Frontiers in immunology · 2023
Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution.
Рандомизированное исследованиеКлиническое исследование II фазыСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Garcia-Donas Jesus, Martínez-Urbistondo Diego, Velázquez Kennedy Kyra, Villares Paula, Barquin Arántzazu, Dominguez Andrea, Rodriguez-Moreno Juan Francisco, Caro Elena, Suarez Del Villar Rafael, Nistal-Villan Estanislao, Yagüe Monica, Ortiz Maria, Barba Maria, Ruiz-Llorente Sergio, Quiralte Miguel, Zanin Massimiliano, Rodríguez Cristina, Navarro Paloma, Berraondo Pedro, Madurga Rodrigo
Аннотация
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.gov/, identifier NCT04348695.
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.gov/, identifier NCT04348695.