ABSTRACT
Background: Some in vitro, animal, and epidemiological data suggest that tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) might be an efficacious treatment for COVID-19 Methods: In a multicenter open-label, pragmatic, randomized trial in 25 hospitals in Spain we included participants with symptomatic SARS-CoV-2 detected by PCR or antigenic test, with a creatinine clearance > 60 mL/min, > 60 years or younger if they had at least 2 comorbidities (hypertension, obesity, diabetes, cirrhosis, chronic neurologic disease, active cancer, heart failure, coronary heart disease or COPD). Participants were randomized to receive or not TDF/FTC. Randomization was stratified by age group, symptoms duration (< or ≥ 5 days) and health care setting (hospitalized, long-term care facility, ambulatory). Primary outcome was 28 days mortality. Secondary outcomes were disease progression (increased O2 requirements, need for mechanical ventilation or increase in medical therapy: steroid dose, need for tocilizumab). At any moment during the trial participants with room air O2 saturation < 95% and ≥ 1 increased inflammatory biomarker could be randomized to dexamethasone (D) or dexamethasone plus baricitinib (DB) Results: 355 participants included (TDF/FTC n=177, no TDF/FTC n=178), median age 67 years (IQR 62-73), male (64.5%), median days of symptoms 8 (IQR 5-10), 29% with < 5 days of symptoms, 96.9% hospitalized, 35.5% with 1 and 36.6 % with ≥ 2 comorbidities (62.8% hypertension, 9.3% diabetes, 1.7% obesity), median room air SaO2 95% (IQR 94-96), 63% receiving O2 and 11.8% Remdesivir. 74% of participants were simultaneously randomized to D or DB. There were not statistically significant differences in endpoints in participants not treated vs.treated with TDF/FTC: mortality 2.2%/4.0%, disease progression 23.6%/22.0%, deferred randomization to D or DB 6.7%/6.2%, mechanical ventilation (invasive or noninvasive) 22.5%/20.3%, days since randomization until discharge (median [IQR]) 7 [5,14]/6 [4,12], discharge before 28 days 91.9%/89.7%. By Cox regression Hazard Ratio (95% CI) of 28-day mortality was 1.96 (0.55-7.01) for participants treated with TDF/FTC. Serious adverse events occurred in 6.18%/5.65% of participants not treated/treated with TDF/FTC. Adverse events leading to TDF/FTC discontinuation occurred in 2.26%. Conclusion: In this clinical trial of high-risk patients with COVID-19 TDF/FTC did not improve disease outcomes. Overall mortality was unexpectedly low.
ABSTRACT
Background: Remdesivir (RDV) shortens time to recovery time in patients with severe COVID-19. Its effect in patients with moderate COVID-19 remains unclear. Methods: We conducted an open-label, phase 3 trial (NCT04252664) involving hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned 1:1:1 to receive up to 5d or 10d of RDV with standard of care (SoC), or SoC alone;patients could be discharged prior to completing per-protocol assigned treatment duration. RDV was dosed intravenously at 200 mg on d1, 100 mg daily thereafter. Patients were evaluated daily while hospitalized, and via telephone if discharged. The primary endpoint was clinical status on d11 assessed on a 7-point ordinal scale. Results regarding the primary endpoint are expected to be published before IDWeek 2020;we plan to present d28 results at the meeting. Results: In total, 584 patients underwent randomization and started their assigned treatment (191, 5d RDV;193, 10d RDV;200, SoC). By d11, 3 2 point improvement on the ordinal scale occurred in 70% of patients in the 5d arm, 65% in the 10d arm, and 61% in the SoC arm. Patients in the 5d RDV arm were significantly more likely to have an improvement in clinical status than those receiving SoC (odds ratio [OR], 1.65;95% confidence interval [CI], 1.09-2.48;P=0.017);OR of improvement for the 10d RDV arm compared to SoC was 1.31 (95% CI, 0.88-1.95];p=0.183). This improvement in the 5-day arm over the SOC arm was noted from d6 through d11. We observed a peak of discharges corresponding with the assigned treatment duration of RDV, with increased discharges at d6 in the 5-day arm and at d11 in the 10-day arm. A worsening of clinical status of ≥ 1 point in the ordinal scale was observed more commonly in the SoC am (n=19, 10%) versus the 5d RDV (n=7, 4%) and 10d RDV (n=9, 5%). Conclusion: RDV for up to 5 days was superior to SoC in improving the clinical status of patients with moderate COVID-19 by d11. We will report d28 outcomes at the meeting. (Table Presented).