Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
JAMA. 2023 Mar 21;329(11):888-897. doi: 10.1001/jama.2023.1650.
It is unknown whether ivermectin, with a maximum targeted dose of 600 μg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19.
To evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19.
DESIGN, SETTING, AND PARTICIPANTS: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform randomized clinical trial was designed to evaluate repurposed therapies among outpatients with mild to moderate COVID-19. A total of 1206 participants older than 30 years with confirmed COVID-19 experiencing at least 2 symptoms of acute infection for less than or equal to 7 days were enrolled at 93 sites in the US from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022.
Participants were randomly assigned to receive ivermectin, with a maximum targeted dose of 600 μg/kg (n = 602) daily, or placebo (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.
Among 1206 randomized participants who received study medication or placebo, the median (IQR) age was 48 (38-58) years, 713 (59.1%) were women, and 1008 (83.5%) reported receiving at least 2 SARS-CoV-2 vaccine doses. The median (IQR) time to sustained recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (posterior probability of benefit) for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.13; P = .68). Among those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (hazard ratio, 1.0 [95% credible interval, 0.6-1.5]; P = .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.
Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo did not improve time to sustained recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19.
ClinicalTrials.gov Identifier: NCT04885530.
尚不清楚最大目标剂量为 600μg/kg 的伊维菌素能否缩短门诊轻度至中度 COVID-19 患者的症状持续时间或预防住院。
评估最大目标剂量为 600μg/kg 的伊维菌素每日 1 次、连用 6 天，与安慰剂相比，用于治疗早期轻度至中度 COVID-19 的疗效。
设计、地点和参与者：正在进行的 COVID-19 加速治疗干预和疫苗 6 （ACTIV-6）平台随机临床试验旨在评估轻度至中度 COVID-19 门诊患者中重新利用的疗法。共有 1206 名年龄大于 30 岁的参与者，在从 2022 年 2 月 16 日至 2022 年 7 月 22 日在全美 93 个地点入组，这些参与者确诊 COVID-19，且症状出现不到或等于 7 天，有至少 2 项急性感染症状，随访数据截至 2022 年 11 月 10 日。
参与者随机接受伊维菌素（最大目标剂量为 600μg/kg，n=602）或安慰剂（n=604），每日 1 次，连用 6 天。
主要结局是持续恢复的时间，定义为至少连续 3 天无症状。7 项次要结局包括 28 天内住院、死亡或紧急/急诊治疗的复合结局。
在接受研究药物或安慰剂的 1206 名随机参与者中，中位数（IQR）年龄为 48（38-58）岁，713 名（59.1%）为女性，1008 名（83.5%）报告至少接种了 2 剂 SARS-CoV-2 疫苗。伊维菌素组的中位数（IQR）持续恢复时间为 11（11-12）天，安慰剂组为 11（11-12）天。恢复时间改善的风险比（后验获益概率）为 1.02（95%可信区间，0.92-1.13；P=0.68）。在接受伊维菌素的参与者中，34 名（5.7%）住院、死亡或接受紧急或急诊治疗，而接受安慰剂的参与者中，36 名（6.0%）住院（风险比，1.0[95%可信区间，0.6-1.5]；P=0.53）。在伊维菌素组中，1 名参与者死亡，4 名参与者住院（0.8%）；安慰剂组中有 2 名参与者（0.3%）住院，无人死亡。两组不良反应均不常见。
在轻度至中度 COVID-19 的门诊患者中，与安慰剂相比，最大目标剂量为 600μg/kg 的伊维菌素每日 1 次、连用 6 天，并未改善持续恢复时间。这些发现不支持在轻度至中度 COVID-19 患者中使用伊维菌素。
ClinicalTrials.gov 标识符：NCT04885530。
