Siddha Central Research Institute, Chennai, India.
ICMR-National Institute of Epidemiology, Chennai, India.
Trials. 2020 Oct 27;21(1):892. doi: 10.1186/s13063-020-04823-z.
The primary objectives of this study are to determine efficacy of Siddha medicine, Kabasura kudineer in reduction of SARS-CoV-2 viral load and reducing the onset of symptoms in asymptomatic COVID-19 when compared to Vitamin C and Zinc (CZ) supplementation. In addition, the trial will examine the changes in the immunological markers of the Siddha medicine against control. The secondary objectives of the trial are to evaluate the safety of the Siddha medicine and to document clinical profile of asymptomatic COVID-19 as per principles of Siddha system of Medicine.
A single centre, open-label, parallel group (1:1 allocation ratio), exploratory randomized controlled trial.
Cases admitted at non-hospital settings designated as COVID Care Centre and managed by the State Government Stanley Medical College, Chennai, Tamil Nadu, India will be recruited. Eligible participants will be those tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain reaction (RT-PCR) aged 18 to 55 years without any symptoms and co-morbidities like diabetes mellitus, hypertension and bronchial asthma. Those pregnant or lactating, with severe respiratory disease, already participating in COVID trials and with severe illness like malignancy will be excluded.
Adopting traditional methods, decoction of Kabasura kudineer will be prepared by boiling 5g of KSK powder in 240 ml water and reduced to one-fourth (60ml) and filtered. The KSK group will receive a dose of 60ml decoction, orally in the morning and evening after food for 14 days. The control group will receive Vitamin C (60000 IU) and Zinc tablets (100mg) orally in the morning and evening respectively for 14 days.
The primary outcomes are the reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR] from the baseline to that of seventh day of the treatment, prevention of progression of asymptomatic to symptomatic state (clinical symptoms like fever, cough and breathlessness) and changes in the immunity markers [Interleukins (IL) 6, IL10, IL2, Interferon gamma (IFNγ) and Tumor Necrosis Factor (TNF) alpha]. Clinical assessment of COVID-19 as per standard Siddha system of medicine principles and the occurrence of adverse effects will be documented as secondary outcomes.
The assignment to the study or control group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and informed consent procedures.
BLINDING (MASKING): This study is unblinded. The investigators will be blinded to data analysis, which will be carried out by a statistician who is not involved in the trial.
NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size could not be calculated, as there is no prior trial on KSK. This trial will be a pilot trial. Hence, we intend to recruit 60 participants in total using a 1:1 allocation ratio, with 30 participants randomised into each arm.
Protocol version 2.0 dated 16 May 2020. Recruitment is completed. The trial started recruitment on the 25 May 2020. We anticipate study including data analysis will finish on November 2020. We also stated that protocol was submitted before the end of data collection TRIAL REGISTRATION: The study protocol was registered with clinical trial registry of India (CTRI) with CTRI/2020/05/025215 on 16 May 2020.
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).
本研究的主要目的是确定 Siddha 医学药物 Kabasura kudineer 在降低 SARS-CoV-2 病毒载量和减少无症状 COVID-19 出现症状方面的疗效，与维生素 C 和锌（CZ）补充剂相比。此外，该试验将检查 Siddha 药物对对照的免疫标记物的变化。该试验的次要目的是评估 Siddha 药物的安全性，并根据 Siddha 医学系统的原则记录无症状 COVID-19 的临床特征。
一项单中心、开放标签、平行组（1:1 分配比例）、探索性随机对照试验。
将招募在印度钦奈泰米尔纳德邦斯坦利医学院指定的非医院环境中收治的 COVID 护理中心的病例。合格的参与者将是通过逆转录酶聚合酶链反应（RT-PCR）检测到 COVID-19 呈阳性的 18 至 55 岁的无症状和无合并症（如糖尿病、高血压和支气管哮喘）的人。那些孕妇或哺乳期妇女、患有严重呼吸道疾病、已经参加 COVID 试验和患有严重疾病如恶性肿瘤的人将被排除在外。
采用传统方法，将 Kabasura kudineer 煎剂煮沸 5g KSK 粉末在 240ml 水中，减少至四分之一（60ml）并过滤。KSK 组将每天早上和晚上在饭后口服 60ml 煎剂，连续服用 14 天。对照组将每天早上和晚上分别口服维生素 C（60000IU）和锌片（100mg），连续服用 14 天。
主要结果是从基线到治疗第 7 天 SARS-CoV-2 载量的降低[以 RT-PCR 的循环阈值（CT）值衡量]，预防无症状向有症状状态的进展（如发热、咳嗽和呼吸急促等临床症状）以及免疫标志物[白细胞介素（IL）6、IL10、IL2、干扰素γ（IFNγ）和肿瘤坏死因子（TNF）α]的变化。根据标准 Siddha 医学原则对 COVID-19 进行临床评估和记录不良事件的发生情况作为次要结果。
通过在 Microsoft Excel 中使用随机数生成器进行随机化，将研究或对照组的分配数量平均分配，该随机数生成器由不参与试验的统计学家生成。分配方案将由独立的统计学家使用密封信封制作。在符合入选标准并获得知情同意后，立即对参与者进行分组。
盲法（掩蔽）：本研究为非盲法。研究者对数据分析进行盲法，数据分析将由不参与试验的统计学家进行。
随机化的数量（样本量）：由于没有关于 KSK 的先前试验，因此无法计算样本量。本试验将是一项初步试验。因此，我们计划总共招募 60 名参与者，采用 1:1 分配比例，每组 30 名参与者。
协议版本 2.0 日期为 2020 年 5 月 16 日。招募工作已经完成。试验于 2020 年 5 月 25 日开始招募。我们预计包括数据分析在内的研究将于 2020 年 11 月完成。我们还表示，协议在数据收集结束前提交给了印度临床试验注册中心（CTRI），注册号为 CTRI/2020/05/025215。
完整协议作为附加文件附加于此，可从试验网站访问（附加文件 1）。为了加快传播这一材料的速度，熟悉的格式已被删除；本信函是该完整协议的主要内容摘要。该研究方案已按照标准方案项目：推荐临床干预试验（SPIRIT）指南（附加文件 2）进行报告。
