Efficacy and safety of Chinese medicine compound for the convalescent COVID-19 patients: Protocol of a multi-centered, randomized, double-blinded, placebo-controlled clinical trial

IF 1.5 Q4 MEDICINE, RESEARCH & EXPERIMENTAL

Contemporary Clinical Trials Communications Pub Date : 2025-12-01 Epub Date: 2025-10-09 DOI:10.1016/j.conctc.2025.101557

Rui Fang , Wanyao Yang , Yue Zhou , Lei Zhao , Le Xie , Jiaxuan Tian , Danhong Liu , Shasha Zhou , Qing Chen , Yanmei Peng , Yunhua Luo , Dahua Wu , Jinwen Ge

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引用次数: 0

Abstract

Background

Convalescent coronavirus disease 2019 (COVID-19) refers to a series of clinical syndromes in patients with COVID-19 infection that follow the relevant discharge indications but do not fulfill the criteria for a clinical cure, and these patients are discharged from the hospital with residual multifunctional deficits, including coughing, fatigue, and insomnia. Due to the prolonged convalescent COVID-19 infection, patients continue to experience symptoms or develop new symptoms after three months of infection, and some symptoms persist for over two months without any apparent triggers, which has a significant impact on the health status and quality of life of the population. Patients with convalescent COVID-19 lack a definitive pharmacological treatment. Traditional Chinese medicine (TCM) exhibits a distinct, synergistic effect on the treatment of convalescent COVID-19. However, there exists a limited number of clinical trials on TCM with lower evidence levels in convalescent COVID-19. Therefore, randomized trials are urgently required.

Methods

A multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial was performed to evaluate the efficacy and safety of Shenlingkangfu (SLKF) granules in treating patients with convalescent COVID-19 and lung-spleen qi deficiency syndrome. Eligible participants were aged 18–75 years, had a confirmed severe acute respiratory syndrome coronavirus 2 infection following a positive result for COVID-19 via polymerase chain reaction (PCR) or rapid antigen test at least six months prior, and satisfied clinical criteria. Individuals with a history of severe pulmonary dysfunction or major liver and kidney illness or those on medications were excluded. Multicenter subjects satisfying all criteria were assigned (1:1) randomly into an intervention group and a control group. After a 2-day adjustment period, a total of 154 participants were randomly divided into an intervention group and a control group. The intervention group was given the SLKF granules orally once a bag, 16.9 g, twice daily, whereas the control group received the SLKF granule simulation at the same dosage. The trial was conducted over 1 month, with assessments performed at baseline and 3 months.

Results

The primary outcomes were the therapeutic efficacy rate and total clinical symptom score. The secondary outcomes included the fatigue self-assessment scale, pain visual analog scale, Pittsburgh sleep quality index, mini-mental state examination, hospital anxiety and depression scale, TCM syndrome score, C-reactive protein, erythrocyte sedimentation rate, and interleukin-6. Three routine examinations, liver and kidney function tests, and electrocardiography were used as safety indicators.

Conclusions

This study aimed to verify whether SLKF granules can significantly improve clinical symptoms, including fatigue, loss of appetite, cough, phlegm, and insomnia, in patients with convalescent COVID-19. For a comprehensive investigation, additional clinical trials with larger sample sizes and longer intervention periods are required.

Clinical Trial Registration Center NCT1900024524, Registered on 26 January 2024.

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复方中药对新冠肺炎恢复期患者的疗效和安全性：多中心、随机、双盲、安慰剂对照临床试验方案

背景2019冠状病毒病恢复期（COVID-19）是指COVID-19感染患者符合相关出院指征，但不符合临床治愈标准，出院时伴有残余的咳嗽、疲劳、失眠等多功能缺陷的一系列临床症状。由于COVID-19感染恢复期较长，患者在感染3个月后持续出现症状或出现新症状，部分症状持续2个月以上，无明显诱因，对人群的健康状况和生活质量产生重大影响。恢复期COVID-19患者缺乏明确的药物治疗。中医药对新冠肺炎恢复期治疗具有明显的协同作用。然而，中药在恢复期COVID-19中的临床试验数量有限，证据水平较低。因此，迫切需要随机试验。方法采用多中心、随机、双盲、安慰剂对照的II期临床试验，评价参灵康复颗粒治疗新冠肺炎恢复期合并肺脾气虚证患者的疗效和安全性。符合条件的参与者年龄在18-75岁之间，在至少6个月前通过聚合酶链反应（PCR）或快速抗原检测结果为COVID-19阳性后确诊为严重急性呼吸综合征冠状病毒2型感染，并满足临床标准。有严重肺功能障碍或严重肝肾疾病史或正在服药的个体被排除在外。满足所有标准的多中心受试者按1:1比例随机分为干预组和对照组。经过2天的调整期，154名参与者随机分为干预组和对照组。干预组给予SLKF颗粒口服1袋，16.9 g，每日2次，对照组给予相同剂量的SLKF颗粒模拟。试验进行了1个多月，在基线和3个月时进行评估。结果主要观察指标为治疗有效率和临床症状总评分。次要指标包括疲劳自评量表、疼痛视觉模拟量表、匹兹堡睡眠质量指数、精神状态量表、医院焦虑抑郁量表、中医证候评分、c反应蛋白、红细胞沉降率、白细胞介素-6。以3项常规检查、肝肾功能检查和心电图作为安全指标。结论本研究旨在验证SLKF颗粒是否能显著改善COVID-19恢复期患者疲劳、食欲不振、咳嗽、痰多、失眠等临床症状。为了进行全面的调查，需要更多样本量更大、干预期更长的临床试验。临床试验注册中心NCT1900024524，注册于2024年1月26日。

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来源期刊

Contemporary Clinical Trials Communications Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

2.70

自引率

6.70%

发文量

146

审稿时长

20 weeks

期刊介绍： Contemporary Clinical Trials Communications is an international peer reviewed open access journal that publishes articles pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from a wide range of disciplines including medicine, life science, pharmaceutical science, biostatistics, epidemiology, computer science, management science, behavioral science, and bioethics. Contemporary Clinical Trials Communications is unique in that it is outside the confines of disease specifications, and it strives to increase the transparency of medical research and reduce publication bias by publishing scientifically valid original research findings irrespective of their perceived importance, significance or impact. Both randomized and non-randomized trials are within the scope of the Journal. Some common topics include trial design rationale and methods, operational methodologies and challenges, and positive and negative trial results. In addition to original research, the Journal also welcomes other types of communications including, but are not limited to, methodology reviews, perspectives and discussions. Through timely dissemination of advances in clinical trials, the goal of Contemporary Clinical Trials Communications is to serve as a platform to enhance the communication and collaboration within the global clinical trials community that ultimately advances this field of research for the benefit of patients.