ABSTRACT
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.
Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Adult , Humans , Tenofovir/therapeutic use , Emtricitabine/therapeutic use , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , COVID-19 Drug Treatment , DexamethasoneSubject(s)
Enteritis/diagnosis , Eosinophilia/diagnosis , Gastritis/diagnosis , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Biopsy , Early Diagnosis , Enteritis/diagnostic imaging , Enteritis/drug therapy , Eosinophilia/diagnostic imaging , Eosinophilia/drug therapy , Female , Gastritis/diagnostic imaging , Gastritis/drug therapy , Gastroscopy , Humans , Male , Middle Aged , Recurrence , Tomography, X-Ray Computed , UltrasonographyABSTRACT
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.
Subject(s)
Coronavirus Infections/diagnosis , Methylprednisolone/administration & dosage , Pneumonia, Viral/diagnosis , Aged , COVID-19 , Coronavirus Infections/pathology , Female , Glucocorticoids/therapeutic use , Humans , Inflammation , Intubation, Intratracheal , Male , Methylprednisolone/pharmacology , Methylprednisolone/therapeutic use , Middle Aged , Oxygen/blood , Pandemics , Pneumonia, Viral/pathology , Prognosis , Retrospective Studies , Risk , Risk Factors , Spain , Time FactorsABSTRACT
No disponible
Subject(s)
Humans , Female , Adult , Aged , Eosinophilia/complications , Gastroenteritis/complications , Laparoscopy , Adrenal Cortex Hormones/therapeutic useSubject(s)
Encephalitis, Herpes Simplex/complications , Fever/etiology , Headache/etiology , Magnetic Resonance Imaging , Psychomotor Agitation/etiology , Seizures/etiology , Tomography, X-Ray Computed , Adult , Encephalitis, Herpes Simplex/diagnosis , Encephalitis, Herpes Simplex/diagnostic imaging , Humans , MaleABSTRACT
No disponible
Subject(s)
Adult , Male , Humans , Tomography, X-Ray Computed , Magnetic Resonance Imaging , Psychomotor Agitation , Fever , Headache , Seizures , Encephalitis, Herpes SimplexABSTRACT
No disponible
Subject(s)
Adult , Female , Humans , Drug Resistance, Multiple , Streptomycin , Rifampin , Treatment Refusal , AIDS-Related Opportunistic Infections , Fatal Outcome , Mycobacterium kansasii , Drug Resistance, Microbial , Isoniazid , Ethambutol , Erythromycin , Drug Therapy, Combination , Microbial Sensitivity Tests , Mycobacterium Infections, Nontuberculous , Aminosalicylic AcidABSTRACT
No disponible