Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution
BackgroundManaging the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease.MethodsWe designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 day...
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1156603/full |
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| author | Jesus Garcia-Donas Diego Martínez-Urbistondo Kyra Velázquez Kennedy Paula Villares Arántzazu Barquin Andrea Dominguez Juan Francisco Rodriguez-Moreno Elena Caro Rafael Suarez del Villar Estanislao Nistal-Villan Estanislao Nistal-Villan Monica Yagüe Maria Ortiz Maria Barba Sergio Ruiz-Llorente Miguel Quiralte Massimiliano Zanin Cristina Rodríguez Paloma Navarro Pedro Berraondo Pedro Berraondo Pedro Berraondo Rodrigo Madurga |
| author_facet | Jesus Garcia-Donas Diego Martínez-Urbistondo Kyra Velázquez Kennedy Paula Villares Arántzazu Barquin Andrea Dominguez Juan Francisco Rodriguez-Moreno Elena Caro Rafael Suarez del Villar Estanislao Nistal-Villan Estanislao Nistal-Villan Monica Yagüe Maria Ortiz Maria Barba Sergio Ruiz-Llorente Miguel Quiralte Massimiliano Zanin Cristina Rodríguez Paloma Navarro Pedro Berraondo Pedro Berraondo Pedro Berraondo Rodrigo Madurga |
| author_sort | Jesus Garcia-Donas |
| collection | DOAJ |
| description | BackgroundManaging the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease.MethodsWe 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.ParticipantsPatients admitted due to COVID-19 infection with mild disease.ResultsUp 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.ConclusionsRuxolitinib 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 registrationhttps://clinicaltrials.gov/, identifier NCT04348695. |
| first_indexed | 2024-04-09T17:31:14Z |
| format | Article |
| id | doaj.art-3ee849271a0c45228839d81a26042e68 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T17:31:14Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3ee849271a0c45228839d81a26042e682023-04-18T05:24:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11566031156603Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolutionJesus Garcia-Donas0Diego Martínez-Urbistondo1Kyra Velázquez Kennedy2Paula Villares3Arántzazu Barquin4Andrea Dominguez5Juan Francisco Rodriguez-Moreno6Elena Caro7Rafael Suarez del Villar8Estanislao Nistal-Villan9Estanislao Nistal-Villan10Monica Yagüe11Maria Ortiz12Maria Barba13Sergio Ruiz-Llorente14Miguel Quiralte15Massimiliano Zanin16Cristina Rodríguez17Paloma Navarro18Pedro Berraondo19Pedro Berraondo20Pedro Berraondo21Rodrigo Madurga22Gynecological, Genitourinary and Skin Cancer Unit HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Department of Basic Medical Sciences, Hospital Universitario HM Sanchinarro, HM Hospitales, Institute of Applied Molecular Medicine (IMMA), Facultad de Medicina, Universidad San Pablo CEU, CEU Universities, Madrid, SpainInternal Medicine Service Hospital HM Sanchinarro, Madrid, SpainHematology Department, Universitario Hospital Ramon y Cajal, Madrid, SpainInternal Medicine Service Hospital HM Sanchinarro, Madrid, SpainGynecological, Genitourinary and Skin Cancer Unit HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Department of Basic Medical Sciences, Hospital Universitario HM Sanchinarro, HM Hospitales, Institute of Applied Molecular Medicine (IMMA), Facultad de Medicina, Universidad San Pablo CEU, CEU Universities, Madrid, SpainInternal Medicine Service Hospital HM Sanchinarro, Madrid, SpainGynecological, Genitourinary and Skin Cancer Unit HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Department of Basic Medical Sciences, Hospital Universitario HM Sanchinarro, HM Hospitales, Institute of Applied Molecular Medicine (IMMA), Facultad de Medicina, Universidad San Pablo CEU, CEU Universities, Madrid, SpainInternal Medicine Service Hospital HM Sanchinarro, Madrid, SpainInternal Medicine Service Hospital HM Sanchinarro, Madrid, SpainMicrobiology Section, Dpto. CC, Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, SpainFacultad de Medicina, Instituto de Medicina Molecular Aplicada (IMMA), Universidad San Pablo-CEU, Madrid, SpainLaboratory of Innovation in Oncology HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Department of Basic Medical Sciences, Facultad de Medicina, Hospital Universitario HM Sanchinarro, HM Hospitales, Institute of Applied Molecular Medicine (IMMA), Universidad San Pablo CEU, CEU Universities, Madrid, SpainClinical Trials Pharmacy, Clara Campal Comprehensive Cancer Center, Hospital Universitario de Sanchinarro, Madrid, SpainLaboratory of Innovation in Oncology HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Department of Basic Medical Sciences, Facultad de Medicina, Hospital Universitario HM Sanchinarro, HM Hospitales, Institute of Applied Molecular Medicine (IMMA), Universidad San Pablo CEU, CEU Universities, Madrid, SpainLaboratory of Innovation in Oncology HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Department of Basic Medical Sciences, Facultad de Medicina, Hospital Universitario HM Sanchinarro, HM Hospitales, Institute of Applied Molecular Medicine (IMMA), Universidad San Pablo CEU, CEU Universities, Madrid, SpainLaboratory of Innovation in Oncology HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Department of Basic Medical Sciences, Facultad de Medicina, Hospital Universitario HM Sanchinarro, HM Hospitales, Institute of Applied Molecular Medicine (IMMA), Universidad San Pablo CEU, CEU Universities, Madrid, SpainInstituto de Física Interdisciplinar y Sistemas Complejos IFISC (CSIC-UIB), Palma de Mallorca, SpainGrupo de Cáncer Endocirno, Centro Nacional de Investigaciones Oncológicas, Madrid, SpainLaboratory of Innovation in Oncology HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Department of Basic Medical Sciences, Facultad de Medicina, Hospital Universitario HM Sanchinarro, HM Hospitales, Institute of Applied Molecular Medicine (IMMA), Universidad San Pablo CEU, CEU Universities, Madrid, Spain0Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain1Navarra Institute for Health Research (IDISNA), Pamplona, Spain2Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain3Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Madrid, SpainBackgroundManaging the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease.MethodsWe 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.ParticipantsPatients admitted due to COVID-19 infection with mild disease.ResultsUp 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.ConclusionsRuxolitinib 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 registrationhttps://clinicaltrials.gov/, identifier NCT04348695.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1156603/fullCOVID19SARS-Cov-2cytokine stormruxolitinibsimvastatinclinical trial |
| spellingShingle | Jesus Garcia-Donas Diego Martínez-Urbistondo Kyra Velázquez Kennedy Paula Villares Arántzazu Barquin Andrea Dominguez Juan Francisco Rodriguez-Moreno Elena Caro Rafael Suarez del Villar Estanislao Nistal-Villan Estanislao Nistal-Villan Monica Yagüe Maria Ortiz Maria Barba Sergio Ruiz-Llorente Miguel Quiralte Massimiliano Zanin Cristina Rodríguez Paloma Navarro Pedro Berraondo Pedro Berraondo Pedro Berraondo Rodrigo Madurga Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution Frontiers in Immunology COVID19 SARS-Cov-2 cytokine storm ruxolitinib simvastatin clinical trial |
| title | Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution |
| title_full | Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution |
| title_fullStr | Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution |
| title_full_unstemmed | Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution |
| title_short | Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution |
| title_sort | randomized phase ii clinical trial of ruxolitinib plus simvastatin in covid19 clinical outcome and cytokine evolution |
| topic | COVID19 SARS-Cov-2 cytokine storm ruxolitinib simvastatin clinical trial |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1156603/full |
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