomized, so that all patients receive the study medication.

Group III: Control Active Control 1 Intervention

Patients assigned to the control group will not receive any gas therapy.

Nitric Oxide is already approved in United States for the following indications:

Approved in United States as Inomax for:

• Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension

Approved in United States as Noxivent for:

• Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension

Approved in United States as GeNOsyl for:

• Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

Citations

1. mallinckrodt.gcs-web.com mallinckrodt.gcs-web.com/news-releases/news-release-details/mallinckrodt-supports-investigator-initiated-study-massachusetts

Release Details - Investor Relations "Data suggest that inhaled nitric oxide may have an important role in helping patients with acute respiratory distress syndrome (ARDS) to achieve normal oxygen ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9007062/

Real-world use of inhaled nitric oxide therapy in patients with ... Effectiveness outcomes. The mean P/F ratio (SD) increased from 136.7 (34.4) at baseline to 140.3 (53.2) at 48 hours after iNO initiation (n=34) (Figure 2) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04305457

Nitric Oxide Gas Inhalation Therapy for Mild/Moderate ... Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on SARS-CoV-2 due to the genomic similarities ...

4. nature.com nature.com/articles/s41598-024-68055-w

A safety evaluation of intermittent high-dose inhaled nitric ... High-dose inhaled Nitric Oxide (iNO) has been shown to have anti-inflammatory, vasodilator, and antimicrobial properties, resulting in ...

5. respiratory-therapy.com respiratory-therapy.com/disorders-diseases/critical-care/ards/inhaled-nitric-oxide-covid-19-ards/

Study Evaluates Inhaled Nitric Oxide for COVID-19 | RT Researchers assessed outcomes of INOmax inhaled nitric oxide for COVID-19 patients hospitalized with mild-to-moderate ARDS.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12378598/

Inhaled nitric oxide for the treatment of COVID-19 The aim of this study was to evaluate safety and efficacy of iNO 160 ppm on supplemental oxygen in patients hospitalised with COVID-19. Methods.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04476992

Nitric Oxide Therapy for COVID-19 Patients With Oxygen ... Preliminary data support the effect of Nitric Oxide (NO) on improving the oxygenation in mechanically ventilated patients and spontaneously breathing ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8262415/

Efficacy and safety of inhaled nitric oxide in the treatment ... In patients with COVID-19 with acute respiratory distress syndrome, nitric oxide is linked to a slight increase in oxygenation but has no effect on mortality.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0735675722002832

Safety and practicality of high dose inhaled nitric oxide in ... A single dose of iNO at 250 ppm was practical and not associated with any significant adverse effects when administered in the ED by emergency physicians.