Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19 (NoCovid)
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|ClinicalTrials.gov Identifier: NCT04305457|
Recruitment Status : Recruiting
First Posted : March 12, 2020
Last Update Posted : April 3, 2020
|Condition or disease||Intervention/treatment||Phase|
|Coronavirus Infections Pneumonia, Viral Acute Respiratory Distress Syndrome||Drug: Nitric Oxide||Phase 2|
To date, no targeted therapeutic treatments for the ongoing COVID-19 outbreak have been identified. Antiviral combined with adjuvant therapies are currently under investigation. The clinical spectrum of the infection is wide, ranging from mild signs of upper respiratory tract infection to severe pneumonia and death.
In the patients who progress, the time period from symptoms onset to development of dyspnea is reported to be between 5 to 10 days, and that one to severe respiratory distress syndrome from 10 to 14 days. Globally, 15 to 18% of patients deteriorates to the need of mechanical ventilation, despite the use of non-invasive ventilatory support in the earliest phases of the disease. Probability of progression to end stage disease is unpredictable, with the majority of these patients dying from multi-organ failure. Preventing progression in spontaneously breathing patients with mild to moderate disease would translate in improved morbidity and mortality and in a lower use of limited healthcare resources.
In 2004, during the SARS-coronavirus (SARS-CoV) outbreak, a pilot study showed that low dose ( max 30 ppm) inhaled NO for 3 days was able to shorten the time of ventilatory support. At the same time, NO donor compound S-nitroso-N-acetylpenicillamine increased survival rate in an in-vitro model of SARS-CoV infected epithelial cells.Based on the genetic similarities between the two viruses, similar effects of NO on SARS-CoV-2 can be hypothesized. While further in-vitro testing is recommended, we proposed a randomized clinical trial to test the effectiveness of inhaled NO in preventing the progression of SARS-CoV-2 related disease, when administered at an early stage.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||240 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Nitric Oxide Gas Inhalation Therapy in Spontaneous Breathing Patients With Mild/Moderate COVID-19: a Randomized Clinical Trial|
|Actual Study Start Date :||March 21, 2020|
|Estimated Primary Completion Date :||April 1, 2021|
|Estimated Study Completion Date :||April 1, 2022|
Experimental: Nitric Oxide inhalation
Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system.
Drug: Nitric Oxide
Nitric Oxide (NO) will be delivered together with the standard of care for a period of 20-30 minutes 2 times per day for 14 consecutive days from time of enrollment. Targeted No inhaled concentration will be maintained between 140 and 180 ppm. The gas will be delivered through a CPAP circuit ensuring an end-expiratory pressure between 2 and 10 cmH2O or through a non-rebreathing mask without positive end-expiratory pressure, depending on the clinical needs of the patient.
Other Name: Nitric Oxide inhalation
No Intervention: Control
Patients assigned to the control group will not receive any gas therapy.
- Reduction in the incidence of patients with mild/moderate COVID-19 requiring intubation and mechanical ventilation [ Time Frame: 28 days ]The primary outcome will be the reduction in the incidence of patients requiring intubation and mechanical ventilation, as a marker of deterioration from a mild to a severe form of COVID-19. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.
- Mortality [ Time Frame: 28 days ]Proportion of deaths from all causes
- Time to clinical recovery [ Time Frame: 28 days ]Time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air), alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent) and resolution of hypoxia (defined as SpO2 ≥ 93% in room air or P/F ≥ 300 mmHg). All these improvements must be sustained for 72 hours.
- Negative conversion of COVID-19 RT-PCR from upper respiratory tract [ Time Frame: 7 days ]Proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or oropharyngeal swab.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04305457
|Contact: Lorenzo Berrafirstname.lastname@example.org|
|Contact: Lei Chong||+86 email@example.com|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114-2621|
|Contact: Lorenzo Berra, MD firstname.lastname@example.org|