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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321366

ABSTRACT

Background: Treatment of severe Corona Virus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC‑MSCs) to treat patients with severe COVID-19 with lung damage, based on our phase 1 data.Methods: In this randomised, double-blind, and placebo-controlled trial, we recruited 101 eligible patients with severe COVID-19 with lung damage aged between 18–74 years from two hospitals. Enrolled patients were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. We excluded patients with malignant tumours, shock, or other organ failure. The primary endpoint was an altered proportion of whole lung lesion areas from baseline to day 28, measured by chest computed tomography. Other imaging outcomes, 6-minute walk test, maximum vital capacity, diffusing capacity, plasma biomarkers, and adverse events were recorded and analysed. Primary analysis was done in the modified intention-to-treat (mITT) population and safety analysis was done in all patients who started their assigned treatment. Findings: From March 5, 2020, to March 28, 2020, 100 patients were finally enrolled and received either UC-MSCs (n = 65) or placebo (n = 35). During follow-up, the patients receiving UC-MSCs exhibited a trend of numerical improvement in whole lung lesions from baseline to day 28 compared with the placebo cases. UC-MSCs administration significantly reduced the proportions of consolidation lesions from baseline to day 28 in the treated patients compared with the placebo subjects. The 6-minute walk test showed an increased distance in patients treated with UC-MSCs. Notably, UC-MSCs delivery was well tolerated, with no serious adverse events.Interpretation: UC-MSCs treatment is a safe and potentially effective therapeutic approach for patients with severe COVID‑19. The trial suggests that UC-MSCs administration might benefit patients with COVID-19 with lung damage at the convalescent stage as well as the progression stage.Trial Registration: This trial is registered with ClinicalTrials.gov, number NCT04288102.Funding Statement: This trial was supported by The National Key R&D Program of China (2020YFC0841900, 2020YFC0844000, 2020YFC08860900);The Innovation Groups of the National Natural Science Foundation of China (81721002);The National Science and Technology Major Project (2017YFA0105703).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: Ethical approval was obtained from the institutional review boards of each participating hospital. Written informed consent was obtained from all the enrolled patients or their legal representatives if they were unable to provide consent.

2.
Signal Transduct Target Ther ; 6(1): 58, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-1078577

ABSTRACT

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.


Subject(s)
COVID-19/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , SARS-CoV-2 , Umbilical Cord , Aged , Allografts , COVID-19/mortality , COVID-19/physiopathology , Double-Blind Method , Female , Humans , Male , Middle Aged , Treatment Outcome
3.
Drug Des Devel Ther ; 14: 5097-5108, 2020.
Article in English | MEDLINE | ID: covidwho-948000

ABSTRACT

OBJECTIVE: This study aims to comprehensively evaluate the characteristics of clinical drug trials to facilitate the collection of evidence for COVID-19 drug treatments. METHODS: A retrospective analysis of 910 trials retrieved on August 7, 2020. RESULTS: A total of 910 registered clinical trials with at least one drug intervention were evaluated. The number of registrations (32.4%, 295) from the United States accounted for nearly one-third of the total and far exceeded that of other countries individually. Furthermore, the peak number of trials were registered in April (34.3%, 312). Over half of the trials (51.2%, 466) are in the recruitment phase, and only 4.2% (38) of the trials have been completed. The median (interquartile range) estimated enrollment is 127 (59, 365). In 39% (355) of trials, the estimated enrollment is less than 100 participants. A total of 94.5% (790) of the trials use randomization in the allocation, 82.7% (753) use a parallel intervention mode, and 52.2% (475) use masking. A total of 287 drug names have been standardized and mapped. "Hydroxychloroquine" is the leading drug among the registered trials (7.47%, 68). Among the main countries contributing to investigations on "hydroxychloroquine", the United States ranks first with 36.76% (25) of the trials. CONCLUSION: The designs of COVID-19 clinical drug trials have greatly improved in terms of the implementation of randomization and, particularly, blinding methods. In terms of drug reuse, the number of drug types has greatly increased, and hundreds of drugs have been used for efficacy screening. The emergence of large-sample registration trials is expected to address the uncertainty regarding the current clinical efficacy of some drugs.


Subject(s)
COVID-19/drug therapy , Clinical Trials as Topic/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Child , Child, Preschool , Drug Repositioning , Female , Humans , Hydroxychloroquine/therapeutic use , Infant , Male , Middle Aged , Pandemics , Research Design , Young Adult
4.
Curr Med Res Opin ; 36(7): 1131-1135, 2020 07.
Article in English | MEDLINE | ID: covidwho-305917

ABSTRACT

Objective: The aim of this study was to provide recommendations for improving the design of subsequent studies through analysis of the registered coronavirus disease 2019 (COVID-19) clinical trials.Methods: A retrospective analysis of 189 trial retrievals achieved on 20 February 2020.Results: A total of 189 trials are included in the study. There were 69.3% interventional studies, 21.7% observational studies, 5.3% diagnostic tests and 3.7% other studies. The following statistics are provided only for the interventional studies. Severity of disease: 5.3% light and common type, 17.6% severe and critically ill and 59.6% with no restricted classification. Medication use: 51.1% Western medicine, 32.1% Chinese medicine, 10.7% blood related product and 6.1% non-drug therapy. The median and inner quantile range of the sample sizes included in these studies: 104 (IQR: 60, 200). Primary outcome type most used: 45.8% with clinical characteristics and 21.4% with virological. Study design characteristics: 71% of all studies were randomized, 5% of all studies were blinded, 18% of all studies were multicenter and 76% of all studies were single center.Conclusion: Although many COVID-19 studies include randomization in their design, the lack of additional double-blind and placebo-controlled elements in their designs result in a less robust evaluation of intervention safety and efficacy. Furthermore, similar or repeated research and small sample studies that have less promise in gains of new information have possibly led to a shortage of recruitable patients and become a barrier to the completion of large multicenter clinical trial studies.


Subject(s)
Betacoronavirus , Clinical Trials as Topic/organization & administration , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Research Design , COVID-19 , Humans , Pandemics , SARS-CoV-2
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