Nikolay O. Kamenshchikov , Bijan Safaee Fakhr , Igor V. Kravchenko , Andrey Yu Dish , Yuri K. Podoksenov , Boris N. Kozlov , Tatiana P. Kalashnikova , Mark A. Tyo , Nina D. Anfinogenova , Alla A. Boshchenko , Lorenzo Berra
{"title":"在自主呼吸的 COVID-19 患者中持续吸入低剂量和高剂量一氧化氮的评估：随机对照试验","authors":"Nikolay O. Kamenshchikov , Bijan Safaee Fakhr , Igor V. Kravchenko , Andrey Yu Dish , Yuri K. Podoksenov , Boris N. Kozlov , Tatiana P. Kalashnikova , Mark A. Tyo , Nina D. Anfinogenova , Alla A. Boshchenko , Lorenzo Berra","doi":"10.1016/j.niox.2024.06.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Inhaled nitric oxide (iNO) showed to improve oxygenation at low doses by reducing intrapulmonary shunt and to display antiviral properties at high doses. To assess the safety and potential benefits, we designed an exploratory clinical trial comparing low-dose with intermittent high-dose iNO to only intermittent high-dose iNO in hypoxemic COVID-19 patients.</p></div><div><h3>Methods</h3><p>In this single-center interventional non-inferiority randomized trial (<span>ClinicalTrials.gov</span><svg><path></path></svg>, NCT04476992), twenty oxygen-dependent COVID-19 patients were randomly assigned to the high-dose (200 ppm for 30 min) + continuous low-dose (20 ppm) iNO group (iNO<sub>200/20</sub>) or the high-dose iNO group (iNO<sub>200</sub>). Methemoglobinemia (MetHb) assessed 48 h after iNO initiation was the primary endpoint. Reverse-transcription polymerase chain reaction for SARS-CoV-2, inflammatory markers during hospitalization, and heart ultrasounds during the iNO<sub>200</sub> treatments were evaluated.</p></div><div><h3>Results</h3><p>MetHb difference between iNO groups remained within the non-inferiority limit of 3 %, indicating comparable treatments despite being statistically different (p-value<0.01). Both groups presented similar SpO<sub>2</sub>/FiO<sub>2</sub> ratio at 48 h (iNO<sub>200</sub> vs. iNO<sub>200/20</sub> 341[334–356] vs. 359 [331–380], respectively, p-value = 0.436). Both groups showed the same time to SARS-CoV-2 negativization, hospital length of stay, and recovery time. iNO-treated patients showed quicker SARS-CoV-2 negativization compared to a similar group of non-iNO patients (HR 2.57, 95%CI 1.04–6.33). During the 228 treatments, iNO<sub>200</sub> and iNO<sub>200/20</sub> groups were comparable for safety, hemodynamic stability, and respiratory function improvement.</p></div><div><h3>Conclusions</h3><p>iNO<sub>200/20</sub> and iNO<sub>200</sub> are equally safe in non-intubated patients with COVID-19-induced respiratory failure with regards to MetHb and NO<sub>2</sub>. Larger studies should investigate whether iNO<sub>200/20</sub> leads to better outcomes compared to non-iNO treated patients.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Assessment of continuous low-dose and high-dose burst of inhaled nitric oxide in spontaneously breathing COVID-19 patients: A randomized controlled trial\",\"authors\":\"Nikolay O. Kamenshchikov , Bijan Safaee Fakhr , Igor V. Kravchenko , Andrey Yu Dish , Yuri K. Podoksenov , Boris N. Kozlov , Tatiana P. Kalashnikova , Mark A. Tyo , Nina D. Anfinogenova , Alla A. Boshchenko , Lorenzo Berra\",\"doi\":\"10.1016/j.niox.2024.06.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Inhaled nitric oxide (iNO) showed to improve oxygenation at low doses by reducing intrapulmonary shunt and to display antiviral properties at high doses. To assess the safety and potential benefits, we designed an exploratory clinical trial comparing low-dose with intermittent high-dose iNO to only intermittent high-dose iNO in hypoxemic COVID-19 patients.</p></div><div><h3>Methods</h3><p>In this single-center interventional non-inferiority randomized trial (<span>ClinicalTrials.gov</span><svg><path></path></svg>, NCT04476992), twenty oxygen-dependent COVID-19 patients were randomly assigned to the high-dose (200 ppm for 30 min) + continuous low-dose (20 ppm) iNO group (iNO<sub>200/20</sub>) or the high-dose iNO group (iNO<sub>200</sub>). Methemoglobinemia (MetHb) assessed 48 h after iNO initiation was the primary endpoint. Reverse-transcription polymerase chain reaction for SARS-CoV-2, inflammatory markers during hospitalization, and heart ultrasounds during the iNO<sub>200</sub> treatments were evaluated.</p></div><div><h3>Results</h3><p>MetHb difference between iNO groups remained within the non-inferiority limit of 3 %, indicating comparable treatments despite being statistically different (p-value<0.01). Both groups presented similar SpO<sub>2</sub>/FiO<sub>2</sub> ratio at 48 h (iNO<sub>200</sub> vs. iNO<sub>200/20</sub> 341[334–356] vs. 359 [331–380], respectively, p-value = 0.436). Both groups showed the same time to SARS-CoV-2 negativization, hospital length of stay, and recovery time. iNO-treated patients showed quicker SARS-CoV-2 negativization compared to a similar group of non-iNO patients (HR 2.57, 95%CI 1.04–6.33). During the 228 treatments, iNO<sub>200</sub> and iNO<sub>200/20</sub> groups were comparable for safety, hemodynamic stability, and respiratory function improvement.</p></div><div><h3>Conclusions</h3><p>iNO<sub>200/20</sub> and iNO<sub>200</sub> are equally safe in non-intubated patients with COVID-19-induced respiratory failure with regards to MetHb and NO<sub>2</sub>. Larger studies should investigate whether iNO<sub>200/20</sub> leads to better outcomes compared to non-iNO treated patients.</p></div>\",\"PeriodicalId\":19357,\"journal\":{\"name\":\"Nitric oxide : biology and chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-06-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nitric oxide : biology and chemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1089860324000788\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nitric oxide : biology and chemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1089860324000788","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Assessment of continuous low-dose and high-dose burst of inhaled nitric oxide in spontaneously breathing COVID-19 patients: A randomized controlled trial
Background
Inhaled nitric oxide (iNO) showed to improve oxygenation at low doses by reducing intrapulmonary shunt and to display antiviral properties at high doses. To assess the safety and potential benefits, we designed an exploratory clinical trial comparing low-dose with intermittent high-dose iNO to only intermittent high-dose iNO in hypoxemic COVID-19 patients.
Methods
In this single-center interventional non-inferiority randomized trial (ClinicalTrials.gov, NCT04476992), twenty oxygen-dependent COVID-19 patients were randomly assigned to the high-dose (200 ppm for 30 min) + continuous low-dose (20 ppm) iNO group (iNO200/20) or the high-dose iNO group (iNO200). Methemoglobinemia (MetHb) assessed 48 h after iNO initiation was the primary endpoint. Reverse-transcription polymerase chain reaction for SARS-CoV-2, inflammatory markers during hospitalization, and heart ultrasounds during the iNO200 treatments were evaluated.
Results
MetHb difference between iNO groups remained within the non-inferiority limit of 3 %, indicating comparable treatments despite being statistically different (p-value<0.01). Both groups presented similar SpO2/FiO2 ratio at 48 h (iNO200 vs. iNO200/20 341[334–356] vs. 359 [331–380], respectively, p-value = 0.436). Both groups showed the same time to SARS-CoV-2 negativization, hospital length of stay, and recovery time. iNO-treated patients showed quicker SARS-CoV-2 negativization compared to a similar group of non-iNO patients (HR 2.57, 95%CI 1.04–6.33). During the 228 treatments, iNO200 and iNO200/20 groups were comparable for safety, hemodynamic stability, and respiratory function improvement.
Conclusions
iNO200/20 and iNO200 are equally safe in non-intubated patients with COVID-19-induced respiratory failure with regards to MetHb and NO2. Larger studies should investigate whether iNO200/20 leads to better outcomes compared to non-iNO treated patients.
期刊介绍：
Nitric Oxide includes original research, methodology papers and reviews relating to nitric oxide and other gasotransmitters such as hydrogen sulfide and carbon monoxide. Special emphasis is placed on the biological chemistry, physiology, pharmacology, enzymology and pathological significance of these molecules in human health and disease. The journal also accepts manuscripts relating to plant and microbial studies involving these molecules.
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