Novel coronavirus pneumonia: what are the 24 clinical trials in 116 days?

Wang Shiwei Novel coronavirus attacked Wuhan city in January 23, 2020 All personnel and vehicles will be suspended from the upper reaches of the Yangtze River Since then, a number of provinces and cities have launched level I public health emergency response According to the official website of the Chinese clinical trial registry (ChiCTR), there are 116 clinical trials in progress from January 23 to February 15, involving more than 50 medical institutions in and outside Hubei Province These clinical trials involve both western medicine and traditional Chinese medicine For example, in the aspect of Western medicine, there are the old antimalarial drug chloroquine, the influenza drug abidol, and the anti AI drug ritonavir In traditional Chinese medicine, there are Shuanghuanglian oral liquid, Tanreqing injection, Reduning injection, Jinyinhua decoction, and Taijiquan assisted rehabilitation In cell therapy, there are cord blood stem cells, uterine blood stem cells and cord blood NK cells Which drugs and treatments will become the means of treatment Which will be eliminated due to ineffectiveness What could be controversial? This paper attempts to analyze these data in the form of charts Behind the data, there may be the turning point of the epidemic that we have been waiting for a long time From the pull-out clinical trial start-up time line, we can clearly see that since February, the start-up speed of clinical trials in major medical institutions has been significantly faster than that in January As of February 15, at least two clinical trials have been registered every day in February In the last working day, the number of clinical trials registered reached a peak of 18 Of the 116 clinical trials, 38 were conducted by researchers in medical institutions in Hubei Province, while the remaining 78 were led by medical institutions in 24 provinces including Guangdong Province, Zhejiang Province and Sichuan Province Novel coronavirus pneumonia related clinical trials are the most common among the provinces except Guangdong, Hubei province (19), Zhejiang (16), Sichuan (11), Beijing (7) and Chongqing (7) If we further refine the analysis perspective to the specific units carrying out clinical trials, we can find that Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology, the First Affiliated Hospital of Zhejiang University Medical College and Huaxi Hospital of Sichuan university rank the top three clinical trials in terms of 8, 7 and 5, respectively In the past 24 days, more than seven clinical trials registered nationwide have become intervention studies Novel coronavirus pneumonia (COVID-19) novel coronavirus pneumonia (COVID-19) epidemic prevention and control program for community residents, and evaluation of immune Library (TCR&BCR) and immunotherapy in peripheral blood of patients with pneumonia of new coronavirus (COVID-19) in Zhejiang University First Affiliated Hospital of Zhejiang University were studied The official website of ChiCTR defines the intervention study and observation study corresponding to the clinical trial Among them, the intervention clinical trial refers to any study with randomized control design in any treatment study, in which the subjects or subjects are randomly assigned to receive one or more kinds of medical interventions (such as preventive health care, drugs, surgical treatment, behavior therapy, etc.) in advance to evaluate the impact of medical measures on health outcomes, including pre-trial, formal trial, pre market or market launch Post drug or medical device clinical trial; observational study refers to the non randomized control design trial in treatment study, including single case study, continuous case study, cohort study or non randomized control study According to who regulations, samples from or on human body, including tissues, blood, body fluids, hair, cells, etc., including etiology research, prognosis research, diagnostic test, epidemiological research, etc., shall be registered no matter what design scheme is adopted In addition, of the 116 clinical trials, 70 were western medicine, 40 were traditional Chinese medicine, and 6 were cell therapy According to the type of drug use scheme, except 9 clinical trials, all of them were used alone Due to the limited space, this paper does not list 70 clinical trials of Western medicine Among all the 9 clinical trials, the frequency of lopinavir / ritonavir was the highest, which was involved in 6 clinical trials The subjects of the combination included interferon - α 2B, FTC / TAF, thymosin A1, recombinant cytokine gene-derived protein injection, chloroquine and abidol Lopinavir is an antiretroviral drug of protease inhibitors Abbott has developed a compound preparation of lopinavir and another protease inhibitor ritonavir, which consists of one unit dose of lopinavir and one quarter of the dose of ritonavir The preparation was approved by FDA to be listed in the United States in 2000, and approved to be listed in China in 2007 The product is called kaletra, which is mainly used in the clinical treatment of AIDS In the novel coronavirus pneumonia treatment plan (Trial), which is written by the National Health Council for the new crown epidemic organization fifth edition, the "antiviral treatment" part refers to the possibility of using R-P or ritonavir However, according to the report of the research team of the fifth hospital of Sun Yat sen University, the early use of lopinavir / ritonavir showed little effect, and the negative conversion rate of pharyngeal swab nucleic acid within 5 days was only 20% (3 / 15) We have noticed that novel coronavirus pneumonia has been mentioned in many attempts to fight against new crown pneumonia The concepts of traditional Chinese medicine involved include Tanreqing, Lianhuaqingwen capsule, lung rehabilitation, Taijiquan, gubiaodiuling, Reduning injection, Shuanghuanglian oral liquid, Jinyebaidu granules, Xiyanping, babaodan, etc the application fields include light and severe treatment, rehabilitation, psychological intervention, prevention and epidemiological research On the morning of February 15, Wang Hesheng, deputy director of the National Health Commission and member of the Standing Committee of the Hubei provincial Party committee, introduced at a press conference held by the State Council's new office that at present three national medical teams of traditional Chinese medicine have been sent out, and the national system of traditional Chinese medicine has been organized to send medical team members to Hubei More than half of the confirmed cases in Hubei Province have been treated with traditional Chinese medicine Wang Hesheng pointed out that "through coordinating the resources of Chinese and Western medicine, cooperating in tackling key problems and complementing each other's advantages, we strive to improve the cure rate, reduce the mortality rate to the greatest extent, and practically safeguard the life safety and health of the people." This also gives official recognition to the application of traditional Chinese medicine in the fight against the epidemic Among all the medical institutions carrying out clinical trials related to traditional Chinese medicine, Xinhua Hospital Affiliated to Hubei University of traditional Chinese medicine / Hubei integrated hospital of traditional Chinese and Western Medicine carried out four clinical trials involving the concept of traditional Chinese medicine, which is the medical institution with the largest number of such clinical trials in the registry Among them, Xinhua Hospital Affiliated to Hubei University of traditional Chinese medicine / Hubei integrated hospital of traditional Chinese and Western medicine awarded lung rehabilitation and Taijiquan for rehabilitation of patients with new crown in two experiments According to the official website of ChiCTR searched by arterial network, the two clinical trials registered on February 2 are planned to be 50 patients in the experimental group and 50 patients in the control group However, as of publication, the above clinical trials have not yet started to recruit research subjects At the same time, we noted that the above two clinical trials were approved by the ethics committee of Hubei integrated traditional Chinese and Western medicine hospital, but the attachment of the approval document of the ethics committee could not be downloaded In fact, novel coronavirus pneumonia is in the outbreak stage, and clinical trials do face special challenges For example, in the current relatively disordered state, clinical trials are faced with the problems of establishing the infrastructure needed for clinical trials, training researchers and obtaining sufficient cases Zhai Xiaomei, executive director and distinguished professor of bioethics research center of Chinese Academy of Medical Sciences / Peking Union Medical College, said in an interview earlier that the research team conducting clinical trials at this stage is more important to balance the urgent needs of patients' treatment and research needs In addition, novel coronavirus pneumonia treatment regimens based on cell therapy have been registered in clinical trials, involving stem cells, nuclear cells, NK cells and so on 6 new methods of cell therapy are also being noted Among them, there are 3 clinical trials involving mesenchymal stem cells in total Xiangyang No.1 People's Hospital, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology and Guangzhou rapamycin company took the lead in carrying out the above clinical trials Mesenchymal stem cells (MSCs) are important members of stem cell family They come from mesoderm in early development and belong to pluripotent stem cells MSCs can be differentiated into fat, bone, cartilage, muscle, tendon, ligament, nerve, liver, heart muscle, endothelium and other tissue cells under specific induction conditions in vivo or in vitro After continuous subculture and cryopreservation, MSCs still have multi-directional differentiation potential, which can be used as ideal seed cells for the repair of tissue and organ damage caused by aging and pathological changes In 2012, osirs declared that MSC was listed as a drug and was approved by the Canadian FDA, which is also the first drug approval document of MSCs in the world In recent years, there have been 5 new drug applications of mesenchymal stem cell technology in China, which have entered clinical trials by implication However, after the arterial network talked with the stem cell industry practitioners and investors, it is believed that at present, the research and development of new stem cell drugs are still at the forefront of low maturity technology in the world, and the process of their industrialization still has a long way to go For clinical trials of cell therapy registered by ChiCTR, especially those involving stem cell technology, we will continue to pay attention to its subsequent data release In general, patients who have survived bacterial or viral infection have developed humoral immunity to specific pathogens The blood usually contains high titer of specific antibodies, while transfusion of convalescent blood products (CBP) As a result, the patients can obtain passive immunity, neutralize specific pathogens, and finally eliminate pathogens in the blood circulation Passive immunity is a kind of artificial immunity based on the principle of plasma therapy In February 13th, novel coronavirus pneumonia was recovered by Zhang Dingyu, President of Wuhan golden Yin Tan Hospital, in a news conference China's novel coronavirus pneumonia (COVID-19) study was completed by the Institute of transfusion medicine of the Chinese Academy of Medical Sciences in February 12th We searched the official website of ChiCTR According to the plan, the clinical trial will be included in the participants from February 14 According to reports, the clinical trial used a multicenter, randomized, parallel controlled trial design 150 subjects were enrolled in the treatment group and the control group respectively, and the experiment was completed in the Affiliated Union Hospital of Tongji Medical College of Huazhong University of science and technology, Wuhan Red Cross Hospital of Hubei Province and Wuhan blood center According to the experimental design, in addition to routine antiviral therapy, the patients in the treatment group who have achieved severe infection should be injected with convalescent plasma whose antibody titer is higher than 1:80 If the patients meet the entry criteria, once they enter the group, they should be infused as soon as possible At the beginning and end of each infusion, the date and time of plasma infusion should be recorded (24-hour system); the patients in the control group should use the routine antiviral therapy