NCT04388683

Inhaled Nitric Oxide for Preventing Progression in COVID-19

Prevention of COVID-19 Progression Through Early Administration of Inhaled Nitric Oxide.

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Tufts Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

This is a pilot randomized-controlled (2:1) open label investigation of inhaled NO to prevent progression to more advanced disease in 42 hospitalized patients with COVID-19, at risk for worsening, based on baseline systemic oxygenation and 2 or more of the major risk factors of age \> 60 years, type II DM, hypertension, and obesity.

Detailed description

Primary Objective: • To investigate the hypothesis that inhaled NO will reduce clinical worsening of hospitalized, high-risk patients with early COVID-19 to progressive systemic de-oxygenation, intubation, or death. Secondary Objectives: • To investigate the hypothesis that the beneficial effects of inhaled NO occur coincident with a decrease in systemic inflammation in COVID-19. This is a pilot randomized-controlled (2:1) open label investigation of inhaled NO to prevent progression to more advanced disease in 42 hospitalized patients with COVID-19, at risk for worsening, based on baseline systemic oxygenation and 2 or more of the major risk factors of age \> 60 years, type II DM, hypertension, and obesity. We will perform computerized block randomization (on day zero) with a 2:1 study drug-to-control ratio to receive either open label pulsed inhaled nitric oxide, in addition to standard of care, or standard of care alone. Randomization will be stratified by being in clinical severity stage 1 or stage 2. Randomization will occur in blocks of 6 subjects: 4 iNO and 2 standard of care. Subjects will receive iNO using the INO pulse device at a dose of 125 mcg/kg IBW/hr (equivalent to approximately 20 ppm) The clinical disease severity will be assessed pre-randomization as the worse of 2 scores measured 2 hours apart. Patients eligible for randomization will be those with scores of 1 or 2 (below), and randomization will be stratified according to score (1 or 2). Study drug will begin within 1 hour of randomization. Beginning on the day following randomization ("day 1"), we will be calculate clinical score, daily, as the average of 3 assessments made within 2 hour windows. The patient will be followed, and clinical stage determined daily, through discharge, death or 28 days post-randomization. Treatment will be given for up to 2 weeks unless patient deteriorates and requires escalation to high flow or intubation or improves and is no longer deemed to need therapy. The following severity score 3 times daily, based on the level of oxygenation / ventilation support, where the treatment target is 92% \<= O2 saturation \< 96% : Scale Title:7-Point Respiratory Severity Scale Scale Range: 0-6 Higher values = worse Stage Oxygen support 0\. Not receiving O2 supplementation; AND room air O2 saturation ≥95% 1. Supplemental O2 ≤ 2 liters/min; OR room air O2 saturation ≤ 94% 2. Supplemental nasal O2 \>2 and \<= 5 liters/min 3. Supplemental nasal O2 \>5 liters/min 4. HFNC or NIV with FiO2 \> 50% 5. Intubation, ECMO, or need to intubate with "Do not intubate" order 6. Death Treatment effect will also be assessed, as a secondary endpoint, via an alternate severity scale, assigned daily from the data accrued, as above, through 14 days post-randomization or discharge. Data from this pilot study will be used to plan future a larger randomized controlled outcome trial.

Conditions

• COVID-19

Interventions

Type	Name	Description
DRUG	Nitric Oxide	Subjects will receive iNO using the INO pulse device at a dose of 125 mcg/kg IBW/hr (equivalent to approximately 20 ppm). The clinical disease severity will be assessed pre-randomization as the worse of 2 scores measured 2 hours apart. Patients eligible for randomization will be those with scores of 1 or 2 (below), and randomization will be stratified according to score (1 or 2). Study drug will begin within 1 hour of randomization. Beginning on the day following randomization ("day 1"), we will be calculate clinical score, daily, as the average of 3 measurements taken within 2 hour windows centered at 6AM, 2PM, and 10PM.

Timeline

• Start date: 2020-05-12
• Primary completion: 2020-11-23
• Completion: 2020-11-23
• First posted: 2020-05-14
• Last updated: 2022-04-19
• Results posted: 2022-04-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study