scholarly journals Review of Current Evidence of Hydroxychloroquine in Pharmacotherapy of COVID-19

2020 ◽  
Author(s):  
Umesh Devappa Suranagi ◽  
Harmeet Singh Rehan ◽  
Nitesh Goyal
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
In Vitro Study ◽  
Human Studies ◽  
Current Evidence ◽  
Viral Inhibition ◽  
Open Label ◽  
Clinical Trial Registries ◽  
The World

ABSTRACTImportanceThe COVID-19 Pandemic has literally left the world breathless in the chase for pharmacotherapy. With vaccine and novel drug development in early clinical trials, repurposing of existing drugs takes the center stage.ObjectiveA potential drug discussed in global scientific community is hydroxychloroquine. We intend to systematically explore, analyze, rate the existing evidence of hydroxychloroquine in the light of published, unpublished and clinical trial data.Evidence reviewPubMed Ovid MEDLINE, EMBASE, Google scholar databases, pre-proof article repositories, clinical trial registries were comprehensively searched with focused question of use of hydroxychloroquine in COVID-19 patients. The literature was systematically explored as per PRISMA guidelines.FindingsTotal 139 articles were available as of 25th April 2020; of which 10 articles of relevance were analyzed. Three in-vitro studies were reviewed. Two open label non-randomized trials, two open label randomized control trials, one follow-up study and two retrospective cohort studies were systematically analyzed and rated by oxford CEBM and GRADE framework for quality and strength of evidence. Also 27 clinical trials registered in three clinical trial registries were analyzed and summarized. Hydroxychloroquine seems to be efficient in inhibiting SARS-CoV-2 in in-vitro cell lines. However, there is lack of strong evidence from human studies. It was found that overall quality of available evidence ranges from ‘very low’ to ‘low’.Conclusions and relevanceThe in-vitro cell culture based data of viral inhibition does not suffice for the use of hydroxychloroquine in the patients with COVID-19. Current literature shows inadequate, low level evidence in human studies. Scarcity of safety and efficacy data warrants medical communities, health care agencies and governments across the world against the widespread use of hydroxychloroquine in COVID-19 prophylaxis and treatment, until robust evidence becomes available.KEY POINTSQuestionWhat is the current evidence for use of Hydroxychloroquine in pharmacotherapy of COVID-19?FindingsWe electronically explored various databases and clinical trial registries and identified 10 publications and 27 clinical trials with active recruitment. The in-vitro study data demonstrates the viral inhibition by hydroxychloroquine. The clinical studies are weakly designed and conducted with insufficient reporting and significant limitations. Well designed robust clinical trials are being conducted all over the world and results of few such robust studies are expected shortly.MeaningCurrent evidence stands inadequate to support the use of hydroxychloroquine in pharmacotherapy of COVID-19.

Melatonin reduces the mortality of severely-infected COVID-19 patients

2021 ◽  
Vol 4 (4) ◽  
pp. 613-616
Author(s):  
Dun-Xian Tan ◽  
Russel J Reiter
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Mortality Rate ◽  
Randomized Clinical Trial ◽  
Control Group ◽  
Mortality Reduction ◽  
Single Center ◽  
Open Label ◽  
Melatonin Treatment ◽  
The World

SARS-CoV-2 has ravaged the population of the world for two years. Scientists have not yet identified an effective therapy to reduce the mortality of severe COVID-19 patients. In a single-center, open-label, randomized clinical trial, it was observed that melatonin treatment lowered the mortality rate by 93% in severely-infected COVID-19 patients compared with the control group (see below). This is seemingly the first report to show such a huge mortality reduction in severe COVID-19 infected individuals with a simple treatment. If this observation is confirmed by more rigorous clinical trials, melatonin could become an important weapon to combat this pandemic.

scholarly journals Therapeutic Application of Chloroquine and Hydroxychloroquine in Clinical Trials for COVID-19: A systematic review

2020 ◽  
Author(s):  
Divya RSJB Rana ◽  
Santosh Dulal
Keyword(s):  
Public Health ◽  
Systematic Review ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Virus Disease ◽  
Global Public Health ◽  
Therapeutic Application ◽  
Clinical Trial Registries ◽  
Corona Virus

AbstractThe corona virus disease -2019 (COVID-19) pandemic has caused a massive global public health havoc. Recent published clinical trials show conflicting data for use of chloroquine/hydroxychloroquine for COVID-19. This study meticulously evaluated the various dosages of chloroquine and hydroxychloroquine utilized in clinical trials registered in Chinese and US clinical trial registries for the treatment of pneumonia caused by SARS-CoV-2. Moreover, the results of published clinical trials and in vitro studies using chloroquine and hydroxychloroquine relevant to the disease are discussed.

scholarly journals Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Iwein Gyselinck ◽  
◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

scholarly journals Reporting of harms in oncological clinical study reports submitted to the European Medicines Agency compared to trial registries and publications—a methodological review

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Asger S. Paludan-Müller ◽  
Perrine Créquit ◽  
Isabelle Boutron
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Study ◽  
Primary Source ◽  
European Medicines Agency ◽  
Clinical Trial Registries ◽  
Number Of Patients ◽  
Journal Publications ◽  
Clinical Study Reports ◽  
Completeness Of Reporting

Abstract Background An accurate and comprehensive assessment of harms is a fundamental part of an accurate weighing of benefits and harms of an intervention when making treatment decisions; however, harms are known to be underreported in journal publications. Therefore, we sought to compare the completeness of reporting of harm data, discrepancies in harm data reported, and the delay to access results of oncological clinical trials between three sources: clinical study reports (CSRs), clinical trial registries and journal publications. Methods We used the EMA clinical data website to identify all trials submitted to the EMA between 2015 and 2018. We retrieved all CSRs and included all phase II, II/III or III randomised controlled trials (RCTs) assessing targeted therapy and immunotherapy for cancer. We then identified related records in clinical trial registries and journals. We extracted harms data for eight pre-specified variables and determined the completeness of reporting of harm data in each of the three sources. Results We identified 42 RCTs evaluating 13 different drugs. Results were available on the EMA website in CSRs for 37 (88%) RCTs, ClinicalTrials.gov for 36 (86%), the European Clinical Trials Register (EUCTR) for 20 (48%) and in journal publications for 32 (76%). Harms reporting was more complete in CSRs than other sources. We identified marked discrepancies in harms data between sources, e.g. the number of patients discontinuing due to adverse events differed in CSRs and clinical trial registers for 88% of trials with data in both sources. For CSRs and publications, the corresponding number was 90%. The median (interquartile range) delay between the primary trial completion date and access to results was 4.34 (3.09–7.22) years for CSRs, 2.94 (1.16–4.52) years for ClinicalTrials.gov, 5.39 (4.18–7.33) years for EUCTR and 2.15 (0.64–5.04) years for publications. Conclusions Harms of recently approved oncological drugs were reported more frequently and in more detail in CSRs than in trial registries and journal publications. Systematic reviews seeking to address harms of oncological treatments should ideally use CSRs as the primary source of data; however, due to problems with access, this is currently not feasible.

scholarly journals Results availability and timeliness of registered COVID-19 clinical trials: interim cross-sectional results from the DIRECCT study

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e053096
Author(s):  
Maia Salholz-Hillel ◽  
Peter Grabitz ◽  
Molly Pugh-Jones ◽  
Daniel Strech ◽  
Nicholas J DeVito
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Journal Article ◽  
Cross Sectional Study ◽  
Sensitivity Analyses ◽  
Cross Sectional ◽  
Registration Data ◽  
Clinical Trial Registries ◽  
Treatment And Prevention

ObjectiveTo examine how and when the results of COVID-19 clinical trials are disseminated.DesignCross-sectional study.SettingThe COVID-19 clinical trial landscape.Participants285 registered interventional clinical trials for the treatment and prevention of COVID-19 completed by 30 June 2020.Main outcome measuresOverall reporting and reporting by dissemination route (ie, by journal article, preprint or results on a registry); time to reporting by dissemination route.ResultsFollowing automated and manual searches of the COVID-19 literature, we located 41 trials (14%) with results spread across 47 individual results publications published by 15 August 2020. The most common dissemination route was preprints (n=25) followed by journal articles (n=18), and results on a registry (n=2). Of these, four trials were available as both a preprint and journal publication. The cumulative incidence of any reporting surpassed 20% at 119 days from completion. Sensitivity analyses using alternate dates and definitions of results did not appreciably change the reporting percentage. Expanding minimum follow-up time to 3 months increased the overall reporting percentage to 19%.ConclusionCOVID-19 trials completed during the first 6 months of the pandemic did not consistently yield rapid results in the literature or on clinical trial registries. Our findings suggest that the COVID-19 response may be seeing quicker results disclosure compared with non-emergency conditions. Issues with the reliability and timeliness of trial registration data may impact our estimates. Ensuring registry data are accurate should be a priority for the research community during a pandemic. Data collection is underway for the next phase of the DIssemination of REgistered COVID-19 Clinical Trials study expanding both our trial population and follow-up time.

scholarly journals Current status of therapeutic approaches and vaccines for SARS-CoV-2

2021 ◽  
Author(s):  
Braira Wahid ◽  
Anam Amir ◽  
Ayesha Ameen ◽  
Muhammad Idrees
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Review Article ◽  
Experimental Designs ◽  
Current Status ◽  
Therapeutic Approaches ◽  
Efficacious Treatment ◽  
Rapid Pace ◽  
Global Health Challenge

SARS-CoV-2, declared a pandemic in March 2020, is the current global health challenge. The global bioburden of this virus is increasing at a rapid pace. Many antiviral drugs and vaccines have been registered for clinical trials because of their inhibitory activity observed in vitro. Currently, five types of vaccines have successfully passed Phase IV clinical trial and are being administered in populations worldwide. A plethora of experimental designs have been proposed worldwide in order to find a safe and efficacious treatment option. Therefore, it is necessary to provide baseline data and information to clinicians and researchers so that they can review the current status of therapeutics and efficacy of already developed vaccines. This review article summarizes all therapeutic options that may help to combat SARS-CoV-2.

scholarly journals Expanded mesenchymal stem cell transplantation is safe in both local injection and vein transfusion

2017 ◽  
Vol 4 (3-4) ◽  
pp. 234-235 ◽  
Author(s):  
Vlassov V Salval ◽  
Yone Moto
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Clinical Applications ◽  
Local Injection ◽  
Mesenchymal Stem Cell Transplantation ◽  
Routine Treatment ◽  
Drug Products ◽  
The World

More than 500 clinical trials are using mesenchymal stem cells (MSCs) in the world to treat some different diseases. The safety of expanded MSC transplantation is the most important thing to ensure that this therapy can become the routine treatment for human diseases. More than five MSCs based stem cell drug products are approved at various countries demonstrated that expanded MSCs are safe in both local injection and transfusion. Moreover, some recent reports for 5 and 10 years followed-up clinical trials using expanded MSCs confirmed that there is not different tumorigenesis between the patients with and without expanded MSC transplantation. This letter aims to provide some evidences about the safety of expanded MSCs in clinical applications. However, the MSC quality should be stritcly controlled during the in vitro MSC expansion.

scholarly journals Preferences of Adult Patients With Inflammatory Bowel Disease for Attributes of Clinical Trials: Evidence From a Choice-Based Conjoint Analysis

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Dallas Wood ◽  
Katherine Kosa ◽  
Derek Brown ◽  
Orna G Ehrlich ◽  
Peter D R Higgins ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Bowel Disease ◽  
Latent Class ◽  
Open Label ◽  
Monetary Compensation ◽  
Open Label Extension ◽  
Inflammatory Bowel ◽  
New Treatments

Abstract Background Clinical trial recruitment is the rate-limiting step in developing new treatments. To understand inflammatory bowel disease (IBD) patient recruitment, we investigated two questions: Do changes in clinical trial attributes, like monetary compensation, influence recruitment rates, and does this influence differ across subgroups? Methods We answered these questions through a conjoint survey of 949 adult IBD patients. Results Recruitment rates are influenced by trial attributes: small but significant increases are predicted with lower placebo rates, reduced number of endoscopies, less time commitment, open label extension, and increased involvement of participant’s primary GI physician. A much stronger effect was found with increased monetary compensation. Latent class analysis indicated three patient subgroups: some patients quite willing to participate in IBD trials, some quite reluctant, and others who can be persuaded. The persuadable group is quite sensitive to monetary compensation, and payments up to US$2,000 for a 1-year study could significantly increase recruitment rates for IBD clinical trials. Conclusions This innovative study provides researchers with a framework for predicting recruitment rates for different IBD clinical trials.

scholarly journals Comparison of Repeated Doses of Ivermectin Versus Ivermectin Plus Albendazole for the Treatment of Onchocerciasis: A Randomized, Open-label, Clinical Trial

2019 ◽  
Vol 71 (4) ◽  
pp. 933-943 ◽  
Author(s):  
Linda Batsa Debrah ◽  
Ute Klarmann-Schulz ◽  
Jubin Osei-Mensah ◽  
Bettina Dubben ◽  
Kerstin Fischer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Single Dose ◽  
Combination Treatment ◽  
Primary Outcome ◽  
Onchocerca Volvulus ◽  
Open Label ◽  
Annual Treatment ◽  
Repeated Doses ◽  
Better Than

Abstract Background Improved treatment for onchocerciasis is needed to accelerate onchocerciasis elimination in Africa. Aiming to better exploit registered drugs, this study was undertaken to determine whether annual or semiannual treatment with ivermectin (IVM; 200 µg/kg) plus albendazole (ALB; 800 mg single dose) is superior to IVM alone. Methods This trial was performed in Ghana and included 272 participants with microfilariae (MF), who were randomly assigned to 4 treatment arms: (1) IVM annually at 0, 12, and 24 months; (2) IVM semiannually at 0, 6, 12, 18, and 24 months; (3) IVM+ALB annually; or (4) IVM+ALB semiannually. Microfiladermia was determined pretreatment and at 6, 18, and 36 months. The primary outcome was the proportion of fertile and viable female worms in onchocercomata excised at 36 months. Results Posttreatment nodule histology showed that 15/135 (11.1%), 22/155 (14.2%), 35/154 (22.7%), and 20/125 (16.0%) living female worms had normal embryogenesis in the IVM annual, IVM semiannual, IVM+ALB annual, and IVM+ALB semiannual groups, respectively (P = .1229). Proportions of dead worms also did not differ between the 4 groups (P = .9198). Proportions of patients without MF at 36 months (1 year after the last treatment) were 35/56 (63%) after annual IVM, 42/59 (71%) after semiannual IVM, 39/64 (61%) after annual IVM+ALB, and 43/53 (81%) after semiannual IVM+ALB. Conclusions The combination treatment of IVM plus ALB was no better than IVM alone for sterilizing, killing adult worms, or achieving sustained MF clearance. However, semiannual treatment was superior to annual treatment for achieving sustained clearance of Onchocerca volvulus MF from the skin (P = .024). Clinical Trials Registration ISRCTN50035143

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