scholarly journals A Scoping Insight on Potential Prophylactics, Vaccines and Therapeutic Weaponry for the Ongoing Novel Coronavirus (COVID-19) Pandemic- A Comprehensive Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Priyanka Dash ◽  
Subhashree Mohapatra ◽  
Sayantan Ghosh ◽  
Bismita Nayak
Keyword(s):  
Clinical Trials ◽  
Therapeutic Strategy ◽  
Antiviral Agents ◽  
Fast Response ◽  
Etiologic Agent ◽  
Prolonged Treatment ◽  
Rdrp Activity ◽  
Open Label ◽  
Plasma Therapy ◽  
Mesenchymal Stem Cell Therapy

The emergence of highly virulent CoVs (SARS-CoV-2), the etiologic agent of novel ongoing “COVID-19” pandemics has been marked as an alarming case of pneumonia posing a large global healthcare crisis of unprecedented magnitude. Currently, the COVID-19 outbreak has fueled an international demand in the biomedical field for the mitigation of the fast-spreading illness, all through the urgent deployment of safe, effective, and rational therapeutic strategies along with epidemiological control. Confronted with such contagious respiratory distress, the global population has taken significant steps towards a more robust strategy of containment and quarantine to halt the total number of positive cases but such a strategy can only delay the spread. A substantial number of potential vaccine candidates are undergoing multiple clinical trials to combat COVID-19 disease, includes live-attenuated, inactivated, viral-vectored based, sub-unit vaccines, DNA, mRNA, peptide, adjuvant, plant, and nanoparticle-based vaccines. However, there are no licensed anti-COVID-19 drugs/therapies or vaccines that have proven to work as more effective therapeutic candidates in open-label clinical trial studies. To counteract the infection (SARS-CoV-2), many people are under prolonged treatment of many chemical drugs that inhibit the PLpro activity (Ribavirin), viral proteases (Lopinavir/Ritonavir), RdRp activity (Favipiravir, Remdesivir), viral membrane fusion (Umifenovir, Chloroquine phosphate (CQ), Hydroxychloroquine phosphate (HCQ), IL-6 overexpression (Tocilizumab, Siltuximab, Sarilumab). Mesenchymal Stem Cell therapy and Convalescent Plasma Therapy have emerged as a promising therapeutic strategy against SARS-CoV-2 virion. On the other hand, repurposing previously designed antiviral agents with tolerable safety profile and efficacy could be the only promising approach and fast response to the novel virion. In addition, research institutions and corporations have commenced the redesign of the available therapeutic strategy to manage the global crisis. Herein, we present succinct information on selected anti-COVID-19 therapeutic medications repurposed to combat SARS-CoV-2 infection. Finally, this review will provide exhaustive detail on recent prophylactic strategies and ongoing clinical trials to curb this deadly pandemic, outlining the major therapeutic areas for researchers to step in.

scholarly journals An Update on Antiviral Therapy Against SARS-CoV-2: How Far Have We Come?

2021 ◽  
Vol 12 ◽  
Author(s):  
Omkar Indari ◽  
Shweta Jakhmola ◽  
Elangovan Manivannan ◽  
Hem Chandra Jha
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Drug Repurposing ◽  
Clinical Findings ◽  
Open Label ◽  
Plasma Therapy ◽  
Clinical Safety ◽  
Treatment Research ◽  
Repurposed Drugs ◽  
Approved Drugs

COVID-19 pandemic has spread worldwide at an exponential rate affecting millions of people instantaneously. Currently, various drugs are under investigation to treat an enormously increasing number of COVID-19 patients. This dreadful situation clearly demands an efficient strategy to quickly identify drugs for the successful treatment of COVID-19. Hence, drug repurposing is an effective approach for the rapid discovery of frontline arsenals to fight against COVID-19. Successful application of this approach has resulted in the repurposing of some clinically approved drugs as potential anti-SARS-CoV-2 candidates. Several of these drugs are either antimalarials, antivirals, antibiotics or corticosteroids and they have been repurposed based on their potential to negate virus or reduce lung inflammation. Large numbers of clinical trials have been registered to evaluate the effectiveness and clinical safety of these drugs. Till date, a few clinical studies are complete and the results are primary. WHO also conducted an international, multi-country, open-label, randomized trials-a solidarity trial for four antiviral drugs. However, solidarity trials have few limitations like no placebos were used, additionally any drug may show effectiveness for a particular population in a region which may get neglected in solidarity trial analysis. The ongoing randomized clinical trials can provide reliable long-term follow-up results that will establish both clinical safety and clinical efficacy of these drugs with respect to different regions, populations and may aid up to worldwide COVID-19 treatment research. This review presents a comprehensive update on majorly repurposed drugs namely chloroquine, hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, ribavirin, azithromycin, umifenovir, oseltamivir as well as convalescent plasma therapy used against SARS-CoV-2. The review also summarizes the data recorded on the mechanism of anti-SARS-CoV-2 activity of these repurposed drugs along with the preclinical and clinical findings, therapeutic regimens, pharmacokinetics, and drug-drug interactions.

scholarly journals A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19

2020 ◽  
Author(s):  
Drifa Belhadi ◽  
Nathan Peiffer-Smadja ◽  
François-Xavier Lescure ◽  
Yazdan Yazdanpanah ◽  
France Mentré ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Data Extraction ◽  
Antiviral Agents ◽  
Median Number ◽  
Antiviral Drugs ◽  
Open Label ◽  
Double Blind ◽  
Stem Cells Therapy ◽  
Novel Coronavirus

ABSTRACTBackgroundAlthough a number of antiviral agents have been evaluated for coronaviruses there are no approved drugs available. To provide an overview of the landscape of therapeutic research for COVID-19, we conducted a review of registered clinical trials.MethodsA review of currently registered clinical trials was performed on registries, including the Chinese (chictr.org.cn) and US (clinicaltrials.gov) databases to identify relevant studies up to March, 7th 2020. The search was conducted using the search terms “2019-nCoV”, “COVID-19”, “SARS-CoV-2”, “Hcov-19”, “new coronavirus”, “novel coronavirus”. We included interventional clinical trials focusing on patients with COVID-19 and assessing antiviral drugs or agents.FindingsOut of the 353 studies identified, 115 clinical trials were selected for data extraction. Phase IV trials were the most commonly reported study type (n=27, 23%). However, 62 trials (54%) did not describe the phase of the study. Eighty percent (n=92) of the trials were randomized with parallel assignment and the median number of planned inclusions was 63 (IQR, 36-120). Open-label studies were the most frequent (46%) followed by double-blind (13%) and single blind studies (10%). The most frequently assessed therapies were: stem cells therapy (n=23 trials), lopinavir/ritonavir (n=15), chloroquine (n=11), umifenovir (n=9), hydroxychloroquine (n=7), plasma treatment (n=7), favipiravir (n=7), methylprednisolone (n=5), and remdesivir (n=5). Remdesivir was tested in 5 trials with a median of 400 (IQR, 394-453) planned inclusions per trial, while stem cells therapy was tested in 23 trials, but had a median of 40 (IQR, 23-60) planned inclusions per trial. Lopinavir/ritonavir was associated with the highest total number of planned inclusions (2606) followed by remdesivir (2155). Only 52% of the clinical trials reported the treatment dose (n=60) and only 34% (n=39) the duration. The primary outcome was clinical in 76 studies (66%), virological in 27 (23%); radiological in 9 (8%) or immunological in three studies (3%).InterpretationNumerous clinical trials have been registered since the beginning of the COVID-19 outbreak, however, a number of information regarding drugs or trial design were lacking.FundingNone

scholarly journals Current Therapies in Clinical Trials of Parkinson’s Disease: A 2021 Update

2021 ◽  
Vol 14 (8) ◽  
pp. 717
Author(s):  
E. Maruthi Prasad ◽  
Shih-Ya Hung
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Therapeutic Strategy ◽  
Neurodegenerative Disorder ◽  
The United States ◽  
Herbal Extract ◽  
Phase Iii ◽  
Plasma Therapy ◽  
New Therapeutic Approaches

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that currently has no cure, but treatments are available to improve PD symptoms and maintain quality of life. In 2020, about 10 million people worldwide were living with PD. In 1970, the United States Food and Drug Administration approved the drug levodopa as a dopamine replacement to manage PD motor symptoms; levodopa-carbidopa combination became commercialized in 1975. After over 50 years of use, levodopa is still the gold standard for PD treatment. Unfortunately, levodopa therapy-induced dyskinesia and OFF symptoms remain unresolved. Therefore, we urgently need to analyze each current clinical trial’s status and therapeutic strategy to discover new therapeutic approaches for PD treatment. We surveyed 293 registered clinical trials on ClinicalTrials.gov from 2008 to 16 June 2021. After excluded levodopa/carbidopa derivative add-on therapies, we identified 47 trials as PD treatment drugs or therapies. Among them, 19 trials are in phase I (41%), 25 trials are in phase II (53%), and 3 trials are in phase III (6%). The three phase-III trials use embryonic dopamine cell implant, 5-HT1A receptor agonist (sarizotan), and adenosine A2A receptor antagonist (caffeine). The therapeutic strategy of each trial shows 29, 5, 1, 5, 5, and 2 trials use small molecules, monoclonal antibodies, plasma therapy, cell therapy, gene therapy, and herbal extract, respectively. Additionally, we discuss the most potent drug or therapy among these trials. By systematically updating the current trial status and analyzing the therapeutic strategies, we hope this review can provide new ideas and insights for PD therapy development.

scholarly journals Scaling Up: Multisite Open-Label Clinical Trials of MDMA-Assisted Therapy for Severe Posttraumatic Stress Disorder

2021 ◽  
pp. 002216782110236
Author(s):  
Julie B. Wang ◽  
Jessica Lin ◽  
Leah Bedrosian ◽  
Allison Coker ◽  
Ilsa Jerome ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Clinical Trials ◽  
Posttraumatic Stress ◽  
Clinical Supervision ◽  
Stress Disorder ◽  
The United States ◽  
Health Condition ◽  
Open Label ◽  
Adverse Health Outcomes ◽  
Ptsd Symptom Severity

Background: Posttraumatic stress disorder (PTSD) is a debilitating mental health condition associated with serious adverse health outcomes and functional impairment. Previous MDMA–assisted therapy (MDMA-AT) studies have shown promising results in single site studies. Two open-label studies tested this modality in multisite clinical trials to assess the feasibility of scaling this manualized therapy across 14 North American sites. Method: Cotherapist dyads were trained in the manualized MDMA-AT protocol and administered three experimental sessions 3 to 5 weeks apart among participants with severe PTSD. Cotherapist dyads were provided clinical supervision and evaluated for protocol adherence by centralized raters. Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) assessed change in symptoms severity. Results: Adherence rating scores were high across cotherapist dyads ( M = 95.08%, SD = 3.70%) and sites ( M = 95.23%, SD = 2.20%). CAPS-5 scores decreased following 3 MDMA-AT sessions at 18 weeks post baseline (Δ M = −29.99, Δ SD = 13.45, p < .0001, n = 37, Cohen’s d = 2.2, confidence interval [1.97, 2.47]). MDMA was well tolerated. Conclusions: These findings corroborate previous results that MDMA-AT can achieve significant improvements in PTSD symptom severity and demonstrate scalability of manualized therapy across clinic sites in the United States and Canada.

scholarly journals Effects of open-label placebos in clinical trials: a systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Melina von Wernsdorff ◽  
Martin Loef ◽  
Brunna Tuschen-Caffier ◽  
Stefan Schmidt
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Medical Condition ◽  
Data Extraction ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Open Label ◽  
Cancer Related Fatigue ◽  
Promising Treatment ◽  
Irritable Bowel

AbstractOpen-label placebos (OLPs) are placebos without deception in the sense that patients know that they are receiving a placebo. The objective of our study is to systematically review and analyze the effect of OLPs in comparison to no treatment in clinical trials. A systematic literature search was carried out in February 2020. Randomized controlled trials of any medical condition or mental disorder comparing OLPs to no treatment were included. Data extraction and risk of bias rating were independently assessed. 1246 records were screened and thirteen studies were included into the systematic review. Eleven trials were eligible for meta-analysis. These trials assessed effects of OLPs on back pain, cancer-related fatigue, attention deficit hyperactivity disorder, allergic rhinitis, major depression, irritable bowel syndrome and menopausal hot flushes. Risk of bias was moderate among all studies. We found a significant overall effect (standardized mean difference = 0.72, 95% Cl 0.39–1.05, p < 0.0001, I2 = 76%) of OLP. Thus, OLPs appear to be a promising treatment in different conditions but the respective research is in its infancy. More research is needed, especially with respect to different medical and mental disorders and instructions accompanying the OLP administration as well as the role of expectations and mindsets.

scholarly journals Effectiveness of Antimicrobial Filter Placement in ICU Taps to Prevent the Occurrence of HAIs by Pseudomonas aeruginosa (12-Months)

2020 ◽  
Vol 41 (S1) ◽  
pp. s206-s207
Author(s):  
Pablo Chico-Sánchez ◽  
Sandra Canovas-Javega ◽  
Natali J. Jimenez-Sepulveda ◽  
Edith Leutscher-Vasen ◽  
Cesar O. Villanueva-Ruiz ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Critical Care ◽  
Etiologic Agent ◽  
Incidence Density ◽  
Healthcare Associated Infections ◽  
Open Label ◽  
Filter Placement ◽  
Critical Care Units ◽  
Definition Of ◽  
Healthcare Associated

Background:Pseudomonas aeruginosa, is the third etiologic agent of healthcare associated infections, and the most frequent pathogen in ventilator-associated pneumonia (VAP). In critical care units is associated with high mortality, long hospital stay, and high healthcare-associated costs. We evaluated the effectiveness of filter placement in the water taps in critical care units to prevent the occurrence of healthcare-associated infections (HAIa) by Pseudomonas aeruginosa. Methods: This experimental study was both cross-over and open-label in nature. We included patients admitted for >24 hours in critical care units over 24 months. The study was divided into 4 periods of 6 months each. We divided the study into 2 groups: patients in units with filters and patients in units without filters. We compared the incidence density of P. aeruginosa HAIs (number of cases divided by the number of person days) according the ECDC definition of case criteria between the groups. The 2 test was used, and the magnitude of the association was calculated as a rate ratio with a 95% confidence interval, adjusted using a Poisson regression model. Results: Overall, 1,132 patients were included in the study: 595 in units with water tap filters and 537 in units without water tap filters. HAI incidence among patients in units with water tap filters was 5.3 per 1,000 person days stay; without water tap filters, HAI incidence was 4.7 per 1,000 person days stay (HR, 0.94; 95% CI, 0.47–1.90). Conclusions: The preliminary results of this study indicate a a lower incidence of P. aeruginosa HAIs in units with filters placed in water taps than in units without filters.Disclosures: NoneFunding: None

scholarly journals Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manaf AlQahtani ◽  
Abdulkarim Abdulrahman ◽  
Abdulrahman Almadani ◽  
Salman Yousif Alali ◽  
Alaa Mahmood Al Zamrooni ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Severe Disease ◽  
Pilot Trial ◽  
Standard Of Care ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Open Label ◽  
Plasma Therapy

AbstractConvalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p < 0.05) though respiratory indices did not differ. The primary outcome measure was required in 6 controls and 4 patients on CP (risk ratio 0.67, 95% CI 0.22–2.0, p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.

scholarly journals Dutch Breast Cancer Trialists' Group (BOOG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 61-79
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Phase Iii ◽  
List Type ◽  
First Line ◽  
Open Label ◽  
Phase Iii Study

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Dutch breast cancer trialists' group (BOOG). Clinical trials include:An open label randomized (inter)national multicenter comparative trial of 5 years adjuvant endocrine therapy with an LHRH agonist plus an aromatase inhibitor (goserelin + anastrozole) versus five courses FE90C chemotherapy followed by the same endocrine therapy in pre- or perimenopausal patients with hormone receptor-positive primary breast cancer (PRemenopausal Optimal Management IS Endocrine therapy). BOOG 2002-01/PROMISE. ISRCTN23561723Open label, comparative, randomized, multicenter, study of trastuzumab (Herceptin) given with docetaxel (Taxotere) versus sequential single agent therapy with trastuzumab followed by docetaxel as first-line treatment for metastatic breast cancer (MBC) patients with HER2neu overexpression. BOOG 2002-02/HERTAX ISRCTN13770586Micro-metastases and Isolated tumour cells: Robust and Relevant Or Rubbish? The MIRROR study in BREAST CANCER. BOOG 2003-03/ZonMW 3214Radiation dose intensity study in breast cancer in young women: a randomized phase III trial of additional dose to the tumor bed. BOOG 2004-01/Young Boost SRCTN45066831Microarray analysis in breast cancer to Tailor Adjuvant Drugs Or Regimens, a randomized phase III study. MATADOR, BOOG 2005-02, CKTO 2004-04 ISRCTN61893718A prospective randomised, open, multicentre, phase III study to assess different Durations of Anastrozole therapy after 2–3 years Tamoxifen as Adjuvant therapy in postmenopausal women with breast cancer. 2006-01/DATAA randomized, open-label phase III study of first line chemotherapy in elderly metastatic breast cancer patients, comparing intravenous pegylated liposomal doxorubicin with oral capecitabine; and the incorporation of a complete geriatric assessment. 2006-02/OMEGABOOG participation in International studies:. BOOG 2001-01/TEAM trial. BOOG 2001-02/AMAROS (EORTC 10981/22023). BOOG 2002-04/HERA (BIG 1-01/EORTC 10011/BO16348B). BOOG 2003-02 (BIG 1-02/IBCSG 27-02). BOOG 2003-04 (GBG 29). BOOG 2004-02/TBP (GBG 26, BIG 3-05). BOOG 2005-01/CASA (IBCSG 32-05/BIG 1-05). BOOG 2005-03/MINDACT (EORTC 10041, BIG 3-04). BOOG 2006-03/SUPREMO (BIG 2-04). BOOG 2006-04/Adjuvant lapatinib study (BIG 2-06/EGF106708)

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.

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