Inhaled Nitric Oxide for Preventing Progression in COVID-19

NCT04388683 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY00000554
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

COVID-19

Keywords

COVID-19; Inhaled Nitric Oxide

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Average Maximum Disease Severity Assessed Through 28 Days

  The clinical disease severity was assessed pre-randomization as the worse of 2 scores measured 2 hours apart. Patients eligible for randomization were those with scores of 1 or 2 (below), and randomization was stratified according to score (1 or 2). Study drug began within 1 hour of randomization. Beginning on the day following randomization ("day 1"), we calculated clinical score, daily, as the average of 3 measurements taken within 2 hour windows centered at 6AM, 2PM, and 10PM.

  28 days

Secondary Outcomes (5)

• Days to Maximum Clinical Disease Severity Score

  28 days

• Days to Maximum Outcome Severity Score

  28 days

• Number of Participants in Each Stage at Maximum Severity

  28 days

• Length of Hospital Stay

  28 days

• Mortality

  28 days

Study Arms (2)

Intervention

EXPERIMENTAL

Will receive study drug treatment.

Drug: Nitric Oxide

Control

NO INTERVENTION

Will receive standard of care.

Interventions

Nitric Oxide DRUG

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

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-85 years.
• Admitted to the hospital (med-surg or critical care) with dyspnea
• Diagnosis of COVID-19 based on either
• positive nasal or oral pharyngeal swab by PCR, or
• highly probable clinical picture based on clinical and CXR/CT scan
• Requiring oxygen supplementation OR O2 saturation on room air of ≤ 94%
• At least 2 of the following 4 risk factors for clinical worsening:
• Age \>= 60 years
• T2DM or pre-diabetes as evidenced by either treatment with a hypoglycemic agent or any documented HgA1c \>= 5.6
• Obesity, based on BMI \>= 30 kg/m2
• 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.

You may not qualify if:

• Intubated or prior intubation (during present hospitalization) or anticipated intubation within the subsequent 2 hours.
• Receiving \> 5L/min flow nasal O2 to maintain O2sat greater than or equal to 92%
• Using high-flow nasal cannula (HFNC) or non-invasive ventilation (NIV)
• Receiving iNO, a PDE5 inhibitor, oral or intravenous nitrates, nitroprusside, prilocaine, sulfonamides, or riociguat.
• 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.
• History of group 1 pulmonary hypertension.
• Pregnancy
• Active breast feeding
• Severe chronic kidney disease, either receiving renal replacement therapy or eGFR \< 15 ml/min/m2
• Acute kidney injury (AKI), evidenced by acute doubling of serum creatinine within previous 48 hours.
• Clinically relevant spontaneous alteration of mental state
• Inability to provide written informed consent.

Sponsors & Collaborators

• Tufts Medical Center: lead
• Bellerophon: collaborator

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

MeSH Terms

Conditions

COVID-19

Interventions

Nitric Oxide

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The study was terminated early by request of the company providing the iNO Drug. Our data set is small are analysis was effected by this.

Results Point of Contact

• Title: Dr. Marvin Konstam
• Organization: Tufts Medical Center

mkonstam@tuftsmedicalcenter.org

617-636-6293

Study Officials

• Marvin Konstam, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: May 14, 2020
• Study Start: May 12, 2020
• Primary Completion: November 23, 2020
• Study Completion: November 23, 2020
• Last Updated: April 19, 2022
• Results First Posted: April 19, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)