■具有宿主导向的抗病毒和免疫调节特性的重组药物在治疗COVID-19方面显示出希望,但很少有试验研究这些药物的组合。这项试验的目的是评估负担得起的有效性,广泛可用,联合使用的药物用于治疗COVID-19,这可能与低资源国家特别相关。
■我们进行了开放标签,随机化,门诊病人,2021年10月1日至2022年6月21日在泰国进行的对照试验,以评估氟伏沙明组合是否在症状发作后48小时内进行早期治疗,溴己新,赛庚啶,还有氯硝柳胺,给予确诊为轻度SARS-CoV-2感染的成年人,与标准护理相比,可以预防28天的临床恶化。参与者被随机分配接受单独的氟伏沙明治疗,氟伏沙明+溴己新,氟伏沙明+赛庚啶,氯硝柳胺+溴己新,或标准护理。使用6分序数量表测量的主要结果是9、14或28天内的临床恶化。本试验在ClinicalTrials.gov(NCT05087381)注册。
■在被招募的1900人中,共有995名参与者完成了试验.在接受氟伏沙明+溴己新治疗的患者中,没有参与者在第9天、第14天或第28天出现临床恶化(0%),氟伏沙明加赛庚啶(0%),或氯硝柳胺加溴己新(0%)。氟伏沙明组的9名参与者(5.6%)在第28天出现临床恶化,需要低流量氧气。相比之下,大多数标准治疗组参与者在第9,14和28天出现临床恶化.到第9天,标准护理组中有32.7%(110)的患者住院,无需补充氧气,但需要持续的医疗护理。到第28天,该百分比增加到37.5%(21)。此外,标准护理组中20.8%(70)的患者在第9天需要低流量氧气,12.5%(16)的患者在第28天需要无创或机械通气。在第9、14和28天,所有治疗组与标准护理组显著不同(p<0.0001)。此外,到第28天,3种2-药物治疗显著优于氟伏沙明治疗组(p<0.0001).任何研究组均未发生死亡。与标准护理相比,早在治疗的第3天,接受联合药物治疗的参与者的病毒载量显着降低(p<0.0001),血清细胞因子白细胞介素-6(IL-6)水平降低,肿瘤坏死因子-α(TNF-α),和白细胞介素-1β(IL-1β)早在治疗的第5天,到治疗第7天(p<0.0001)和白介素-8(IL-8),COVID-19(PASC)症状的急性后遗症发生率较低(p<0.0001)。标准护理组发生了23起严重不良事件,虽然氟伏沙明组仅报告了1起严重不良事件,其他组发生了零严重不良事件。
■在确诊为COVID-19的门诊患者中,早期使用这些组合进行治疗与临床恶化的可能性较低相关,随着病毒载量和血清细胞因子的显著和快速降低,PASC症状负担较低。当症状发作后不久开始时,这些再利用的药物在预防已接种和未接种的COVID-19患者的临床恶化和死亡方面具有很高的潜力.
■PedThaiSuPhai(泰国鸭子战斗危险)社交赠送者团体。
UNASSIGNED: Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries.
UNASSIGNED: We conducted an open-label, randomized, outpatient, controlled trial in Thailand from October 1, 2021, to June 21, 2022, to assess whether early treatment within 48-h of symptoms onset with combinations of fluvoxamine, bromhexine, cyproheptadine, and niclosamide, given to adults with confirmed mild SARS-CoV-2 infection, can prevent 28-day clinical deterioration compared to standard care. Participants were randomly assigned to receive treatment with fluvoxamine alone, fluvoxamine + bromhexine, fluvoxamine + cyproheptadine, niclosamide + bromhexine, or standard care. The primary outcome measured was clinical deterioration within 9, 14, or 28 days using a 6-point ordinal scale. This trial is registered with ClinicalTrials.gov (NCT05087381).
UNASSIGNED: Among 1900 recruited, a total of 995 participants completed the trial. No participants had clinical deterioration by day 9, 14, or 28 days among those treated with fluvoxamine plus bromhexine (0%), fluvoxamine plus cyproheptadine (0%), or niclosamide plus bromhexine (0%). Nine participants (5.6%) in the fluvoxamine arm had clinical deterioration by day 28, requiring low-flow oxygen. In contrast, most standard care arm participants had clinical deterioration by 9, 14, and 28 days. By day 9, 32.7% (110) of patients in the standard care arm had been hospitalized without requiring supplemental oxygen but needing ongoing medical care. By day 28, this percentage increased to 37.5% (21). Additionally, 20.8% (70) of patients in the standard care arm required low-flow oxygen by day 9, and 12.5% (16) needed non-invasive or mechanical ventilation by day 28. All treated groups significantly differed from the standard care group by days 9, 14, and 28 (p < 0.0001). Also, by day 28, the three 2-drug treatments were significantly better than the fluvoxamine arm (p < 0.0001). No deaths occurred in any study group. Compared to standard care, participants treated with the combination agents had significantly decreased viral loads as early as day 3 of treatment (p < 0.0001), decreased levels of serum cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) as early as day 5 of treatment, and interleukin-8 (IL-8) by day 7 of treatment (p < 0.0001) and lower incidence of post-acute sequelae of COVID-19 (PASC) symptoms (p < 0.0001). 23 serious adverse events occurred in the standard care arm, while only 1 serious adverse event was reported in the fluvoxamine arm, and zero serious adverse events occurred in the other arms.
UNASSIGNED: Early treatment with these combinations among outpatients diagnosed with COVID-19 was associated with lower likelihood of clinical deterioration, and with significant and rapid reduction in the viral load and serum cytokines, and with lower burden of PASC symptoms. When started very soon after symptom onset, these repurposed drugs have high potential to prevent clinical deterioration and death in vaccinated and unvaccinated COVID-19 patients.
UNASSIGNED: Ped Thai Su Phai (Thai Ducks Fighting Danger) social giver group.