A review of the rational and current evidence on colchicine for COVID-19

2021 ◽  
Vol 27 ◽  
Author(s):  
Hazem S. Ghaith ◽  
Mohamed Diaa Gabra ◽  
Mohamed H. Nafady ◽  
Hamza Emad Elshawah ◽  
Ahmed Negida ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mechanisms Of Action ◽  
Current Evidence ◽  
Efficacy Data ◽  
Scientific Communities ◽  
The World ◽  
Clinical Benefits ◽  
Hospital Stays ◽  
Anti Inflammatory ◽  
Robust Evidence

: The current coronavirus disease (COVID-19) pandemic has affected about 247 million individuals around the world. Despite the extensive research efforts, there are currently few therapeutic options that offer direct clinical benefits for COVID-19 patients. Despite the advances in our understanding of COVID-19, the mortality rates remain significantly high owing to the high viral transmission in several countries and the rise of various mutations in the SARS-CoV-2. One of the currently available and widely used drugs that combine both anti-inflammatory and immunomodulatory actions is colchicine, which has been proposed as a possible treatment option for COVID-19. Colchicine still did not get much attention from the medical and scientific communities despite its anti-inflammatory and immunomodulatory mechanisms of action and its positive preliminary data from early trials. This literature review article provides the scientific rationale for repurposing colchicine as a potential therapeutic of COVID-19. Further, we summarize its mechanisms of action and possible roles in COVID-19 patients. Finally, we supplement this review with a summary of the doses, side effects, and the early efficacy data from clinical trials to date. Despite the early promising findings from multiple observational and clinical trials about the potential of Colchicine in COVID-19, data from the RECOVERY trial, the largest COVID-19 RCT in the world, showed no evidence of clinical benefits in mortality, hospital stays, or disease progression (n=11340 patients). However, multiple other smaller clinical trials showed significant clinical benefits. We conclude that while current evidence does not support the use of colchicine for treating COVID-19, the present body of evidence is heterogeneous and inconclusive. The drug cannot be used in clinical practice or abandoned from clinical research without additional large RCTs providing more robust evidence. At the present, the drug should not be used except for investigational purposes.

scholarly journals Energy and caloric restriction, and fasting and cancer: a narrative review

2020 ◽  
Author(s):  
Ezzeldin M. Ibrahim ◽  
Meteb H. Al-Foheidi ◽  
Mubarak M. Al-Mansour
Keyword(s):  
Cancer Biology ◽  
Current Evidence ◽  
Future Research ◽  
Dietary Interventions ◽  
Ongoing Research ◽  
Energy Deficiency ◽  
Potential Efficacy ◽  
Clinical Benefits ◽  
The Relationship ◽  
Robust Evidence

AbstractDietary interventions have a significant impact on body metabolism. The sensitivity of cancer cells to nutrient and energy deficiency is an evolving characteristic of cancer biology. Preclinical studies provided robust evidence that energy and caloric restrictions could hinder both cancer growth and progression, besides enhancing the efficacy of chemotherapy and radiation therapy. Moreover, several, albeit low-powered, clinical trials have demonstrated clinical benefits in cancer patients. Future research will inform and firmly establish the potential efficacy and safety of these dietary interventions. Here, we review the current evidence and ongoing research investigating the relationship between various dietary restriction approaches and cancer outcomes.

Minocycline: a bacteriostatic antibiotic with pleiotropic cardioprotective effects

2015 ◽  
Vol 93 (10) ◽  
pp. 863-866 ◽  
Author(s):  
Jorge A. Brenes-Salazar
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Mechanisms Of Action ◽  
Clinical Neurology ◽  
The Family ◽  
Cardioprotective Effects ◽  
Cardiac Models ◽  
Anti Inflammatory ◽  
Cardioprotective Drug

Minocycline belongs to the family of tetracyclines, which are drugs traditionally approved as antibiotics. Based on preclinical animal cardiac models and clinical neurology trials, this drug has gained special attention as a promising cardiovascular therapeutic agent given its anti-inflammatory, antiapoptotic, antioxidant, and antienzymatic properties. This review focuses on the available evidence for minocycline as a cardioprotective drug, with special attention to mechanisms of action. Ongoing cardiovascular clinical trials are briefly discussed.

scholarly journals Current evidence on chloroquine and hydroxychloroquine and their role in the treatment and prevention of COVID-19

2020 ◽  
Author(s):  
Rephaim Mpofu ◽  
Clifford George Banda ◽  
Hannah Gunter ◽  
Enkosi Mondleki ◽  
Gayle Tatz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Evidence ◽  
Cardiac Conduction ◽  
Current Evidence ◽  
Regulatory Agencies ◽  
Close Monitoring ◽  
Treatment And Prevention ◽  
Randomised Controlled ◽  
Meta Analyses ◽  
Robust Evidence

Although chloroquine and hydroxychloroquine have not yet been shown to be safe or effective for the treatment or prevention of COVID-19, regulatory agencies in some countries have authorised their use in Coronavirus disease 2019 (COVID-19) due to the lack of available interventions. Several large clinical trials are currently underway to investigate these agents as potential therapeutic options for COVID-19. Previous research against similar pathogens that cause severe acute respiratory syndrome and Middle East respiratory syndrome has identified chloroquine and hydroxychloroquine as possible antiviral candidates against SARS-CoV-2. Despite promising pre-clinical evidence, data have thus far failed to confirm their efficacy, and recent studies suggest potential dose-related cardiotoxicity and mortality. Close monitoring for cardiac conduction abnormalities is advised with higher-than-approved doses. Additional, robust evidence from randomised controlled trials and meta-analyses are required to make informed risk-benefit assessments. Finally, the off-label prescription of these agents should be judiciously considered, and any such use should be conducted within clinical trials, or under the Monitored Emergency Use of Unregistered and Investigational Interventions framework.

scholarly journals Current evidence on chloroquine and hydroxychloroquine and their role in the treatment and prevention of COVID-19

2020 ◽  
Author(s):  
Rephaim Mpofu ◽  
Clifford G. Banda ◽  
Hannah Gunter ◽  
Enkosi Mondleki ◽  
Gayle Tatz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Evidence ◽  
Cardiac Conduction ◽  
Current Evidence ◽  
Regulatory Agencies ◽  
Close Monitoring ◽  
Treatment And Prevention ◽  
Randomised Controlled ◽  
Meta Analyses ◽  
Robust Evidence

Although chloroquine and hydroxychloroquine have not yet been shown to be safe or effective for the treatment or prevention of COVID-19, regulatory agencies in some countries have authorised their use in Coronavirus disease 2019 (COVID-19) due to the lack of available interventions. Several large clinical trials are currently underway to investigate these agents as potential therapeutic options for COVID-19. Previous research against similar pathogens that cause severe acute respiratory syndrome and Middle East respiratory syndrome has identified chloroquine and hydroxychloroquine as possible antiviral candidates against SARS-CoV-2. Despite promising pre-clinical evidence, data have thus far failed to confirm their efficacy, and recent studies suggest potential dose-related cardiotoxicity and mortality. Close monitoring for cardiac conduction abnormalities is advised with higher-than-approved doses. Additional, robust evidence from randomised controlled trials and meta-analyses are required to make informed risk-benefit assessments. Finally, the off-label prescription of these agents should be judiciously considered, and any such use should be conducted within clinical trials, or under the Monitored Emergency Use of Unregistered and Investigational Interventions framework.

scholarly journals Marine-Derived Anticancer Agents: Clinical Benefits, Innovative Mechanisms, and New Targets

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 329 ◽  
Author(s):  
Renato B. Pereira ◽  
Nikolai M. Evdokimov ◽  
Florence Lefranc ◽  
Patrícia Valentão ◽  
Alexander Kornienko ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Molecular Targets ◽  
Mechanisms Of Action ◽  
Late Development ◽  
Clinical Benefits ◽  
Approved Drugs ◽  
Current Paradigm

The role of the marine environment in the development of anticancer drugs has been widely reviewed, particularly in recent years. However, the innovation in terms of clinical benefits has not been duly emphasized, although there are important breakthroughs associated with the use of marine-derived anticancer agents that have altered the current paradigm in chemotherapy. In addition, the discovery and development of marine drugs has been extremely rewarding with significant scientific gains, such as the discovery of new anticancer mechanisms of action as well as novel molecular targets. Approximately 50 years since the approval of cytarabine, the marine-derived anticancer pharmaceutical pipeline includes four approved drugs and eighteen agents in clinical trials, six of which are in late development. Thus, the dynamic pharmaceutical pipeline consisting of approved and developmental marine-derived anticancer agents offers new hopes and new tools in the treatment of patients afflicted with previously intractable types of cancer.

Early Treatment in Migraine: How Strong is the Current Evidence?

Cephalalgia ◽  
2008 ◽  
Vol 28 (2_suppl) ◽  
pp. 28-35 ◽  
Author(s):  
A Gendolla
Keyword(s):  
Clinical Trials ◽  
Early Treatment ◽  
Early Stage ◽  
Treatment Strategies ◽  
Moderate Intensity ◽  
Current Evidence ◽  
Migraine Treatment ◽  
Migraine Pain ◽  
Clinical Benefits ◽  
Potential Risks

Over the last 10 years, triptans (serotonin 5-HT1B/1D receptor agonists) have proved to be efficacious in treating migraine pain. However, recent evidence suggests that patients are still not receiving optimal pain management, particularly in clinical trials, where triptan treatment is generally not initiated until pain has reached moderate intensity. Pathophysiological evidence indicates that if treatment is initiated at an early stage, while pain is still mild and before the onset of central sensitization, outcomes for patients may be improved. In addition, a small number of clinical trials have been reported in which triptans were taken early (within 1 h of pain onset) or while pain was still mild; although constraints of trial design and data analysis limit definite conclusions, overall the results suggest that this early/mild approach results in more rapid and sustained pain relief. New studies are therefore needed to clarify the clinical benefits of early treatment, whilst taking into account potential risks, such as medication overuse. Ultimately, migraine treatment strategies require optimization in order to meet patient expectations and to reduce the current burden of migraine-associated disability.

scholarly journals Open Questions for Harnessing Autophagy-Modulating Drugs in the SARS-CoV-2 War

2020 ◽  
Author(s):  
Patrick Brest ◽  
Jonathan Benzaquen ◽  
Daniel J. Klionsky ◽  
Paul Hofman ◽  
Baharia Mograbi
Keyword(s):  
Clinical Trials ◽  
Mechanism Of Action ◽  
Scientific Community ◽  
Cellular Mechanism ◽  
Therapeutic Options ◽  
Open Questions ◽  
The World ◽  
Pros And Cons ◽  
Anti Inflammatory

At a time when the world faces an emotional breakdown, crushing our dreams if not taking our lives, we realize that together we must fight the war against the COVID-19 outbreak even if almost the majority of the scientific community finds itself confined to home. Every day, like everyone else, we, scientists, listen to the latest news with its promises and announcements. Across the world, a surge of clinical trials trying to cure or slow down the coronavirus pandemic has been launched to bring hope instead of fear and despair. One of the most recent has drawn worldwide hype to the possible benefit of chloroquine (CQ), a well-known and broadly used anti-malarial drug, in the treatment of patients infected by the recently emerged deadly coronavirus (SARS-CoV-2). We should consider this information in the light of the long-standing anti-inflammatory and anti-viral properties of CQ-related drugs. Yet, none of these articles evoked a possible molecular or cellular mechanism of action that could account for any efficacy. Here, given the interaction of viruses with macroautophagy (hereafter referred to as autophagy), a CQ-sensitive anti-viral safeguard pathway, we would like to discuss some pros and cons concerning the current therapeutic options targeting this process.

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.

scholarly journals Current evidence on chloroquine and hydroxychloroquine and their role in the treatment and prevention of COVID-19

2020 ◽  
Author(s):  
Rephaim Mpofu ◽  
Clifford G. Banda ◽  
Hannah Gunter ◽  
Enkosi Mondleki ◽  
Gayle Tatz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Evidence ◽  
Cardiac Conduction ◽  
Current Evidence ◽  
Regulatory Agencies ◽  
Close Monitoring ◽  
Treatment And Prevention ◽  
Randomised Controlled ◽  
Meta Analyses ◽  
Robust Evidence

Although chloroquine and hydroxychloroquine have not yet been shown to be safe or effective for the treatment or prevention of COVID-19, regulatory agencies in some countries have authorised their use in Coronavirus disease 2019 (COVID-19) due to the lack of available interventions. Several large clinical trials are currently underway to investigate these agents as potential therapeutic options for COVID-19. Previous research against similar pathogens that cause severe acute respiratory syndrome and Middle East respiratory syndrome has identified chloroquine and hydroxychloroquine as possible antiviral candidates against SARS-CoV-2. Despite promising pre-clinical evidence, data have thus far failed to confirm their efficacy, and recent studies suggest potential dose-related cardiotoxicity and mortality. Close monitoring for cardiac conduction abnormalities is advised with higher-than-approved doses. Additional, robust evidence from randomised controlled trials and meta-analyses are required to make informed risk-benefit assessments. Finally, the off-label prescription of these agents should be judiciously considered, and any such use should be conducted within clinical trials, or under the Monitored Emergency Use of Unregistered and Investigational Interventions framework.

The Problem of Alternative Monotheisms: Another Serious Challenge to Theism

2018 ◽  
Vol 10 (1) ◽  
pp. 31-51
Author(s):  
Raphael Lataster
Keyword(s):  
Infinite Number ◽  
Current Evidence ◽  
God Concept ◽  
Classical Theism ◽  
The World ◽  
Divine Transcendence ◽  
Hiddenness Of God

Theistic and analytic philosophers of religion typically privilege classical theism by ignoring or underestimating the great threat of alternative monotheisms.[1] In this article we discuss numerous god-models, such as those involving weak, stupid, evil, morally indifferent, and non-revelatory gods. We find that theistic philosophers have not successfully eliminated these and other possibilities, or argued for their relative improbability. In fact, based on current evidence – especially concerning the hiddenness of God and the gratuitous evils in the world – many of these hypotheses appear to be more probable than theism. Also considering the – arguably infinite – number of alternative monotheisms, the inescapable conclusion is that theism is a very improbable god-concept, even when it is assumed that one and only one transcendent god exists.[1] I take ‘theism’ to mean ‘classical theism’, which is but one of many possible monotheisms. Avoiding much of the discussion around classical theism, I wish to focus on the challenges in arguing for theism over monotheistic alternatives. I consider theism and alternative monotheisms as entailing the notion of divine transcendence.

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