ABSTRACT
BackgroundWhether ivermectin, with a maximum targeted dose of 600 g/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) remains unknown. Our objective was to evaluate the effectiveness of ivermectin, dosed at 600 g/kg, daily for 6 days compared with placebo for the treatment of early mild to moderate COVID-19. MethodsACTIV-6, an ongoing, decentralized, randomized, double-blind, placebo-controlled, platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1206 participants age [≥]30 years with confirmed COVID-19, experiencing [≥]2 symptoms of acute infection for [≤]7 days, were enrolled from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022, at 93 sites in the US. Participants were randomized to ivermectin, with a maximum targeted dose of 600 g/kg (n=602), daily vs. placebo daily (n=604) for 6 days. The primary outcome was time to sustained recovery, defined as at least 3 consecutive days without symptoms. The 7 secondary outcomes included a composite of hospitalization, death, or urgent/emergent care utilization by day 28. ResultsAmong 1206 randomized participants who received study medication or placebo, median (interquartile range) age was 48 (38-58) years; 713 (59%) were women; and 1008 (84%) reported [≥]2 SARS-CoV-2 vaccine doses. Median time to recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (HR) (95% credible interval [CrI], posterior probability of benefit) for improvement in time to recovery was 1.02 (0.92-1.13; P[HR>1]=0.68). In those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (HR 1.0, 0.6- 1.5; P[HR<1]=0.53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups. ConclusionsAmong outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 g/kg daily for 6 days, compared with placebo did not improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial registrationClinicalTrials.gov Identifier: NCT04885530.
ABSTRACT
BackgroundThe effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic coronavirus disease 2019 (COVID-19) is unclear. DesignACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 non-hospitalized adults aged [≥]30 years with confirmed COVID-19 experiencing [≥]2 symptoms of acute infection for [≤]7 days prior to randomization were randomized to receive fluvoxamine 50 mg or placebo twice daily for 10 days. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent or emergency care visit by day 28. ResultsOf 1331 participants randomized (mean [SD] age, 48.5 [12.8] years; 57% women; 67% reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (n=614 placebo, n=674 fluvoxamine). Median time to recovery was 13 days (IQR 12-13) in the placebo group and 12 days (IQR 11-14) in the fluvoxamine group (hazard ratio [HR] 0.96, 95% credible interval [CrI] 0.86-1.07; posterior probability for benefit [HR>1]=0.22). Twenty-six participants (3.9%) in the fluvoxamine group were hospitalized or had urgent or emergency care visits compared with 23 (3.8%) in the placebo group (HR 1.1, 95% CrI 0.6-1.8; posterior probability for benefit [HR<1]=0.340). One participant in the fluvoxamine group and 2 in the placebo group were hospitalized; no deaths occurred. Adverse events were uncommon in both groups. ConclusionsTreatment with fluvoxamine 50 mg twice daily for 10 days did not improve time to recovery, compared with placebo, among outpatients with mild to moderate COVID-19. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.
ABSTRACT
ObjectiveTo determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCW). DesignMulticenter, 1:1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial. Setting34 clinical centers in the United States. Participants1360 HCW at risk for COVID-19 infection enrolled between April and November 2020. InterventionsA loading dose of HCQ 600 mg twice on Day 1 followed by 400 mg daily for 29 days or matching placebo taken orally. Main Outcome MeasureComposite of confirmed or suspected COVID-19 clinical infection by Day 30 defined as new onset fever, cough, or dyspnea and either a positive SARS-CoV-2 PCR test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). ResultsEnrollment for the study was closed before full accrual due to difficulties recruiting additional participants. The primary composite endpoint occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No statistically significant difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6% to 0.9%, p=0.20). We identified no significant safety issues. ConclusionOral HCQ taken as prescribed appeared to be safe in a group of HCW. No significant clinical benefits were observed. The study was underpowered to rule out a small but potentially important reduction in COVID-19 infections. Trial RegistrationNCT04334148
ABSTRACT
IntroductionEarly COVID-19 vaccine acceptance rates suggest that up to one-third of HCWs may be vaccine-hesitant. However, it is unclear whether hesitancy among HCWs has improved with time and if there are temporal changes whether these differ by healthcare worker role. MethodsIn October 2020, a brief survey was sent to all participants in the Healthcare Worker Exposure Response and Outcomes (HERO) Registry with a yes/no question regarding vaccination under emergency use authorization (EUA): "If an FDA emergency use-approved vaccine to prevent coronavirus/COVID-19 was available right now at no cost, would you agree to be vaccinated?" The poll was repeated in December 2020, with the same question sent to all registry participants. Willingness was defined as a "Yes" response, and hesitancy was defined as a "No" response. Participants were stratified into clinical care roles. Baseline demographics of survey respondents at each timepoint were compared using appropriate univariate statistics (chi-squared and t-tests). Analyses were descriptive, with frequencies and percentages reported for each category. ResultsOf 4882 HERO active registry participants during September 1 - October 31, 2020, 2070 (42.4%) completed the October survey, and n=1541 (31.6%) completed the December survey. 70.2% and 67.7% who were in clinical care roles, respectively. In October, 54.2% of HCWs in clinical roles said they would take an EUA-approved vaccine, which increased to 76.2% in December. The largest gain in vaccine willingness was observed among physicians, 64.0% of whom said they would take a vaccine in October, compared with 90.5% in December. Nurses were the least likely to report that they would take a vaccine in both October (46.6%) and December (66.9%). We saw no statistically significant differences in age, race/ethnicity, gender, or medical role between time points. When restricting to the 998 participants who participated at both time points, 69% were vaccine-willing at both time points; 15% were hesitant at both time points, 13% who were hesitant in October were willing in December; and 2.9% who were willing in October were hesitant in December. ConclusionsIn a set of cross-sectional surveys of vaccine acceptance among healthcare workers, willingness improved substantially over 2 calendar months during which the US had a presidential election and two vaccine manufacturers released top-line Phase 3 trial results. While improved willingness was observed in all role categories, nurses reported the most vaccine hesitancy at both time points.
ABSTRACT
BackgroundNational data from diverse institutions across the United States are critical for guiding policymakers as well as clinical and public health leaders. This study characterized a large national cohort of patients diagnosed with COVID-19 in the U.S., compared to patients diagnosed with viral pneumonia and influenza. Methods and FindingsWe captured cross-sectional information from 36 large healthcare systems in 29 U.S. states, participating in PCORnet(R), the National Patient-Centered Clinical Research Network. Patients included were those diagnosed with COVID-19, viral pneumonia and influenza in any care setting, starting from January 1, 2020. Using distributed queries executed at each participating institution, we acquired information for patients on care setting (any, ambulatory, inpatient or emergency department, mechanical ventilator), age, sex, race, state, comorbidities (assessed with diagnostic codes), and medications used for treatment of COVID-19 (hydroxychloroquine with or without azithromycin; corticosteroids, anti-interleukin-6 agents). During this time period, 24,516 patients were diagnosed with COVID-19, with 42% in an emergency department or inpatient hospital setting; 79,639 were diagnosed with viral pneumonia (53% inpatient/ED) and 163,984 with influenza (41% inpatient/ED). Among COVID-19 patients, 68% were 20 to <65 years of age, with more of the hospitalized/ED patients in older age ranges (23% 65+ years vs. 12% for COVID-19 patients in the ambulatory setting). Patients with viral pneumonia were of a similar age, and patients with influenza were much younger. Comorbidities were common, especially for patients with COVID-19 and viral pneumonia, with hypertension (32% for COVID-19 and 46% for viral pneumonia), arrhythmias (20% and 35%), and pulmonary disease (19% and 40%) the most common. Hydroxychloroquine was used in treatment for 33% and tocilizumab for 11% of COVID-19 patients on mechanical ventilators (25% received azithromycin as well). Conclusion and RelevancePCORnet leverages existing data to capture information on one of the largest U.S. cohorts to date of patients diagnosed with COVID-19 compared to patients diagnosed with viral pneumonia and influenza.
