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1.
Annu Rev Virol ; 7(1): 475-494, 2020 09 29.
Article in English | MEDLINE | ID: covidwho-865856

ABSTRACT

The conduct of clinical trials during the West Africa Ebola outbreak in 2014 highlighted many ethical challenges. How these challenges were addressed, what clinical studies were conducted during that outbreak, and the lessons learned for dealing with future outbreaks were the subject of a National Academy of Medicine committee report titled Integrating Clinical Research into Epidemic Response: The Ebola Experience. This report suggested improvements for research during subsequent emerging or re-emerging outbreaks and is summarized in this review. We also discuss the current Ebola outbreak in the Democratic Republic of the Congo and highlight how the dialogue has changed and how successful clinical trials have been implemented. We conclude with a description of productive efforts to include pregnant women and children in therapeutic and vaccine trials during outbreaks that are currently ongoing.


Subject(s)
Biomedical Research/ethics , Clinical Trials as Topic/ethics , Disease Outbreaks , Ebolavirus/pathogenicity , Hemorrhagic Fever, Ebola/epidemiology , Patient Selection/ethics , Adult , Africa, Western/epidemiology , Antiviral Agents/therapeutic use , Biomedical Research/organization & administration , Child , Clinical Trials as Topic/organization & administration , Ebola Vaccines/administration & dosage , Female , Hemorrhagic Fever, Ebola/immunology , Hemorrhagic Fever, Ebola/mortality , Hemorrhagic Fever, Ebola/prevention & control , Humans , International Cooperation , Male , Pregnancy , Survival Analysis
2.
Dtsch Med Wochenschr ; 145(20): 1464-1468, 2020 10.
Article in German | MEDLINE | ID: covidwho-834931

ABSTRACT

Vaccination practices in Germany are driven by scientific developments and a complex regulatory environment. Some important developments in 2019/20 are described here: Work-related vaccination recommendations for measles, rubella, and chickenpox have been streamlined and expanded. In addition, measles vaccination or documentation of immunity is now mandatory for employment at and attendance of many institutions, specifically including day care centers and schools. Owing to the shift of pneumococcal serotypes since the introduction of conjugate vaccines the US ACIP no longer recommends these for the routine administration to healthy persons of older age. Reduced series of 2 or even 1 dose of an HPV vaccine may be sufficient, however definitive RCT data are not yet available. After years of development and clinical studies the first vaccine against Ebolavirus disease has been licensed by EMA in November and by FDA in December 2019. More than 150 SARS-CoV-2 vaccine candidates are being developed with massive financial support, several phase 1/2 trials have started. A licensed vaccine may actually be available in 2021 and thus dramatically faster compared to any other modern vaccine development.


Subject(s)
Mass Vaccination , Vaccines , Adult , Clinical Trials as Topic , Coronavirus Infections/prevention & control , Germany , Humans , Immunization Schedule , Viral Vaccines
3.
6.
Curr Atheroscler Rep ; 22(12): 72, 2020 10 03.
Article in English | MEDLINE | ID: covidwho-812556

ABSTRACT

PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the 2020 European Society of Cardiology (ESC) Congress-The Digital Experience. RECENT FINDINGS: The studies reviewed include clinical trials on novel RNA interference-based lipid-lowering therapies AKCEA-APOCIII-LRx and vupanorsen (AKCEA-ANGPTL3-LRx); the EVAPORATE trial assessing the effects of icosapent ethyl on coronary plaque volume progression; the LoDoCo2 trial evaluating the efficacy of low-dose colchicine in cardiovascular disease risk reduction among patients with chronic coronary artery disease; as well as the EMPEROR-Reduced trial evaluating cardiovascular and renal outcomes with empagliflozin in patients with heart failure and reduced ejection fraction. In addition, we review the BPLTTC analysis on blood pressure treatment across blood pressure levels and CVD status and discuss findings from the BRACE CORONA study that examined continuing versus suspending angiotensin-converting enzyme inhibitor or angiotensin receptor blockers in patients on these antihypertensive medications who were hospitalized with COVID-19 infection. The studies presented at the 2020 digital ESC Congress highlight the continuing advancements in the field of CVD prevention.


Subject(s)
Betacoronavirus/physiology , Cardiology , Cardiovascular Agents/pharmacology , Cardiovascular Diseases , Coronavirus Infections , Lipid Regulating Agents/pharmacology , Pandemics , Pneumonia, Viral , Benzhydryl Compounds/pharmacology , Cardiology/methods , Cardiology/trends , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Clinical Trials as Topic , Congresses as Topic , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Eicosapentaenoic Acid/analogs & derivatives , Eicosapentaenoic Acid/pharmacology , Europe , Glucosides/pharmacology , Humans , Oligonucleotides/pharmacology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Societies, Medical , Telecommunications
9.
PLoS One ; 15(9): e0239694, 2020.
Article in English | MEDLINE | ID: covidwho-807018

ABSTRACT

With the novel COVID-19 pandemic disrupting and threatening the lives of millions, researchers and clinicians have been recently conducting clinical trials at an unprecedented rate to learn more about the virus and potential drugs/treatments/vaccines to treat its infection. As a result of the influx of clinical trials, researchers, clinicians, and the lay public, now more than ever, face a significant challenge in keeping up-to-date with the rapid rate of discoveries and advances. To remedy this problem, this research mined the ClinicalTrials.gov corpus to extract COVID-19 related clinical trials, produce unique reports to summarize findings and make the meta-data available via Application Programming Interfaces (APIs). Unique reports were created for each drug/intervention, Medical Subject Heading (MeSH) term, and Human Phenotype Ontology (HPO) term. These reports, which have been run over multiple time points, along with APIs to access meta-data, are freely available at http://covidresearchtrials.com. The pipeline, reports, association of COVID-19 clinical trials with MeSH and HPO terms, insights, public repository, APIs, and correlations produced are all novel in this work. The freely available, novel resources present up-to-date relevant biological information and insights in a robust, accessible manner, illustrating their invaluable potential to aid researchers overcome COVID-19 and save hundreds of thousands of lives.


Subject(s)
Biological Ontologies , Clinical Trials as Topic , Coronavirus Infections/therapy , Natural Language Processing , Pneumonia, Viral/therapy , Betacoronavirus , Computational Biology , Humans , Internet , Medical Subject Headings , Pandemics , Phenotype , Software
11.
Trials ; 21(1): 815, 2020 Sep 29.
Article in English | MEDLINE | ID: covidwho-803067

ABSTRACT

An unprecedented volume of research has been generated in response to the COVID-19 pandemic. However, there are risks of inefficient duplication and of important work being impeded if efforts are not synchronized. Excessive reliance on observational studies, which can be more rapidly conducted but are inevitably subject to measured and unmeasured confounders, can foil efforts to conduct rigorous randomized trials. These challenges are illustrated by recent global efforts to conduct clinical trials of post-exposure prophylaxis (PEP) as a strategy for preventing COVID-19. Innovative strategies are needed to help overcome these issues, including increasing communication between the Data Safety and Monitoring Committees (DSMCs) of similar trials. It is important to reinforce the primacy of high-quality trials in generating unbiased answers to pressing prevention and treatment questions about COVID-19.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Clinical Trials Data Monitoring Committees/trends , Clinical Trials as Topic , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Post-Exposure Prophylaxis , Research Design/trends , Antiviral Agents/adverse effects , Betacoronavirus/pathogenicity , Cooperative Behavior , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Host-Pathogen Interactions , Humans , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Risk Factors , Time Factors , Treatment Outcome
12.
Drug Des Devel Ther ; 14: 3803-3813, 2020.
Article in English | MEDLINE | ID: covidwho-797376

ABSTRACT

Objective: This study aimed to evaluate the pharmacological mechanisms of antiviral drugs against the novel coronavirus disease (COVID-19) and the study designs in clinical trials registered with the International Clinical Trials Registry Platform (ICTRP). Methods: Clinical trials involving antiviral drugs for treating COVID-19 were retrieved from the ICTRP database. For each trial, the study design, number of participants, primary endpoints, source register, antiviral mechanism, and results were evaluated. Results: On June 10, 2020, 145 eligible clinical trials were retrieved from the ICTRP, of which 99 (68.3%) were randomized trials, 109 (75.2%) were parallel assignment trials, 38 (26.2%) were double or single blinded, 130 (89.7%) involved two groups, and 75 (51.6%) included more than 100 participants; and clinical improvement or recovery and virus-negative conversion were the two most common endpoints, accounting for 40.7% and 18.6%, respectively. The drugs were divided according to the antiviral mechanism into HIV reverse transcriptase inhibitors, RNA-dependent RNA polymerase inhibitors, HIV protease inhibitors (PIs), hepatitis C virus NS3 PIs, and anti-influenza drugs. Conclusion: The design characteristics of clinical trials of antiviral drugs for treating COVID-19 as well as the mechanism of action and antiviral efficacy of the drugs were evaluated in this study. The results of these trials could constitute a reference for future clinical trials to be executed on COVID-19 treatment and prevention.


Subject(s)
Antiviral Agents/therapeutic use , Clinical Trials as Topic , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Registries , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Data Collection , Data Interpretation, Statistical , Data Management , Drug Combinations , Humans , Pandemics , Research Design
13.
J Nepal Health Res Counc ; 18(2): 151-158, 2020 Sep 07.
Article in English | MEDLINE | ID: covidwho-792246

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), a respiratory illness. COVID-19 has now become a global public health crisis causing alarming numbers of morbidity and mortality. Ever since the COVID-19 pandemic started scientists, researchers, universities, companies, and institutions all around the world have been endeavoring to discover a potential treatment for COVID-19. Numerous studies and clinical trials on vaccines and drugs for the prevention and treatment of COVID-19 are underway across the world. However, the uncertainty around the efficacy and safety of various treatment regimens have become one of the biggest challenges in the battle against the SARS-CoV-2. This paper is a narrative review of articles regarding the various treatments and vaccines being tested for the SARS-CoV-2, available in the PubMed database along with Google Scholar. There are ongoing clinical trials on potential drugs such as remdesivir, favipiravir, lopinavir/ritonavir, chloroquine, and hydroxychloroquine, corticosteroids tocilizumab, azithromycin, anakinra, etc. and other therapeutic modalities like convalescent plasma therapy. Likewise, vaccines against SARS-CoV-2 are being developed and tested, including mRNA, non-replicating viral vector, DNA, protein subunit candidate vaccines, etc. Although some early-stage clinical trials and studies on these drugs and vaccines have shown positive results, definitive and conclusive results are yet to be obtained. Keywords: COVID-19; antiviral drugs; COVID-19 treatment; COVID-19 vaccine; SARS-CoV-2.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Viral Vaccines , Betacoronavirus , Clinical Trials as Topic , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control
14.
JMIR Public Health Surveill ; 6(3): e19773, 2020 07 02.
Article in English | MEDLINE | ID: covidwho-791866

ABSTRACT

BACKGROUND: Routinely recorded primary care data have been used for many years by sentinel networks for surveillance. More recently, real world data have been used for a wider range of research projects to support rapid, inexpensive clinical trials. Because the partial national lockdown in the United Kingdom due to the coronavirus disease (COVID-19) pandemic has resulted in decreasing community disease incidence, much larger numbers of general practices are needed to deliver effective COVID-19 surveillance and contribute to in-pandemic clinical trials. OBJECTIVE: The aim of this protocol is to describe the rapid design and development of the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) and its first two platforms. The Surveillance Platform will provide extended primary care surveillance, while the Trials Platform is a streamlined clinical trials platform that will be integrated into routine primary care practice. METHODS: We will apply the FAIR (Findable, Accessible, Interoperable, and Reusable) metadata principles to a new, integrated digital health hub that will extract routinely collected general practice electronic health data for use in clinical trials and provide enhanced communicable disease surveillance. The hub will be findable through membership in Health Data Research UK and European metadata repositories. Accessibility through an online application system will provide access to study-ready data sets or developed custom data sets. Interoperability will be facilitated by fixed linkage to other key sources such as Hospital Episodes Statistics and the Office of National Statistics using pseudonymized data. All semantic descriptors (ie, ontologies) and code used for analysis will be made available to accelerate analyses. We will also make data available using common data models, starting with the US Food and Drug Administration Sentinel and Observational Medical Outcomes Partnership approaches, to facilitate international studies. The Surveillance Platform will provide access to data for health protection and promotion work as authorized through agreements between Oxford, the Royal College of General Practitioners, and Public Health England. All studies using the Trials Platform will go through appropriate ethical and other regulatory approval processes. RESULTS: The hub will be a bottom-up, professionally led network that will provide benefits for member practices, our health service, and the population served. Data will only be used for SQUIRE (surveillance, quality improvement, research, and education) purposes. We have already received positive responses from practices, and the number of practices in the network has doubled to over 1150 since February 2020. COVID-19 surveillance has resulted in tripling of the number of virology sites to 293 (target 300), which has aided the collection of the largest ever weekly total of surveillance swabs in the United Kingdom as well as over 3000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology samples. Practices are recruiting to the PRINCIPLE (Platform Randomised trial of INterventions against COVID-19 In older PeopLE) trial, and these participants will be followed up through ORCHID. These initial outputs demonstrate the feasibility of ORCHID to provide an extended national digital health hub. CONCLUSIONS: ORCHID will provide equitable and innovative use of big data through a professionally led national primary care network and the application of FAIR principles. The secure data hub will host routinely collected general practice data linked to other key health care repositories for clinical trials and support enhanced in situ surveillance without always requiring large volume data extracts. ORCHID will support rapid data extraction, analysis, and dissemination with the aim of improving future research and development in general practice to positively impact patient care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19773.


Subject(s)
Clinical Trials as Topic , Coronavirus Infections/epidemiology , General Practice/organization & administration , Medical Records Systems, Computerized , Pneumonia, Viral/epidemiology , Public Health Surveillance , Humans , Pandemics , Primary Health Care/organization & administration , Societies, Medical , United Kingdom/epidemiology
15.
Eur Rev Med Pharmacol Sci ; 24(17): 9169-9171, 2020 09.
Article in English | MEDLINE | ID: covidwho-790178

ABSTRACT

NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome has recently become an intriguing target of several chronic and viral diseases. Here, we argue that targeting NLRP3 inflammasome could be a strategy to prevent cardiovascular outcomes [fulminant myocarditis, heart failure, venous thromboembolism (VTE)] and acute respiratory distress syndrome (ARDS) in patients with SARS-CoV-2 infection. We discuss the rationale for NLRP3 targeting in clinical trials as an effective therapeutic strategy aimed to improve prognosis of COVID-19, analyzing the potential of two therapeutic options (tranilast and OLT1177) currently available in clinical practice.


Subject(s)
Cardiovascular Diseases/prevention & control , Coronavirus Infections/diagnosis , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pneumonia, Viral/diagnosis , Betacoronavirus/isolation & purification , Clinical Trials as Topic , Coronavirus Infections/virology , Cytokines/metabolism , Humans , Inflammasomes/metabolism , Myocarditis/prevention & control , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Nitriles/therapeutic use , Pandemics , Pneumonia, Viral/virology , Prognosis , Venous Thromboembolism/prevention & control , ortho-Aminobenzoates/therapeutic use
16.
Pan Afr Med J ; 36: 206, 2020.
Article in English | MEDLINE | ID: covidwho-789897

ABSTRACT

The intense global efforts are directed towards development of vaccines to halt the COVID-19 virus pandemic. There are 160 candidate vaccines under clinical trials across the world using different molecular targets and techniques. This race for the vaccine has several challenges and ethical issues like compressed timelines, generation and proper management of resources and finances, risks to the participating volunteers due to curtailed research trial processes, geopolitical contentions, misinformation through social media and parallel race with drugs. We feel that the fundamental principles of ethics: autonomy, beneficence, non-maleficence and justice should not be violated in this hastened vaccine development process. We recommend constitute a Consortium on a global platform to formulate, provide and monitor a comprehensive ethical umbrella to the process of vaccine development.


Subject(s)
Betacoronavirus/immunology , Clinical Trials as Topic/ethics , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/therapeutic use , Bioethical Issues , Communication , Coronavirus Infections/drug therapy , Coronavirus Infections/economics , Coronavirus Infections/epidemiology , Healthy Volunteers , Humans , Internationality , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Resource Allocation , Social Media , Time Factors , Viral Vaccines/economics , Viral Vaccines/supply & distribution
17.
J Transl Med ; 18(1): 359, 2020 09 21.
Article in English | MEDLINE | ID: covidwho-781480

ABSTRACT

More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Mesenchymal Stem Cell Transplantation , Pneumonia, Viral/therapy , Animals , Clinical Trials as Topic , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Humans , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Respiratory Distress Syndrome, Adult/etiology , Respiratory Distress Syndrome, Adult/immunology , Respiratory Distress Syndrome, Adult/therapy , Translational Medical Research
19.
BMJ Open ; 10(9): e041276, 2020 09 17.
Article in English | MEDLINE | ID: covidwho-781188

ABSTRACT

OBJECTIVES: To characterise current COVID-19-related research activities. DESIGN: Cross-sectional analysis. SETTING: Clinical trials registered with ClinicalTrials.gov testing interventions relevant to COVID-19. DATA SOURCES: ClinicalTrials.gov was searched for COVID-19 and related terms to identify trials registered between 1 December 2019 and 1 May 2020 that test interventions related to the COVID-19 pandemic. MAIN OUTCOME MEASURES: We classified trials according to intervention type, and report key trial characteristics including recruitment status, location, funder type, target enrolment number, intervention model (single group, randomised or sequential assignment) and projected completion date. RESULTS: Of the 630 identified clinical trials related to COVID-19, 509 (81%) involved the study of drugs or biological agents. Of these trials of drugs and biologics, 305 (60%) use an open-label design, 43 (8%) are single blinded (participant only) and 161 (32%) are double blinded (participant and investigator). 94 (18%) of the drug/biological trials are non-randomised. Either hydroxychloroquine or chloroquine is administered as part of the study protocol in 152 (30%) of the drug/biological trials. The total planned enrolment for these hydroxychloroquine/chloroquine trials is over 200 000 participants, which represents 65% of the total planned enrolment for all registered trials of drugs or biologics. There are also at least 25 registered trials of azithromycin (n=53), convalescent plasma (n=38), lopinavir/ritonavir (n=30), stem cell treatments (n=29) and tocilizumab (n=25). 142 trials were registered in the first 3 months of 2020, and 488 trials were registered between 1 April and 1 May 2020. CONCLUSIONS: These findings demonstrate a robust research response to the COVID-19 pandemic, though many of the currently planned and ongoing trials focus on a small number of potential therapies, and many also lack essential design features and power necessary to provide accurate treatment effect estimates.


Subject(s)
Antiviral Agents/therapeutic use , Clinical Trials as Topic , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Registries , Stem Cell Transplantation , Antibodies, Monoclonal, Humanized/therapeutic use , Azithromycin/therapeutic use , Betacoronavirus , Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Double-Blind Method , Drug Combinations , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Lopinavir/therapeutic use , Pandemics , Ritonavir/therapeutic use , Single-Blind Method
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