ABSTRACT
Background: Whether ivermectin, with a maximum targeted dose of 600 mug/ 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, maximum targeted dose of 600 mug/kg, daily for 6 days compared with placebo for the treatment of early mild to moderate COVID-19. Method(s): ACTIV-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 receive ivermectin, with a maximum targeted dose of 600 mug/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. Result(s): Among 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. Conclusion(s): Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 mug/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. Primary and secondary outcomes.
ABSTRACT
Background. The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the United States with mild-to-moderate symptomatic coronavirus disease 2019 (COVID-19) is unknown. We evaluated the efficacy of ivermectin 400 mug/kg daily for 3 days compared with placebo for the treatment of early mild-to-moderate COVID-19. Methods. ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial to evaluate repurposed therapies in outpatients with mild-to-moderate COVID-19. Non-hospitalized adults age >= 30 years with confirmed COVID-19, experiencing >= 2 symptoms of acute infection for <= 7 days were randomized to receive ivermectin 400 mug/kg daily for 3 days or placebo. The main outcome measure was time to sustained recovery, defined as achieving at least 3 consecutive days without symptoms. Secondary outcomes included a composite of hospitalization or death by day 28. Results. Of the 3457 participants who consented to be evaluated for inclusion in the ivermectin arm, 1591 were eligible for this study arm, randomized to receive ivermectin 400 mug/kg (n=817) or placebo (n=774), and received study drug. Of those enrolled, 47% reported receiving at least 2 doses of SARS-CoV-2 vaccination. The posterior probability for any improvement in time to recovery was 0.91 (hazard ratio 1.07, 95% credible interval 0.96-1.17). The posterior probability of this benefit exceeding 24 hours was less than 0.01, as measured by the difference in mean time unwell. Hospitalizations or deaths were uncommon (ivermectin [n=10];placebo [n=9]). Ivermectin at 400 mug/kg was safe and without serious adverse events as compared with placebo (ivermectin [n=10];placebo [n=9]). Conclusion. Ivermectin dosed at 400 mug/kg daily for 3 days resulted in less than one day of shortening of symptoms and did not lower incidence of hospitalization or death among outpatients with COVID-19 in the United States during the delta and omicron variant time periods.
ABSTRACT
Background: To achieve global hepatitis C virus (HCV) elimination by 2030, 80% of the ∼71 million people with chronic HCV need to be treated, necessitating simplification of treatment delivery and associated laboratory monitoring without compromising efficacy or safety. The COVID-19 pandemic has further highlighted the need for innovative models that minimize face-toface contact. Methods: ACTG A5360 is a single-arm, open-label trial to evaluate safety and efficacy of a minimal monitoring (MINMON) approach to HCV therapy in treatment-naïve persons with no evidence of decompensated cirrhosis. All participants received a single-tablet, fixed-dose regimen of sofosbuvir/velpatasvir for 12 weeks. MINMON included: (1) no genotyping;(2) all tablets dispensed at entry;(3) no on-treatment visits/labs;and (4) two remote contacts at Weeks 4 (adherence assessment) and 22 (scheduling sustained virology response [SVR] visit). Unplanned visits for participant concerns (related/unrelated to an adverse event [AE]) were allowed. SVR is defined as HCV RNA <lower limit of quantification at least 22 weeks after treatment initiation (missing HCV RNA = failure). 95% confidence intervals (CI) for SVR used Wilson's Score. Results: 400 participants were enrolled from 10/2018-07/2019 at 38 sites in five countries across 4 continents;399 initiated treatment. Median age was 47 years, 138 (35%) were cisgender women, 22 (6%) self-identified across the transgender spectrum, and 166 (42%) were White. At entry, 34 (9%) had compensated cirrhosis (FIB-4 ≥3.25) and 166 (42%) had HIV co-infection. Remote contact was successful at Weeks 4 and 22 for 394 (99%) and 335 (84%) participants, respectively. HCV RNA for SVR was available for 396 participants. Overall, 95% (379/399) achieved SVR (95% CI: 92.4%, 96.7%);SVR by country, biological sex, gender identity, age, cirrhosis status, HIV co-infection status and injection drug use are presented in Figure. Fifteen (3.8%) participants had unplanned visits;3 were AE related and 6 were related to abnormalities during screening. Serious AE events through Week 24 visit were reported in 14 (3.5%) participants;none were treatment related or resulted in death. Conclusion: In a diverse, global patient population, the MINMON approach to HCV treatment delivery was safe and achieved SVR comparable to current standards. Wider adoption of this approach coupled with innovative casefinding strategies may facilitate HCV elimination while minimizing in-person appointments and resource use.