Focusing on the Treatment of COVID-19: A Comprehensive Analysis of 226 Trials Registered on Clinicaltrials.gov and ChiCTR

Background: The purpose of this study is to analyze the registered clinical trials of COVID-19, and to provide a reference for the clinical treatment of COVID-19. Methods: Chinese ClinicalTrial Registry (ChiCTR) and Clinicaltrials.gov databases were searched for clinical trials of COVID-19, which were registered from inception to February 29, 2020, to screen out the clinical trials on the treatment of COVID-19, and the research units and regions, sample size, study types, study stages, and intervention measures were analyzed. Results: There were 226 clinical trials on COVID-19 in the 2 databases, and all of them were registered by research units in China. The top ve registered areas were Hubei, Beijing, Shanghai, Guangdong, and Zhejiang. The study type was as follows: interventional study (207, 91.6%) and observational study (18, 8.0%). Clinical trial staging was as follows: exploratory studies/preliminary trials (91, 40.3%), phase I trials (4, 1.8%), phase II trials (12, 5.3%), phase III trials (12, 5.3%), phase IV trials (47, 20.8%), phase I/II trials (2, 0.9%), phase II/III trials (5, 2.2%), and other trials (57, 25.2%). Intervention measures were as follows: there were 143 (63.3%) trials of western medicine treatment, 50 (22.1%) trials of Chinese medicine treatment, and 21 (9.3%) trials of integrated Chinese medicine treatment and western medicine treatment. Conclusion: Researchers have registered a large number of clinical trials in a short time. The number of existing patients of COVID-19 is not enough to support hundreds of clinical trials. There is a lack of multicenter, randomized, double-blind, placebo-controlled trials. placebo-controlled trials. close attention to the results of high-quality clinical and they should translate good results in clinical practice in a timely manner for the treatment of COVID-19.

Chinese medicine treatments for COVID-19 have a good effect 9 . However, the e cacy and safety of these drugs for treating COVID-19 still need to be further con rmed by clinical experiments. Therefore, many clinical Clinical trials for the treatment of COVID-19 that were successfully registered in ChiCTR and Clinicaltrials.gov from inception to February 29, 2020.

Exclusion criteria
Exclusion criteria consisted of: clinical trials whose registration had not been completed as of February 29, 2020; incomplete clinical trials registry; and clinical trials for non-treatment of COVID-19, such as prevention studies, diagnostic studies, and epidemiological studies.

Retrieval strategy
A comprehensive search of ChiCTR and Clinicaltrials.gov was performed for clinical trials on the treatment of COVID-19. The ChiCTR database was searched using the registration title " or or COVID-19" as the project screening criteria. In the Clinicaltrials.gov database, "COVID-19 or 2019-nov or novel coronavirus" was entered in the condition or disease search box to retrieve the information.

Literature selection and data extraction
According to the inclusion and exclusion criteria, two reviewers independently screened trials, extracted contents, and checked with each other. If there was a difference in opinion among them, a third reviewer helped to judge, discuss, and make a decision. If contents were not complete, an attempt was made to contact the registrar to complete the contents. When screening the contents of trials, the title was rst assessed and studies that did not meet the inclusion criteria were excluded. Then the contents of the registered trials were carefully read, and it was decided whether the trials should be included based on the inclusion and exclusion criteria. The extracted contents were as follows: registration number, registered title, registered unit, area, whether or ethical approval was obtained, funding, research type, research phase, research design, interventional measure, sample size, masking, research place, and research time. All of the contents mentioned above were placed into an Excel sheet.

Statistical analysis
Excel (2010 version) was used for statistical analysis, and frequency and composition ratio were mainly used for descriptive statistical analysis.

Discussion
This study was a descriptive evaluation of clinical trials for the treatment of COVID-19, which were registered in Clinicaltrials.gov and ChiCTR. Since the outbreak rst occurred in China, all of the clinical trials for the treatment of COVID 19 were registered by Chinese investigators.
The study found that a large number of clinical trials (246) for COVID-19 were registered in a short time (38 days).
However, an additional 249 clinical trials were registered in Clinicaltrials.gov and ChiCTR, while we were writing this article from March 1, 2020 to March 21, 2020. This is an unprecedented number of trials for a disease in a short time. This indicates that many clinical researchers are trying to identify a safe and effective treatment for COVID-19 during the outbreak of the epidemic.
Besides, it also shows that clinical researchers in China pay more attention to the registration of clinical trials, which is also related to the submission requirement of many well-known journals at home and abroad stating that clinical trials must be registered before publication [12][13][14]  Of the 226 clinical trials, 158 were randomized parallel assignment and only 38 were blind in their design. Most of the trials were not blind in their design. In this way, the results are prone to selective bias; thus, affecting the quality and credibility of the trials. If there is no high-quality research carried out by the design, then it is impossible to provide high-quality clinical research. The results of clinical trials will be questioned. This will also cause a serious waste of research resources.
Some questions have to be considered to use clinical trials to guide the epidemic prevention of COVID-19. First, to avoid wasting resources, researchers should try to conduct multicenter, randomized, double-blind, placebocontrolled trials, to reduce the number of low-quality clinical trials. Second, researchers must conduct clinical trials in strict accordance with the design, or their effort will not yield quali ed results. Third, most of the researchers were medical workers on the front line of COVID 19 treatment, and they did not have enough time to complete clinical trials due to the heavy workload caused by the severe epidemic. It may be a good choice to involve professional research teams to assist them in completing the clinical trials. Fourth, a platform is needed to share and analyze the results of clinical studies so that doctors can get the information immediately and apply the results to the treatment of COVID 19 patients. Fifth, instead of waiting for a paper to be published, researchers should share the results of clinical trials in a timely manner. Sixth, it is necessary to establish a uni ed standard to evaluate the effect of COVID-19 treatment, to compare the effect of different treatment regimens, and explore to a better treatment method.
There are some limitations to this study. This study only analyzed the registered trials in the two databases as of February 29, 2020. After February 29, 2020, many trials were registered, in the process of registration, or had not started registration. Thus, this study could not fully re ect all of the clinical trials of COVID-19. However, this paper analyzed more than 300 registered trials, and the large number was representative to some extent, which could re ect the current clinical trial registration of COVID-19.In addition, some clinical trial registries were incomplete and researchers could not be contacted to supplement the registries, which may lead to biased results.  Other: Hunan4(0), Anhui4(0), Fujian3(2), Heilongjiang3(0), Shanxi2(1), Jilin2(1), Shandong2(0), Guizhou1(0), Liaoning1(0), Neimengu1(1), Hongkong1(0)  Table 3 Overview of the western medicine treatment for COVID-19