Inhaled Nitric Oxide for Preventing Progression in COVID-19
Condition: COVID-19
MeSH terms: COVID-19
Intervention: Nitric Oxide
Intervention description: 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.
Intervention MeSH terms: Nitric Oxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: COVID-19; Inhaled Nitric Oxide

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18-85 years.

          2. Admitted to the hospital (med-surg or critical care) with dyspnea

          3. Diagnosis of COVID-19 based on either

               1. positive nasal or oral pharyngeal swab by PCR, or

               2. highly probable clinical picture based on clinical and CXR/CT scan

          4. Requiring oxygen supplementation OR O2 saturation on room air of ≤ 94%

          5. At least 2 of the following 4 risk factors for clinical worsening:

               1. Age >= 60 years

               2. T2DM or pre-diabetes as evidenced by either treatment with a hypoglycemic agent
                  or any documented HgA1c >= 5.6

               3. Obesity, based on BMI >= 30 kg/m2

               4. Hypertension, based on treatment with an antihypertensive medication or systolic
                  or diastolic blood pressure measurement >= 140 or >= 90 mmHg, documented at
                  enrollment or at any time within the prior 6 months.

        Exclusion Criteria:

          1. Intubated or prior intubation (during present hospitalization) or anticipated
             intubation within the subsequent 2 hours.

          2. Receiving > 5L/min flow nasal O2 to maintain O2sat greater than or equal to 92%

          3. Using high-flow nasal cannula (HFNC) or non-invasive ventilation (NIV)

          4. Receiving iNO, a PDE5 inhibitor, oral or intravenous nitrates, nitroprusside,
             prilocaine, sulfonamides, or riociguat.

          5. Other major pulmonary, cardiac, such as chronic obstructive lung disease or heart
             failure, or systemic illness or disease involvement with potential to represent the
             primary driver for clinical deterioration within the next 3 days.

          6. History of group 1 pulmonary hypertension.

          7. Pregnancy

          8. Active breast feeding

          9. Severe chronic kidney disease, either receiving renal replacement therapy or eGFR < 15
             ml/min/m2

         10. Acute kidney injury (AKI), evidenced by acute doubling of serum creatinine within
             previous 48 hours.

         11. Clinically relevant spontaneous alteration of mental state

         12. Inability to provide written informed consent.