دورية أكاديمية
Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution
| العنوان: | Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution |
|---|---|
| المؤلفون: | García-Donas, Jesús, Martínez-Urbistondo, Diego, Velázquez Kennedy, Kyra, Villares, Paula, Barquin, Arántzazu, Domínguez, Andrea, Rodríguez-Moreno, Juan Francisco, Caro, Elena, Suárez del Villar, Rafael, Nistal-Villan, Estanislao, Yagüe, Mónica, Ortiz, Maria, Barba, Maria, Ruiz-Llorente, Sergio, Quiralte, Miguel, Zanin, Massimiliano, Rodríguez, Cristina, Navarro, Paloma, Berraondo, Pedro, Madurga, Rodrigo |
| المساهمون: | Novartis, Instituto de Salud Carlos III, European Research Council, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Nafarroako Gobernua |
| بيانات النشر: | Frontiers Media |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Simvastatin, COVID19, SARS-Cov-2, Clinical trial, Cytokine storm, Ruxolitinib |
| الوصف: | [Background] Managing the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease. ; [Methods] We designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 days followed by 10 mg BID for 7 days) plus simvastatin (40 mg once a day for 14 days), could reduce the incidence of respiratory insufficiency in COVID-19. 48 cytokines were correlated with clinical outcome. ; [Participants] Patients admitted due to COVID-19 infection with mild disease. ; [Results] Up to 92 were included. Mean age was 64 ± 17, and 28 (30%) were female. 11 (22%) patients in the control arm and 6 (12%) in the experimental arm reached an OSCI grade of 5 or higher (p = 0.29). Unsupervised analysis of cytokines detected two clusters (CL-1 and CL-2). CL-1 presented a higher risk of clinical deterioration vs CL-2 (13 [33%] vs 2 [6%] cases, p = 0.009) and death (5 [11%] vs 0 cases, p = 0.059). Supervised Machine Learning (ML) analysis led to a model that predicted patient deterioration 48h before occurrence with a 85% accuracy. ; [Conclusions] Ruxolitinib plus simvastatin did not impact the outcome of COVID-19. Cytokine profiling identified patients at risk of severe COVID-19 and predicted clinical deterioration. ; [Trial registration] https://clinicaltrials.govTest/, identifier NCT04348695. ; The Ruxo-Sim trial has been funded by Novartis INC through an unrestricted grant. Novartis also provided ruxolitinib. Novartis did not play any role in study design, analysis or communication. Cytokine analysis has been mainly funded by the Instituto de Salud Carlos III through Fondos COVID-19 (COV20/00211). Additionally, the project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 851255). MZ acknowledges the María de Maeztu project CEX2021-001164-M funded by the MCIN/AEI/10.13039/501100011033. PB received ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1664-3224 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/EC/H2020/851255; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2021-001164-M; Publisher's version; García-Donas, Jesús; Martínez-Urbistondo, Diego; Velázquez Kennedy, Kyra; Villares, Paula; Barquin, Arántzazu; Domínguez, Andrea; Rodríguez-Moreno, Juan Francisco; Caro, Elena; Suárez del Villar, Rafael; Nistal-Villan, Estanislao; Yagüe, Mónica; Ortiz, Maria; Barba, Maria; Ruiz-Llorente, Sergio; Quiralte, Miguel; Zanin, Massimiliano; Rodríguez, Cristina; Navarro, Paloma; Berraondo, Pedro; Madurga, Rodrigo; 2023; DataSheet_1_Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution.pdf [Dataset]; Figshare; https://doi.org/10.3389/fimmu.2023.1156603.s001Test; Navarro, Paloma; Berraondo, Pedro; Madurga, Rodrigo; 2023; Table_1_Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution.xlsx [Dataset]; Figshare; https://doi.org/10.3389/fimmu.2023.1156603.s002Test; https://doi.org/10.3389/fimmu.2023.1156603Test; Sí; Frontiers in Immunology 14: 1156603 (2023); CEX2021-001164-M; http://hdl.handle.net/10261/352169Test; http://dx.doi.org/10.13039/100004336Test; http://dx.doi.org/10.13039/501100011033Test; http://dx.doi.org/10.13039/501100000781Test; http://dx.doi.org/10.13039/501100004587Test; http://dx.doi.org/10.13039/501100004837Test; 2-s2.0-85159553059; https://api.elsevier.com/content/abstract/scopus_id/85159553059Test |
| DOI: | 10.3389/fimmu.2023.1156603 |
| DOI: | 10.13039/100004336 |
| DOI: | 10.13039/501100011033 |
| DOI: | 10.13039/501100000781 |
| DOI: | 10.13039/501100004587 |
| DOI: | 10.13039/501100004837 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2023.115660310.13039/10000433610.13039/50110001103310.13039/50110000078110.13039/50110000458710.13039/50110000483710.3389/fimmu.2023.1156603.s00110.3389/fimmu.2023.1156603.s002Test http://hdl.handle.net/10261/352169Test https://api.elsevier.com/content/abstract/scopus_id/85159553059Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.1941FC9E |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16643224 |
|---|---|
| DOI: | 10.3389/fimmu.2023.1156603 |