An evidence mapping and analysis of registered COVID-19 clinical trials in China

Abstract

Background: This article aims to summarize the key characteristics of registered trials of 2019 novel coronavirus (COVID-19), in terms of their spatial and temporal distributions, types of design and interventions, and patient characteristics among others.

Methods: A comprehensive search of the registered COVID-19 trials has been performed on platforms including ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (WHO ICTRP), Chinese Clinical Trials Registry (CHiCTR), Australian Clinical Trials Registry, Britain's National Research Register (BNRR), Current Control Trials (CCT), and Glaxo Smith Kline Register. Trials registered at the first 8 weeks of the COVID-19 outbreak are included, without language restrictions. For each study, the registration information, study design, and administrator information are collected and summarized.

Results: A total of 220 registered trials were evaluated as of February 27, 2020. Hospital-initiated trials were the majority and account for 80% of the sample. Among the trials, pilot studies and phase 4 trials are more common and represent 35% and 19.1% of the sample, respectively. The median sample size of the registered trials is 100, with interquartile range 60-240. Further, 45.9% of the trials mentioned information on a data monitoring committee. 54.5% of the trials did not specify the disease severity among patients they intend to recruit. Four types of interventions are most common in the experimental groups across the registered studies: antiviral drugs, Traditional Chinese Medicine (TCM), biological agents, and hormone drugs. Among them, the TCM and biological agents are frequently used in pilot study and correspond to a variety of primary endpoints. In contrast, trials with antiviral drugs have more targeted primary outcomes such as "COVID-19 nucleic acid test" and "28-day mortality."

Conclusions: We provide an evidence mapping and analysis of registered COVID-19 clinical trials in China. In particular, it is critical for ongoing and future studies to refine their research hypothesis and better identify their intervention therapies and the corresponding primary outcomes. It is also imperative for multiple public health divisions and research institutions to work together for integrative clinical data capture and sharing, with a common objective of improving future studies that evaluate COVID-19 interventions.

Fig. 1

Number of new trials registered in trial registry platforms each week and by initiators. The number of new registrations per week (beginning on the date indicated) from January 23, 2020, to February 27, 2020. The “Industry” category includes all commercial data providers; the “University” category includes university and college data providers. The “combined” category combines the numbers of registrations in “Hospital,” “University,” and “Industry” categories

Fig. 2

Number of registered trials distributed in each area

Fig. 3

A multidimensional plot for the relationship between test drugs, outcomes, and disease severity. Each circle or triangle represents one type of intervention specified in the corresponding row. (1) Circle and triangle size: number of studies evaluating each intervention (larger = more studies). (2) Circle color: stage of disease (green for mild, blue for moderate, red for severe). Biological agents: interferon alfa, thymosin, vMIP, stem cell-based medicinal products, novaferon, plasma therapy, tocilizumab, camrelizumab, and immunoglobulin. Antiviral drugs: Arbidol tablets, chloroquine phosphate tablets, ritonavir, lopinavir, hydroxychloroquine, chloroquine, baloxavir marboxil, emtricitabine, polyinosinic-polycytidylic acid injection, favipiravir, oseltamivir, remdesivir, darunavir, cobicistat, and ribavirin. Hormone drugs: methylprednisolone. TCM: clearing lung formula (Qing Fei Fang), ginseng, poria and Atractylodes macrocephalae powder (Shēn Líng Bái Zhú Săn), instant relief for cough syrup (Ke Su Ting Tang Jiang), Chinese medicine formulas 1 and 2 (Zhong Yao 1 Hao and 2 Hao), cough cleared capsules (Ke Qing Capsules), clearing both common cold and cough capsules (Gan Ke Shuang Qing Capsules), antiviral oral liquid, the Radix Fici Hirtae preventing COVID-19 formula (WuZhi Fang Guan Fang) antiviral particles, YinHu QingWen decoction, relief for heat and toxin injection (Re Du Ning Zhu She Ji), relief for inflammation injection (Xi Yan Ping Injection), ginseng and Radix Astragali reinforcing health injection (Shen Qi Fu Zheng Injection), and others not provided