RESUMEN
BACKGROUND: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected. RESULTS: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib. CONCLUSIONS: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. CLINICAL TRIALS REGISTRATION: EudraCT: 2020-001156-18.
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Fármacos Anti-VIH , COVID-19 , Infecciones por VIH , Adulto , Humanos , Tenofovir/uso terapéutico , Emtricitabina/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Tratamiento Farmacológico de COVID-19 , DexametasonaAsunto(s)
Enteritis/diagnóstico , Eosinofilia/diagnóstico , Gastritis/diagnóstico , Corticoesteroides/uso terapéutico , Adulto , Anciano , Biopsia , Diagnóstico Precoz , Enteritis/diagnóstico por imagen , Enteritis/tratamiento farmacológico , Eosinofilia/diagnóstico por imagen , Eosinofilia/tratamiento farmacológico , Femenino , Gastritis/diagnóstico por imagen , Gastritis/tratamiento farmacológico , Gastroscopía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
OBJECTIVE: To analyze the effects of a short course of methyl-prednisolone pulses (MP) during the second week of disease (week-2) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Comparative observational study using data collected from routine care at Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain in patients with COVID-19 pneumonia. We compared patients who received week-2-MP (125-250 mg/d x3) with those who did not, with the end-points time to death and time to death or endotracheal intubation. RESULTS: We included 242 patients with COVID-19 pneumonia and elevated inflammatory markers at admission. Sixty-one patients (25%) received week-2-MP. Twenty-two patients (9%) died and 31 (12.8%) suffered death or intubation. The adjusted HRs for death and death or intubation for patients in the week-2-MP group were 0.35 (95%CI 0.11 to 1.06, p = 0.064) and 0.33 (95%CI 0.13 to 0.84, p = 0.020), respectively. These differences were specifically seen in the subcohort of patients with a SpO2/FiO2 at day 7 lower than 353 (adjusted HR 0.31, 95% CI 0.08 to 1.12, p = 0.073 and HR 0.34, 95%CI 0.12 to 0.94, p = 0.038, respectively) but not in patients with higher SpO2/FiO2. Patients receiving out-of-week-2-MP, non-pulse glucocorticoids or no glucocorticoids had an increased adjusted risk for both outcomes compared with week-2-MP group: HR 5.04 (95% CI 0.91-27.86), HR 10.09 (95% CI 2.14-47.50), HR 4.14 (95% CI 0.81-21.23), respectively, for death; HR 7.38 (95% CI 1.86-29.29), HR 13.71 (95% CI 3.76-50.07), HR 3.58 (95% CI 0.89-14.32), respectively, for death or intubation. These differences were significant only in the subgroup with low SpO2/FiO2. CONCLUSIONS: Week-2-MP are effective in improving the prognosis of patients with COVID-19 pneumonia with features of inflammatory activity and respiratory deterioration entering the second week of disease. The recognition of this high-risk population should prompt early use of MP at this point.
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Infecciones por Coronavirus/diagnóstico , Metilprednisolona/administración & dosificación , Neumonía Viral/diagnóstico , Anciano , COVID-19 , Infecciones por Coronavirus/patología , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inflamación , Intubación Intratraqueal , Masculino , Metilprednisolona/farmacología , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Oxígeno/sangre , Pandemias , Neumonía Viral/patología , Pronóstico , Estudios Retrospectivos , Riesgo , Factores de Riesgo , España , Factores de TiempoRESUMEN
No disponible
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Humanos , Femenino , Adulto , Anciano , Eosinofilia/complicaciones , Gastroenteritis/complicaciones , Laparoscopía , Corticoesteroides/uso terapéuticoAsunto(s)
Encefalitis por Herpes Simple/complicaciones , Fiebre/etiología , Cefalea/etiología , Imagen por Resonancia Magnética , Agitación Psicomotora/etiología , Convulsiones/etiología , Tomografía Computarizada por Rayos X , Adulto , Encefalitis por Herpes Simple/diagnóstico , Encefalitis por Herpes Simple/diagnóstico por imagen , Humanos , MasculinoRESUMEN
No disponible
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Adulto , Masculino , Humanos , Tomografía Computarizada por Rayos X , Imagen por Resonancia Magnética , Agitación Psicomotora , Fiebre , Cefalea , Convulsiones , Encefalitis por Herpes SimpleRESUMEN
No disponible
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Adulto , Femenino , Humanos , Resistencia a Múltiples Medicamentos , Estreptomicina , Rifampin , Negativa del Paciente al Tratamiento , Infecciones Oportunistas Relacionadas con el SIDA , Resultado Fatal , Mycobacterium kansasii , Farmacorresistencia Microbiana , Isoniazida , Etambutol , Eritromicina , Quimioterapia Combinada , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas , Ácido AminosalicílicoRESUMEN
No disponible