Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland.
Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland.
Int J Mol Sci. 2023 Sep 18;24(18):14247. doi: 10.3390/ijms241814247.
In March 2020, the World Health Organization (WHO) announced a global pandemic of coronavirus disease 2019 (COVID-19) that presented mainly as an acute infection of the lower respiratory tract (pneumonia), with multiple long-term consequences, including lung fibrosis. The aim of this study was to evaluate the influence of potassium canrenoate on inflammatory markers in the treatment of COVID-19 pneumonia. A randomized clinical trial (RCT) of intravenous potassium canrenoate vs. placebo was performed between December 2020 and November 2021. This study is a secondary analysis of that RCT. In the final analysis, a total of 49 hospitalized patients were included (24 allocated to the potassium canrenoate group and 25 to the placebo group). Patients were assessed by serum testing and blood cell cytometry on day 1 and day 7 of the intervention. Age, sex, and body mass index were not significantly different between the placebo group and intervention group. Although there was a significantly higher rate of ischemic heart disease in the placebo group, rates of other preexisting comorbidities were not significantly different. There were no significant differences in the inflammatory parameters between the potassium canrenoate and placebo groups on day 1 and day 7. However, the intragroup comparisons using Wilcoxon's test showed significant differences between day 1 and day 7. The CD3% for potassium canrenoate increased significantly between day 1 and day 7 (12.85 ± 9.46; 11.55 vs. 20.50 ± 14.40; 17.80; = 0.022), while the change in the placebo group was not significant (15.66 ± 11.39; 12.65 vs. 21.16 ± 15.37; 16.40; = 0.181). The IL-1ß total count [%] increased over time for both potassium canrenoate (0.68 ± 0.58; 0.45 vs. 1.27 ± 0.83; 1.20; = 0.004) and placebo (0.61 ± 0.59; 0.40 vs. 1.16 ± 0.91; 1.00; = 0.016). The TNF-α total count (%) decreased significantly between day 1 and day 7 for potassium canrenoate (0.54 ± 0.45; 0.40 vs. 0.25 ± 0.23; 0.10; = 0.031), but not for placebo (0.53 ± 0.47; 0.35 vs. 0.26 ± 0.31; 0.20; = 0.056). Interleukin-6 (pg/mL) showed a significant decrease between day 1 and day 7 for potassium canrenoate (64.97 ± 72.52; 41.00 vs. 24.20 ± 69.38; 5.30; = 0.006), but not the placebo group. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19-induced pneumonia may be associated with significant changes in certain inflammatory markers (interleukin-6, CD3%, TNF-α), potentially related to pulmonary fibrosis. Although some positive trends were observed in the potassium canrenoate group, none of these observations reached statistical significance. Any possible benefits from the use of potassium canrenoate as an anti-inflammatory or antifibrotic drug in COVID-19 patients require further investigation.
2020 年 3 月，世界卫生组织（WHO）宣布了一场由冠状病毒病 2019（COVID-19）引起的全球大流行，其主要表现为下呼吸道（肺炎）的急性感染，并伴有多种长期后果，包括肺纤维化。本研究旨在评估坎地沙坦钾对 COVID-19 肺炎治疗中炎症标志物的影响。我们进行了一项静脉注射坎地沙坦钾与安慰剂的随机临床试验（RCT），时间为 2020 年 12 月至 2021 年 11 月。本研究是该 RCT 的二次分析。在最终分析中，共有 49 名住院患者入组（24 名分配到坎地沙坦钾组，25 名分配到安慰剂组）。患者在干预的第 1 天和第 7 天通过血清检测和血液细胞计数进行评估。安慰剂组和干预组之间的年龄、性别和体重指数无显著差异。尽管安慰剂组的缺血性心脏病发病率较高，但其他既往合并症的发病率无显著差异。坎地沙坦钾组和安慰剂组在第 1 天和第 7 天的炎症参数无显著差异。然而，使用 Wilcoxon 检验的组内比较显示第 1 天和第 7 天之间存在显著差异。坎地沙坦钾的 CD3%在第 1 天至第 7 天之间显著增加（12.85 ± 9.46；11.55 与 20.50 ± 14.40；17.80； = 0.022），而安慰剂组的变化不显著（15.66 ± 11.39；12.65 与 21.16 ± 15.37；16.40； = 0.181）。白细胞介素-1ß总计数[%]在坎地沙坦钾组和安慰剂组均随时间增加（0.68 ± 0.58；0.45 与 1.27 ± 0.83；1.20； = 0.004 和 0.61 ± 0.59；0.40 与 1.16 ± 0.91；1.00； = 0.016）。坎地沙坦钾组的肿瘤坏死因子-α总计数（%）在第 1 天至第 7 天之间显著下降（0.54 ± 0.45；0.40 与 0.25 ± 0.23；0.10； = 0.031），但安慰剂组无显著下降（0.53 ± 0.47；0.35 与 0.26 ± 0.31；0.20； = 0.056）。白细胞介素-6（pg/mL）在坎地沙坦钾组中从第 1 天到第 7 天显著下降（64.97 ± 72.52；41.00 与 24.20 ± 69.38；5.30； = 0.006），但安慰剂组无显著下降。本 RCT 表明，COVID-19 诱导性肺炎患者给予坎地沙坦钾可能与某些炎症标志物（白细胞介素-6、CD3%、肿瘤坏死因子-α）的显著变化相关，这些变化可能与肺纤维化有关。尽管坎地沙坦钾组观察到一些阳性趋势，但这些观察结果均未达到统计学意义。坎地沙坦钾作为 COVID-19 患者的抗炎或抗纤维化药物可能带来的任何益处，仍需进一步研究。
