Compilation of registered clinical trials for the treatment of COVID-19 infection

The Wuhan city, the capital of Hubei province in China became the focal point for origin of virulent disease which later named as COVID-19. This paper aims to analyze the on-going clinical trials for drugs/interventions used for treatment of COVID-19 infection in open domain. The data on ongoing clinical trials on COVID-19 was retrieved from database clinicaltrials.gov. The data extracted includes national clinical trial registry number, title of study, recruitment status, results availability, intervention, outcome measure, sponsorship, study types, study design, start and completion dates, and location. All the extracted data was analyzed. As on 10th August 2020, a total of 2935 trials were registered in different countries. Of which 1115 trials are being conducted in Europe and 640 in United States of America (USA). Majority of COVID-19 clinical trials (95%) were enrolling all age groups including children and older adults. Similarly, majority of trials were including both genders (97%). Among all these clinical trials ongoing on COVID-19, 1645 were interventional, 1266 were observational studies. In interventional study 876 trials used drug intervention. Among all these trials 390 different drug interventions are being tried. Among these hydroxychloroquine, antiretrovirals and angiotensin converting enzyme (ACE) inhibitors were top three drug groups. The conduct of clinical trials in time of pandemic have so many tenacious issues that need to be addressed. It is very important to utilize the resources efficiently such as following a standard protocol then one can easily pool the data of various trials conducted at various places. Given the smaller sample sizes, long completion period, high risk of bias and imprecise information, it will take quite a long time to obtain high quality clinical evidence for the treatment of COVID-19 infection.

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Chinese Clinical Studies for Pharmacological Treatments of Coronavirus Disease 2019 (COVID-19)

10.20944/preprints202004.0279.v1 ◽

2020 ◽

Author(s):

Ru Han ◽

Yitong Wang ◽

Monique Dabbous ◽

Shuyao Liang ◽

Tingting Qiu ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Clinical Studies ◽

Observational Studies ◽

Reference Group ◽

Descriptive Analysis ◽

Secondary Analysis ◽

Trial Registry ◽

Primary Analysis ◽

Clinical Trial Registry

Objectives: This study aims to identify, report, and analyze registered and published clinical trials and observational studies for the pharmacological treatment of COVID-19 conducted in China. Methods: A strategic search was conducted via the Chinese Clinical Trial Registry to identify and extract clinical trials and observational studies registered and conducted in China for the pharmacological treatment of COVID-2019 between January 1st, 2020 and March 21st, 2020. This was further supplemented by searches conducted via the China National Knowledge Infrastructure (CNKI) database, the MEDLINE database, the World Health Organization (WHO) database, and MedRxiv and BioRxiv electronic platforms for preprint articles, published up until April 8th, 2020. Studies available in Chinese and English were included in the searches and extracted. A primary descriptive analysis was performed for registered clinical trials and observational studies identified in the Chinese Clinical Trial Registry based on the extraction of the following clinical study information: trial ID, planned date of enrollment, recruitment status, study design, population, sample size, intervention/exposure group, control /reference group, dosage, and primary outcomes. A secondary descriptive analysis was performed for published clinical trials and observational studies identified from the supplementary databases based on the extraction of the following published clinical study information: study design, population, intervention/exposure group, control /reference group and main results as appropriate. Results: A total of 221 clinical trials and observational studies were included from all databases searched. From the Chinese Clinical Trial Registry, 195 registered clinical studies including 170 clinical trials and 25 observational studies were identified and included for primary analysis. From the supplementary databases, 26 published clinical studies including 8 clinical trials and 18 observational studies were included for secondary analysis. Of these 26 published clinical studies, 18 studies, including 3 clinical trials and 15 observational studies were identified from CNKI, 2 studies including 1 clinical trial and 1 observational study from MEDLINE, 2 including 1 clinical trials and 1 observational studies from the WHO database, and 4 including 3 clinical trials and 1 observational studies from MedRxiv and BioRxiv platforms. In the primary analysis, among the 170 clinical trials included from the Chinese Clinical Trial Registry, 101 investigated western medicines (WMs), while 15 investigated Traditional Chinese Medicines (TCMs), and 54 investigated a combination of TCMs and WMs. Among the 25 included observational studies from the Chinese Clinical Trial Registry, 2 investigated WMs, 2 investigated TCMs, and 21 investigated a combination of TCMs and WMs. The total number of exposed patients in all 195 clinical studies from the Chinese Clinical Trial Registry amounted to 24,500. In the secondary analysis, treatment with Lopinavir-ritonavir and treatment with Hydroxychloroquine was not associated with a difference from standard of care in the rate of RT-PCR negativity; treatment with a combination of Lopinavir-ritonavir, interferon α, and Lian-Hua-Qing-Wen capsule was found to significantly improve the effective rate of treatment compared with Interferon α combined with Lian-Hua-Qing-Wen capsule. Conclusions: China is generating a massive source of evidence that is critical for defeating the COVID-19 pandemic. Not only the clinical experience, but also the scientific evidence should be shared with the global scientific community.

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Participation in Substance Abuse Clinical Trials: Comparing Gender, Racial/Ethnic, and Age Groups

PsycEXTRA Dataset ◽

10.1037/e654912011-001 ◽

2011 ◽

Author(s):

Carmen L. Rosa ◽

Paul G. Wakim ◽

Harold Perl

Keyword(s):

Substance Abuse ◽

Clinical Trials ◽

Age Groups ◽

Racial Ethnic

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Quantitative evaluation of slow fluctuations of the volume of liquids inside cranial cavity

Russian Osteopathic Journal ◽

10.32885/2220-0975-2019-1-2-51-63 ◽

2019 ◽

pp. 51-63 ◽

Cited By ~ 1

Author(s):

Yu. E. Moskalenko ◽

T. I. Kravchenko ◽

Yu. V. Novozhilova

Keyword(s):

Brain Activity ◽

Sampling Rate ◽

Age Groups ◽

Pulse Amplitude ◽

Cranial Cavity ◽

Current Frequency ◽

Physiological Indicators ◽

Physiological Phenomenon ◽

Long Time ◽

Manned Space

Introduction. Slow fl uctuations in the volume and pressure of liquids in the cranial cavity have been known for a long time and have been studied for more than 100 years. However, their quantitative indicators and their practical signifi cance remain unclear until now due to the diffi culties of research. Nevertheless, it was found that they were connected with the brain activity, which made it possible to use them as one of the physiological indicators in studying the problems of manned space fl ights. Goal of research — to study the possibility of using spectral analysis of slow fl uctuations of the volume of liquids inside the cranium in order to realize the quantitative assessment of their indicators with the use of modern microelectronics and computer technology.Materials and methods. In order to solve this problem we created a complex, in which rheoencephalograph-RG-01 («Mizar») was used as a converter-modulator of physiological signals into electrical oscillations. The device was connected with the ADC (Firm «ADIstrument»), Its software allows to calculate the spectrogram with a sampling rate of 128 kHz. Studies were conducted on volunteers of younger, middle and older age groups. The respiratory rate and the electrocardiography were registered together with the rheoencephalography. Electrodes were fi xed on the volonteers′ fronto-mastoid area.Results. Slow fl uctuations the cranium representan independent physiological phenomenon. The most considerable and valuable were fl uctuations in 0,1–0,3 Hz. It was found that current frequency of 100 or 200 kHz and frequency for quantization of 80–100 kHz was optimal for performing their spectrograms. The structure of such diagram consists of 4–7 peaks with amplitude of 0,4–0,7 units compared with REG pulse amplitude. They depend on age and are characterized by hemispheric asymmetry. Spectral diagrams of slow fl ucation inside cranium are representing inpendent physiological phenomenon. These fl uctuations are not connected by common origin, with heart activity and respiration. They are connected by nature with brain activity and PRM.Conclusion. Can be an informative method for diagnostic and assessment of general status of osteopathic patients well as for the assessment of mechanisms of action of some osteopathic techniques.

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Calling for improved quality in the registration of traditional Chinese medicine during the public health emergency: a survey of trial registries for COVID-19, H1N1, and SARS

Trials ◽

10.1186/s13063-021-05113-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhuoran Kuang ◽

◽

Xiaoyan Li ◽

Jianxiong Cai ◽

Yaolong Chen ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Secondary Outcome ◽

Specific Information ◽

Clinical Trial Registry ◽

Data Set ◽

Diagnosis Criteria

Abstract Objective To assess the registration quality of traditional Chinese medicine (TCM) clinical trials for COVID-19, H1N1, and SARS. Method We searched for clinical trial registrations of TCM in the WHO International Clinical Trials Registry Platform (ICTRP) and Chinese Clinical Trial Registry (ChiCTR) on April 30, 2020. The registration quality assessment is based on the WHO Trial Registration Data Set (Version 1.3.1) and extra items for TCM information, including TCM background, theoretical origin, specific diagnosis criteria, description of intervention, and outcomes. Results A total of 136 records were examined, including 129 severe acute respiratory syndrome coronavirus 2 (COVID-19) and 7 H1N1 influenza (H1N1) patients. The deficiencies in the registration of TCM clinical trials (CTs) mainly focus on a low percentage reporting detailed information about interventions (46.6%), primary outcome(s) (37.7%), and key secondary outcome(s) (18.4%) and a lack of summary result (0%). For the TCM items, none of the clinical trial registrations reported the TCM background and rationale; only 6.6% provided the TCM diagnosis criteria or a description of the TCM intervention; and 27.9% provided TCM outcome(s). Conclusion Overall, although the number of registrations of TCM CTs increased, the registration quality was low. The registration quality of TCM CTs should be improved by more detailed reporting of interventions and outcomes, TCM-specific information, and sharing of the result data.

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Therapeutic clinical trials to combat COVID-19 pandemic in India: analysis from trial registry

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0208 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Angelika Batta ◽

Raj Khirasaria ◽

Vinod Kapoor ◽

Deepansh Varshney

Keyword(s):

Clinical Trials ◽

De Novo ◽

Treatment Options ◽

Drug Repurposing ◽

Trial Registry ◽

Therapeutic Treatment ◽

Clinical Trial Registry ◽

Clear Cut ◽

Therapeutic Trials ◽

Microsoft Office

AbstractObjectivesWith the emergence of Novel corona virus, hunt for finding a preventive and therapeutic treatment options has already begun at a rapid pace with faster clinical development programs. The present study was carried out to give an insight of therapeutic interventional trials registered under clinical trial registry of India (CTRI) for COVID-19 pandemic.MethodsAll trials registered under CTRI were evaluated using keyword “COVID” from its inception till 9th June 2020. Out of which, therapeutic interventional studies were chosen for further analysis. Following information was collected for each trial: type of therapeutic intervention (preventive/therapeutic), treatment given, no. of centers (single center/multicentric), type of institution (government/private), study design (randomized/single-blinded/double-blinded) and sponsors (Government/private). Microsoft Office Excel 2007 was used for tabulation and analysis.ResultsThe search yielded total of 205 trials, out of which, 127 (62%) trials were interventional trials. Out of these, 71 (56%) were AYUSH interventions, 36 (28.3%) tested drugs, 9 (7%) tested a nondrug intervention, rest were nutraceuticals and vaccines. About 66 (56%) were therapeutic trials. Majority were single-centered trials, i.e. 87 (73.7%). Trials were government funded in 57 (48.3%) studies. Majority were randomized controlled trials, i.e. 67 (56.8%). AYUSH preparations included AYUSH-64, Arsenic Album, SamshamaniVati etc.ConclusionsThe number of therapeutic interventional clinical trials was fair in India. A clear-cut need exists for an increase in both quantity and quality of clinical trials for COVID-19. Drug repurposing approach in all systems of medicine can facilitate prompt clinical decisions at lower costs than de novo drug development.

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EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-220884 ◽

2021 ◽

pp. annrheumdis-2021-220884

Author(s):

Kulveer Mankia ◽

Heidi J Siddle ◽

Andreas Kerschbaumer ◽

Deshire Alpizar Rodriguez ◽

Anca Irinel Catrina ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

At Risk ◽

Clinical Trials ◽

Observational Studies ◽

Task Force ◽

Musculoskeletal Symptoms ◽

Subclinical Inflammation ◽

Consensus Statements ◽

Clinical Arthritis

BackgroundDespite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA).MethodsAn European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1–10) for each PTC.ResultsEpidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants’ knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach.ConclusionThese consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.

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Use of connected digital products in clinical research following the COVID-19 pandemic: a comprehensive analysis of clinical trials

BMJ Open ◽

10.1136/bmjopen-2020-047341 ◽

2021 ◽

Vol 11 (6) ◽

pp. e047341

Author(s):

Caroline Marra ◽

William J Gordon ◽

Ariel Dora Stern

Keyword(s):

Clinical Trials ◽

Clinical Research ◽

Outcome Measures ◽

Remote Monitoring ◽

Search Algorithm ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Digital Products ◽

Clinical Trial Registry ◽

Before And After

ObjectivesIn an effort to mitigate COVID-19 related challenges for clinical research, the US Food and Drug Administration (FDA) issued new guidance for the conduct of ‘virtual’ clinical trials in late March 2020. This study documents trends in the use of connected digital products (CDPs), tools that enable remote patient monitoring and telehealth consultation, in clinical trials both before and after the onset of the pandemic.DesignWe applied a comprehensive text search algorithm to clinical trial registry data to identify trials that use CDPs for remote monitoring or telehealth. We compared CDP use in the months before and after the issuance of FDA guidance facilitating virtual clinical trials.SettingAll trials registered on ClinicalTrials.gov with start dates from May 2019 through February 2021.Outcome measuresThe primary outcome measure was the overall percentage of CDP use in clinical trials started in the 10 months prior to the pandemic onset (May 2019–February 2020) compared with the 10 months following (May 2020–February 2021). Secondary outcome measures included CDP usage by trial type (interventional, observational), funder type (industry, non-industry) and diagnoses (COVID-19 or non-COVID-19 participants).ResultsCDP usage in clinical trials increased by only 1.65 percentage points, from 14.19% (n=23 473) of all trials initiated in the 10 months prior to the pandemic onset to 15.84% (n=26 009) of those started in the 10 months following (p<0.01). The increase occurred primarily in observational studies and non-industry funded trials and was driven entirely by CDP usage in trials for COVID-19.ConclusionsThese findings suggest that in the short-term, new options created by regulatory guidance to stimulate telehealth and remote monitoring were not widely incorporated into clinical research. In the months immediately following the pandemic onset, CDP adoption increased primarily in observational and non-industry funded studies where virtual protocols are likely medically necessary due to the participants’ COVID-19 diagnosis.

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Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

Nature Communications ◽

10.1038/s41467-021-21992-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jean-Sélim Driouich ◽

Maxime Cochin ◽

Guillaume Lingas ◽

Grégory Moureau ◽

Franck Touret ◽

...

Keyword(s):

Clinical Trials ◽

Drug Exposure ◽

Clinical Evidence ◽

Antiviral Effect ◽

Dose Effect ◽

Plasma Drug ◽

Hamster Model ◽

Viral Genomes ◽

Antiviral Efficacy ◽

Repurposed Drugs

AbstractDespite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment is initiated before or simultaneously to infection, favipiravir has a strong dose effect, leading to reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlates with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. Antiviral efficacy is achieved with plasma drug exposure comparable with those previously found during human clinical trials. Notably, the highest dose of favipiravir tested is associated with signs of toxicity in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.

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