Nitric Oxide Gas Inhalation Therapy in Spontaneous Breathing Patients With Mild/Moderate COVID19 Infection: a Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 主要终点
- Reduction in the incidence of intubation and mechanical ventilation
研究概览
简要总结
The scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (COVID-19) originated in China in December 2019. At present, there are no proven interventions to prevent progression of the disease. Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on COVID-19 due to the genomic similarities between this two coronaviruses. In this study we will test whether inhaled NO therapy prevents progression in patients with mild to moderate COVID-19 disease.
详细描述
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 progress 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 morbility 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 eukaryotic cells.Based on the genetic similarities between the two viruses, similar effects of NO on COVID-19 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 COVID-19 related disease, when administered at an early stage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Laboratory confirmed COVID19 infection defined with a positive RT-PCR from any specimen.
- •Hospital admission with at least one of the following:
- •fever ≥ 36.6 °C from axillary site; or ≥ 37.2°C from oral site; or ≥ 37.6°C from tympanic or rectal site.
- •Respiratory rate ≥ 24 bpm
- •Spontaneous breathing with or without hypoxia of any degree. Gas exchange and ventilation maybe assisted by any continuous continuous airway pressure (CPAP), or any system of Non Invasive Ventilation (NIV), with Positive End-Expiratory Pressure (PEEP) ≤ 10 cmH2O.
- •≤ 8 days since onset of the symptoms
排除标准
- •Pregnancy, or positive pregnancy test in a predose examination
- •Open tracheostomy
- •Therapy with high flow nasal cannula
- •Clinical controindication, as deemed by the attending physician
研究组 & 干预措施
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.
干预措施: Nitric Oxide (Drug)
结局指标
主要结局
Reduction in the incidence of intubation and mechanical ventilation
时间窗: 28 days
The primary outcome will be the proportion of patients with mild COVID2019 who deteriorate to a severe form of the disease requiring intubation and mechanical ventilation. 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.
次要结局
- Negative conversion of COVID-19 RT-PCR from upper respiratory tract(7 days)
- Mortality(28 days)
- Time to clinical recovery(28 days)
研究者
chonglei
M.D. & Ph.D.
Xijing Hospital