{"title":"新型鞘氨醇-1-磷酸受体配体奥扎莫德在需要吸氧的 COVID-19 患者中的心脏安全性","authors":"","doi":"10.1016/j.cjco.2024.05.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Ozanimod is a novel immune modulator that could be useful in viral pulmonary infections by reducing lung inflammation. It is an S1P receptor ligand known to induce bradycardia and more serious adverse cardiac effects, such as atrioventricular block and QT interval prolongation. We present a substudy of the <strong>C</strong>OVID-19 <strong>Oz</strong>animod <strong>I</strong>ntervention (COZI) trial in which ozanimod was administered in acute pulmonary infection patients, to assess cardiac safety.</p></div><div><h3>Methods</h3><p>In this pilot randomized open-label trial, COVID-19 patients requiring oxygen support were randomized into 2 groups: standard-of-care + ozanimod (OZA) vs standard-of-care alone (SOC). All patients were monitored with a 14-day electrocardiogram monitor (CardioSTAT, Icentia, Quebec, QC) during their hospitalization. We evaluated the cardiac effects of ozanimod on heart rate (HR), PR interval length, and QT interval duration.</p></div><div><h3>Results</h3><p>A total of 42 patients were analyzed: 23 in the SOC group and 19 in the OZA group. Mean hourly HR over the first 10 days of treatment decreased in the OZA group, compared with that in the SOC group (<em>P</em> < 0.0001). The maximum decrease in HR occurred on day 3. The maximum decrease in HR occurred on day 3, without a significant difference between groups: 49 beats per minute (interquartile range, 42-59) in the OZA group, and 54 beats per minute (48–60) in the SOC group, <em>P</em> = 0.45. No high-degree atrioventricular block was recorded. QT and PR interval median values were within the normal range in both groups, without a significant difference.</p></div><div><h3>Conclusions</h3><p>The maximal reduction in HR occurred 3 days after the onset of ozanimod treatment in patients hospitalized for COVID-19, but it did not remain significant over the 10-day treatment period. No relevant cardiac adverse event was observed.</p></div>","PeriodicalId":36924,"journal":{"name":"CJC Open","volume":"6 9","pages":"Pages 1035-1041"},"PeriodicalIF":2.5000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589790X24002129/pdfft?md5=92f1fbffaa8f6a3a1bb60c8070785f0f&pid=1-s2.0-S2589790X24002129-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Cardiac Safety of Ozanimod Use, a Novel Sphingosine-1-Phosphate Receptor Ligand, in COVID-19 Patients Requiring Oxygen: Secondary Analysis of the COZI Randomized Clinical Trial\",\"authors\":\"\",\"doi\":\"10.1016/j.cjco.2024.05.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Ozanimod is a novel immune modulator that could be useful in viral pulmonary infections by reducing lung inflammation. It is an S1P receptor ligand known to induce bradycardia and more serious adverse cardiac effects, such as atrioventricular block and QT interval prolongation. We present a substudy of the <strong>C</strong>OVID-19 <strong>Oz</strong>animod <strong>I</strong>ntervention (COZI) trial in which ozanimod was administered in acute pulmonary infection patients, to assess cardiac safety.</p></div><div><h3>Methods</h3><p>In this pilot randomized open-label trial, COVID-19 patients requiring oxygen support were randomized into 2 groups: standard-of-care + ozanimod (OZA) vs standard-of-care alone (SOC). All patients were monitored with a 14-day electrocardiogram monitor (CardioSTAT, Icentia, Quebec, QC) during their hospitalization. We evaluated the cardiac effects of ozanimod on heart rate (HR), PR interval length, and QT interval duration.</p></div><div><h3>Results</h3><p>A total of 42 patients were analyzed: 23 in the SOC group and 19 in the OZA group. Mean hourly HR over the first 10 days of treatment decreased in the OZA group, compared with that in the SOC group (<em>P</em> < 0.0001). The maximum decrease in HR occurred on day 3. The maximum decrease in HR occurred on day 3, without a significant difference between groups: 49 beats per minute (interquartile range, 42-59) in the OZA group, and 54 beats per minute (48–60) in the SOC group, <em>P</em> = 0.45. No high-degree atrioventricular block was recorded. QT and PR interval median values were within the normal range in both groups, without a significant difference.</p></div><div><h3>Conclusions</h3><p>The maximal reduction in HR occurred 3 days after the onset of ozanimod treatment in patients hospitalized for COVID-19, but it did not remain significant over the 10-day treatment period. No relevant cardiac adverse event was observed.</p></div>\",\"PeriodicalId\":36924,\"journal\":{\"name\":\"CJC Open\",\"volume\":\"6 9\",\"pages\":\"Pages 1035-1041\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2589790X24002129/pdfft?md5=92f1fbffaa8f6a3a1bb60c8070785f0f&pid=1-s2.0-S2589790X24002129-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CJC Open\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2589790X24002129\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CJC Open","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589790X24002129","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Cardiac Safety of Ozanimod Use, a Novel Sphingosine-1-Phosphate Receptor Ligand, in COVID-19 Patients Requiring Oxygen: Secondary Analysis of the COZI Randomized Clinical Trial
Background
Ozanimod is a novel immune modulator that could be useful in viral pulmonary infections by reducing lung inflammation. It is an S1P receptor ligand known to induce bradycardia and more serious adverse cardiac effects, such as atrioventricular block and QT interval prolongation. We present a substudy of the COVID-19 Ozanimod Intervention (COZI) trial in which ozanimod was administered in acute pulmonary infection patients, to assess cardiac safety.
Methods
In this pilot randomized open-label trial, COVID-19 patients requiring oxygen support were randomized into 2 groups: standard-of-care + ozanimod (OZA) vs standard-of-care alone (SOC). All patients were monitored with a 14-day electrocardiogram monitor (CardioSTAT, Icentia, Quebec, QC) during their hospitalization. We evaluated the cardiac effects of ozanimod on heart rate (HR), PR interval length, and QT interval duration.
Results
A total of 42 patients were analyzed: 23 in the SOC group and 19 in the OZA group. Mean hourly HR over the first 10 days of treatment decreased in the OZA group, compared with that in the SOC group (P < 0.0001). The maximum decrease in HR occurred on day 3. The maximum decrease in HR occurred on day 3, without a significant difference between groups: 49 beats per minute (interquartile range, 42-59) in the OZA group, and 54 beats per minute (48–60) in the SOC group, P = 0.45. No high-degree atrioventricular block was recorded. QT and PR interval median values were within the normal range in both groups, without a significant difference.
Conclusions
The maximal reduction in HR occurred 3 days after the onset of ozanimod treatment in patients hospitalized for COVID-19, but it did not remain significant over the 10-day treatment period. No relevant cardiac adverse event was observed.