Pulsed Inhaled Nitric Oxide for the Treatment of Patients With Mild or Moderate COVID-19

• ClinicalTrials.gov Identifier: NCT04358588
• Expanded Access Status: No longer available
• First Posted: April 24, 2020
• Last Update Posted: June 12, 2020
• Sponsor: Bellerophon
• Information provided by (Responsible Party): Bellerophon

Study Description

Brief Summary:

The search for novel therapies to address the ongoing coronavirus (COVID-19) pandemic is ongoing. No proven therapies have been identified to prevent progression of the virus. Preliminary data suggest that inhaled nitric oxide (iNO) could have benefit in preventing viral progression and reducing reliance on supplemental oxygen and ventilator support.

Expanded access allows for iNO to be delivered via the portable INOpulse delivery system for the treatment of COVID-19.

Condition or disease	Intervention/treatment
Coronavirus Infection; COVID-19; Pneumonia, Viral	Drug: iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System

Detailed Description:

NO is a naturally produced molecule that is critical to the immune response to defend against pathogens and infections. In vitro studies have shown that NO inhibits the replication of severe acute respiratory syndrome-related coronavirus (SARS-CoV) and improves survival for cells infected with SARS-CoV. Additionally, in a clinical study of patients infected with SARS-CoV, iNO demonstrated improvements in arterial oxygenation, a reduction in ventilation support and an improvement in lung infiltrates observed on chest radiography. Based on the genetic similarities between the two coronaviruses, the data in SARS-CoV support the potential for iNO to provide meaningful benefit for patients infected with COVID-19.

The clinical spectrum of the COVID-19 infection ranges from mild signs of upper respiratory tract infection to severe pneumonia and death. Preventing disease progression in patients with mild or moderate disease would improve morbidity/mortality and significantly reduce the impact on limited healthcare resources.

Expanded access allows for iNO to be delivered via the INOpulse delivery system for the treatment of COVID-19. INOpulse technology provides targeted pulsatile delivery of iNO via portable INOpulse delivery system.

Study Design

• Study Type: Expanded Access
• Expanded Access Type: Intermediate-size Population
• Official Title: Expanded Access: Pulsed, Inhaled Nitric Oxide (iNO) for the Treatment of Patients With Mild or Moderate Coronavirus Disease (COVID-19)

Interventions

Intervention Details:

• Drug: iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System
  Patients will be treated by means of an INOpulse device and cannula. The active study drug, nitric oxide for inhalation (iNO), will be provided in size 0.074 liter aluminum cartridge at a concentration of 6.0 mg/L (4880 ppm).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 95 Years (Adult, Older Adult)
• Sexes Eligible for Study: All

Criteria

Inclusion Criteria:

1. Signed Informed Consent Form (and assent as appropriate) prior to the initiation of any study mandated procedures or assessments.
2. At least 18 years old
3. Patients with proven or high suspicion of SARS-CoV-2 infection and on supplemental oxygen ≤ 10 L/minute
4. Suspected or proven pneumonia on chest imaging
5. Female patients of childbearing potential must have a negative pre-treatment pregnancy test (serum or urine). All female patients should take adequate precaution to avoid pregnancy.
6. Willing and able to comply with treatment schedule and study procedures.

Exclusion Criteria:

1. Participating in any other clinical trial of an experimental treatment for COVID-19
2. Gas exchange and ventilation requiring the use of any continuous positive airway pressure (CPAP), or any system of Non Invasive Ventilation (NIV), with Positive End-Expiratory Pressure (PEEP) ≤ 10 cmH2O prior to initiation of iNO
3. Pregnancy, or positive pregnancy test in a pre-dose examination
4. Open tracheostomy
5. Clinical contra-indication, as deemed by the attending physician
6. Use of a nitric oxide donor agent such as nitroglycerin or drugs known to increase methemoglobin such as lidocaine, prilocaine, benzocaine or dapsone at screening
7. Known history or clinical evidence of heart failure, left ventricular dysfunction (LVEF < 40 %)
8. Patients reporting hemoptysis

Contacts and Locations

Sponsors and Collaborators

Bellerophon

Investigators

• Study Director: Hunter Gilles, MD; Acting Chief Medical Officer

More Information

Publications:

Keyaerts E, Vijgen L, Chen L, Maes P, Hedenstierna G, Van Ranst M. Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxide donor compound. Int J Infect Dis. 2004 Jul;8(4):223-6.

Akerström S, Mousavi-Jazi M, Klingström J, Leijon M, Lundkvist A, Mirazimi A. Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J Virol. 2005 Feb;79(3):1966-9.

Chen L, Liu P, Gao H, Sun B, Chao D, Wang F, Zhu Y, Hedenstierna G, Wang CG. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing. Clin Infect Dis. 2004 Nov 15;39(10):1531-5. Epub 2004 Oct 22.

• Responsible Party: Bellerophon
• ClinicalTrials.gov Identifier: NCT04358588
• Other Study ID Numbers: PULSE-EAP-001
• First Posted: April 24, 2020
• Last Update Posted: June 12, 2020
• Last Verified: June 2020

Keywords provided by Bellerophon:

coronavirus; corona virus; COVID-19; COVID 19; SARS; SARS-coronavirus; Pneumonia; Pneumonia, viral; Virus

Additional relevant MeSH terms:

Coronavirus Infections; Pneumonia, Viral; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Nitric Oxide; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Endothelium-Dependent Relaxing Factors; Vasodilator Agents; Gasotransmitters; Protective Agents