Blum Vinicius Fontanesi, Cimerman Sérgio, Hunter James R, Tierno Paulo, Lacerda Acioly, Soeiro Alexandre, Cardoso Florentino, Bellei Nancy Cristina, Maricato Juliana, Mantovani Nathalia, Vassao Marcella, Dias Danilo, Galinskas Juliana, Janini Luis Mário Ramos, Santos-Oliveira Joanna Reis, Da-Cruz Alda Maria, Diaz Ricardo Sobhie
Federal University of São Paulo, São Paulo, Brazil.
Instituto de Infectologia Emilio Ribas, São Paulo, Brazil.
EClinicalMedicine. 2021 Jul;37:100981. doi: 10.1016/j.eclinm.2021.100981. Epub 2021 Jun 27.
The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates' drugs. Nitazoxanide (NTZ) has a broad antiviral effect.
This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20, 2020, to September 21, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used.
Two patients died in the NTZ arm compared to 6 in the placebo arm ( = 0.564). NTZ was superior to placebo when considering SSD ( < 0001), the mean time for hospital discharge (6.6 vs. 14 days, = 0.021), and negative PCR at day 21 ( = 0.035), whereas the placebo group presented more adverse events ( = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo ( = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group ( = 0.04). A decrease from baseline was higher in the NTZ group for d-Dimer ( = 0.001), US-RCP ( < 0.002), TNF ( < 0.038), IL-6 ( < 0.001), IL-8 ( = 0.014), HLA DR. on CD4 lymphocytes ( < 0.05), CD38 in CD4 and CD8 (both < 0.05), and CD38 and HLA-DR. on CD4+ ( < 0.01).
Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.
缺乏治疗新型冠状病毒肺炎（COVID-19）的特异性抗病毒药物，促使人们重新考虑其他候选药物。硝唑尼特（NTZ）具有广泛的抗病毒作用。
这是一项随机、双盲的试点临床试验，在2020年5月20日至2020年9月21日期间，对50例新型冠状病毒逆转录聚合酶链反应（SARS-COV-2 RT-PCR）呈阳性（PCR+）且因轻度呼吸功能不全住院的患者（每组25例），比较每日两次服用600毫克NTZ与安慰剂，疗程为7天（ClinicalTrials.gov标识符：NCT04348409）。评估了临床和病毒学终点以及炎症生物标志物。采用了疾病严重程度五分制（SSD）。
NTZ组有2例患者死亡，而安慰剂组有6例（P = 0.564）。在考虑SSD（P < 0.001）、平均出院时间（6.6天对14天，P = 0.021）和第21天PCR转阴情况（P = 0.035）时，NTZ优于安慰剂，而安慰剂组出现了更多不良事件（P = 0.04）。在可能与研究药物相关的不良事件中，NTZ组检测到14例，安慰剂组检测到22例（P = 0.24）。在30例不太可能相关的不良事件中，21例发生在安慰剂组（P = 0.04）。NTZ组中，D-二聚体（P = 0.001）、超敏C反应蛋白（hs-CRP）（P < 0.002）、肿瘤坏死因子（TNF）（P < 0.038）、白细胞介素-6（IL-6）（P < 0.001）、白细胞介素-8（IL-8）（P = 0.014）、CD4+淋巴细胞上的人类白细胞抗原DR（HLA-DR）（P < 0.05）、CD4+和CD8+细胞上的CD38（两者P < 0.05）以及CD4+细胞上的CD38和HLA-DR（P < 0.01）较基线水平下降更为明显。
与安慰剂相比，NTZ在临床和病毒学结局以及炎症结局改善方面具有优势，这使得该药物在更大规模的临床试验中用于中度COVID-19患者的进一步研究具有必要性。安慰剂组不良事件发生率较高可能归因于与COVID-19相关的症状。
