Clinical trial NCT04358588: Pulsed Inhaled Nitric Oxide for the Treatment of Patients With Mild or Moderate COVID-19
Official title: Expanded Access: Pulsed, Inhaled Nitric Oxide (iNO) for the Treatment of Patients With Mild or Moderate Coronavirus Disease (COVID-19)
Study type: EXPANDED_ACCESS
Overall status: NO_LONGER_AVAILABLE
Conditions: Coronavirus Infection
COVID-19
Pneumonia, Viral
Keywords: coronavirus
corona virus
COVID-19
COVID 19
SARS
SARS-coronavirus
Pneumonia
Pneumonia, viral
Virus
Lead sponsor: Bellerophon
Sponsor class: INDUSTRY
First posted: 2020-04-24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT

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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Bellerophon Therapeutics
name: Ashika Ahmed, MD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1016/j.ijid.2004.04.012.
citation: Akerstrom S, Mousavi-Jazi M, Klingstrom 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. doi: 10.1128/JVI.79.3.1966-1969.2005.
citation: 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. doi: 10.1086/425357. Epub 2004 Oct 22.