Use Of Hydroxychloroquine In Treatment Research Articles

Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial

BackgroundPrevious Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers.MethodsWe conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540.FindingsFrom May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52–1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53–1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57–1·04]).InterpretationIn outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting.FundingCOALITION COVID-19 Brazil and EMS.

Rise and Fall: Hydroxychloroquine and COVID-19 Global Trends: Interest, Political Influence, and Potential Implications.

ObjectiveThe coronavirus disease 2019 (COVID‐19) pandemic has led to rapid research and reporting on potential preventatives and treatments for the disease, including the drug hydroxychloroquine (HCQ). Despite a lack of robust evidence to support the use of HCQ for treatment of COVID‐19, it was publicly endorsed and received widespread media coverage and public interest. The purpose of this report is to describe and contextualize the surges in public interest, demand, and adoption of HCQ for treatment of COVID‐19 and outline implications for future public health policy and practice.MethodsUsing national and global events and Google Trends data as a measure of public interest, we describe the timeline and trends in the emergence of, interest in, and adoption of HCQ as a treatment of COVID‐19. We additionally review reports on public demand for HCQ for treatment of COVID‐19 and impacts on medication access among patients with indicated uses.ResultsPublic interest and demand for HCQ surged in the United States and globally following endorsements from public officials and enaction of policies to facilitate off‐label use of HCQ for treatment of COVID‐19. Surges in demand for HCQ led to multiple documented shortages and barriers to accessing HCQ treatment for patients with indicated uses for HCQ. Although there have been reversals in policies to support HCQ use for treatment of COVID‐19 in some regions, others have continued or expanded recommended uses.ConclusionInsights from the global response to HCQ and COVID‐19 can be used to inform prudent decision‐making in the future to prevent premature action and promote informed and equitable responses to promote public health.

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19

Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. ClinicalTrials.gov: NCT04332991.

Swinging the pendulum: lessons learned from public discourse concerning hydroxychloroquine and COVID-19

ABSTRACT Introduction Several months into the COVID-19 pandemic, safe and effective treatments against this global health disaster have yet to be identified. Clinical research trials around the world are underway testing a wide array of possible medications. In particular, the off-label use of hydroxychloroquine for COVID-19 prophylaxis and treatment has created many unprecedented challenges for the scientific community and the public. Areas covered We critically assessed major events from February – May 2020 that contributed to widespread use of hydroxychloroquine for the treatment and prophylaxis of COVID-19. We aimed to explore how opinions toward hydroxychloroquine may shift from early enthusiasm (based on in vitro and preliminary clinical data) to the hope for a miracle cure (through communication and promotion of questionable results) and, finally, to a rise of skepticism as more in-depth analyses are emerging. Expert opinion Mindful and rigorous acquisition of data, as well as its interpretation, are essential to an effective pandemic response. The rapid and premature promotion of results has had major implications for global crisis management, even creating distrust among the public. It is crucial for the medical and scientific community to incorporate the lessons learned from this situation.

Does pandemic justify the use of hydroxychloroquine for treatment and prevention of COVID-19 in India?

The Indian Council of Medical Research (ICMR), recommended the use of hydroxychloroquine (HCQ) as a prophylactic against COVID-19 among health care workers and asymptomatic contacts of laboratory confirmed cases of COVID. This is widely criticised as a hastily taken step with political inclination and minimal evidence backing. In the current scenario, where there is mass fear against COVID-19, this recommendation has made the people to believe that it will kill the viruses. This has important public health implications which are discussed below. Better communication should have been planned to ensure everyone does not go out and buy it. However, as a nation of 1.3 billion, we need to capitalize on this opportunity to generate data and valuable evidence on the use of HCQ to beat this pandemic. All health care workers taking this drug should volunteer themselves to be part of a trial/observational study and get registered online to generate useful data related to its safety and efficacy and guide future recommendations. The other risk group which includes asymptomatic contacts of laboratory confirmed COVID-19 patients are under surveillance by the state and local health authorities and could also be roped into this study to generate robust evidence. Of course, pandemic does not just justify the use of HCQ, but pandemic is the time to innovate, think out of box and generate evidence to prove the same so that we can lives. This article is protected by copyright. All rights reserved.

Response to “Quantitative Clinical Pharmacology INPUT to SARS‐CoV‐2 Therapeutics Should be Based on Robust Data”

We appreciate the response to our timely analysis and would like to address Dr. Standing's comments. As of today, there are more than 110 clinical trials registered on clinicaltrials.gov evaluating hydroxychloroquine (HCQ) efficacy for coronavirus disease 2019 (COVID-19). The common problem for all these studies is what is the optimal dosing regimen and what is the safety associated with said regimen in COVID-19 patients. Our goal was to synthesize all emerging data in real time using state-of-the-art model-based tools and to provide the community with a quantitative assessment of various HCQ regimens. As in any model-based analysis, assumptions are inevitable, and all the major ones are listed in our paper. Here we address the comments from Dr. Standing. As opposed to using actual polymerase chain reaction cycle threshold, we modeled a transformed value, more representative of viral load. While the function we used is indeed nonlinear, the relationship over our studied range appears to be linear (R2 = 0.97). Data transformations using various functions are commonly employed in statistical analysis, do not alter the raw data, should not affect the parameter estimates, and improve the interpretability of our results.1 We agree with Dr. Standing: We currently do not have sufficient data to estimate a separate treatment and immune effect on viral load. However, this is true for many other infectious diseases.2 The world is still learning the natural history of COVID-19, including the immune response and viral-shedding dynamics. We observed that the drug effect alone is not sufficient to clear the virus. Additional (most likely) immune-dependent killing occurs, which we described by a separate function. Our sensitivity analysis illustrates how these assumptions might affect viral load trajectories and treatment efficacy (Figure 7). Literature reports a 24-fold difference in in vitro concentration of drug producing 50% of maximum effect (EC50).3-5 Our main question was whether better viral control could be achieved with higher doses (Figure 2). During this process, we identified the 48-hour EC50 from Yao et al. as an outlier (Figure 4) and elected to base our dosing simulations on the predicted clinical EC50, which aligned with the majority of EC50s reported. Only randomized controlled trials can offer definitive answers on the use of HCQ for treatment of COVID-19. We predict a lack of clinical efficacy at the currently studied/used doses due to insufficient drug exposure. While higher HCQ doses may be needed to achieve therapeutic benefit, significant safety concerns exist, indicating that HCQ’s therapeutic margin is likely very narrow. No funding was received for this work. All authors declared no competing interests for this work.

Hydroxychloroquine for COVID-19: A review and a debate based on available clinical trials/case studies

Hydroxychloroquine (HCQ) as a drug grabbed serious attention of whole world in dealing with COVID-19 pandemic. Recently some in-vitro and in-vivo study showing possible inhibition of SARS-CoV-2 by use of HCQ. However at the same time, some case studies showing NO clinical benefit/ poor clinical outcome with substantial detrimental adverse effects by use of HCQ in treatment of coronavirus disease-2019. Thus, the HCQ use (in COVID-19 treatment) is of current international interest, although a consensus has not yet been reached. More evidences are still required to prove efficacy of HCQ against COVID-19. In view of this, the present review highlights the current ongoing research related to use of HCQ in treatment coronavirus disease-2019. The present review will discuss the possible anti-viral mechanism of HCQ, prophylaxis strategy and effect of HCQ against SARS-CoV-2 virus in-vitro study. Further this review also summarizes and debates all available clinical trials/ case studies of HCQ use against COVID-19 (with clinical outcome). Finally possible detrimental adverse effects are also discussed considering the public health and pharmacovigilance concern.
 Keywords: Potency of hydroxychloroquine; COVID-19; Coronavirus disease-2019; Clinical trials; SARS-CoV-2; Adverse effects of hydroxychloroquine; Pharmacovigilance concern

Ocular Manifestations of Rheumatoid Arthritis and Complications of Hydroxychloroquine Treatment

Background: Rheumatoid arthritis (RA) is the most common autoimmune disease. Ocular manifestations of RA vary and are mainly keratoconjunctivitis sicca, episcleritis, scleritis and keratitis. Antimalarial drugs [hydroxychloroquine (HCQ) and chloroquine (CQ)] have been used for the treatment of RA. Objective: The aim of this study was to study the ocular manifestations of rheumatoid arthritis and the complications of the use of hydroxychloroquine in treatment. Patients and methods: A prospective study that was conducted at Al-Zahraa University Hospital. The study included a total of 80 eyes of 40 patients. Patients were divided into two groups: Group (1) 20 RA patients not using HCQ treatment and group (2) 20 RA patients using HCQ treatment. All patients underwent complete ophthalmic examination including SD-OCT. Results: the most ocular manifestations found in patients were keratoconjunctivitis sicca (KCS) 93.8%, scleritis and episcleritis 2.5%, acute anterior uveitis (AAU) and sclerosing keratitis 1.3%. Regarding SD-OCT finding comparing between the two groups, we found signs of early HCQ retinopathy in patients of group 2 in the form of parafoveal and perifoveal thining compared to group 1. Conclusion: RA is associated with many extra-articular manifestations, HCQ and CQ used in treatment of RA have significant efficacy and safety, but with long duration of using can cause retinopathy, and follow up of patients is necessary to detect early retinopathy.