Efficacy of chloroquine and hydroxychloroquine for the treatment of hospitalized COVID-19 patients: a meta-analysis.
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ABSTRACT:
SUBMITTER: Deng J
PROVIDER: S-EPMC8647998 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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Efficacy of chloroquine and hydroxychloroquine for the treatment of hospitalized COVID-19 patients: a meta-analysis.
Deng Jiawen J Zhou Fangwen F Heybati Kiyan K Ali Saif S Zuo Qi Kang QK Hou Wenteng W Dhivagaran Thanansayan T Ramaraju Harikrishnaa Ba HB Chang Oswin O Wong Chi Yi CY Silver Zachary Z
Future virology 20211101
<b>Aims:</b> To evaluate the efficacy and safety of hydroxychloroquine/chloroquine, with or without azithromycin, in treating hospitalized COVID-19 patients. <b>Materials & methods:</b> Data from randomized and observational studies were included in a random-effects meta-analysis. Primary outcomes included time to negative conversion of SARS-CoV-2 tests, length of stay, mortality, incidence of mechanical ventilation, time to normalization of body temperature, incidence of adverse events and inci ...[more]
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Project description:BackgroundResults from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients.MethodsWe searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions.ResultsEight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively).ConclusionsThe findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.
| S-EPMC9521809 | biostudies-literature
Project description:ImportanceResults from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data (IPD), including unanalyzed data from trials terminated early, enables further investigation of the efficacy and safety of HCQ/CQ.ObjectiveTo assess efficacy of HCQ/CQ in patients hospitalized with COVID-19, both overall and in prespecified subgroups.Data sourcesClinicalTrials.gov was searched multiple times in May-June 2020. Principal investigators of US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients were invited to collaborate in this IPD meta-analysis.Study selectionRCTs in which: (1) HCQ/CQ was a treatment arm; (2) patient informed consent and/or individual study IRB approval allowed for data sharing; (3) principal investigators/their institutions signed a data use agreement for the present study; and (4) the outcomes defined in this study were recorded or could be extrapolated.Data extraction and synthesisWherever possible, harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator, then shared via a secure online data sharing platform to create a pooled data set. When this was not possible, individual study data were harmonized and merged manually. Data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions.Main outcomes and measures7-point ordinal scale, measured between day 28 and 35 post-enrollment.ResultsEight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We found no evidence of a difference in ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively).Conclusions and relevanceThe findings of this IPD meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.Key pointsQuestion: Does hydroxychloroquine/chloroquine benefit hospitalized patients with COVID-19, overall or within prespecified subgroups?Findings: In this individual participant data meta-analysis of 770 hospitalized COVID-19 patients across 8 clinical trials, we did not find evidence of a benefit of hydroxychloroquine/chloroquine, measured by a 7-point ordinal COVID-19 severity score at 28-35 days post-enrollment, in the pooled study population. We also found no substantial treatment effect heterogeneity among prespecified patient subgroups.Meaning: This study supports the consensus that hydroxychloroquine/chloroquine should not be used to treat hospitalized patients with COVID-19.
| S-EPMC8764733 | biostudies-literature
Project description:ObjectivesClinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients.MethodsWe searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, ICU admission/mechanical ventilation and hospitalization.ResultsSeven randomized clinical trials (RCTs) and 14 cohort studies were included (20 979 patients). Thirteen studies (1 RCT and 12 cohort studies) with 15 938 hospitalized patients examined the effect of HCQ on short-term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96-1.15, I2 = 0%). Six cohort studies examined the effect of the HCQ+azithromycin combination with a pooled adjusted OR of 1.32 (95% CI 1.00-1.75, I2 = 68.1%). Two cohort studies and four RCTs found no effect of HCQ on viral clearance. One small RCT demonstrated improved viral clearance with CQ and HCQ. Three cohort studies found that HCQ had no significant effect on mechanical ventilation/ICU admission. Two RCTs found no effect for HCQ on hospitalization risk in outpatients with COVID-19.ConclusionsModerate certainty evidence suggests that HCQ, with or without azithromycin, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19.
| S-EPMC7665543 | biostudies-literature
Project description:Repurposed drugs like hydroxycloroquine (HCQ) and chloroquine (CQ) are being tested for potential therapeutic role in COVID-19. We aimed to evaluate efficacy and safety of HCQ and CQ in COVID-19. Using PubMed, EMBASE, medRxiv, Google Scholar, clinicaltrials.gov, electronic search was carried out to identify relevant articles till June 2020 with re-evaluation in last week of November 2020. Observational and interventional clinical studies comparing efficacy of CQ or HCQ to standard management or other drug/s for SARS-CoV-2 infection patients were included. Cochrane review manager version 5.3 was used for synthesis of meta-analysis results. For randomized controlled trials, risk of bias was assessed using Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB-2). ROBINS-I was used for quality assessment of observational studies. Overall evidence quality generated by review was graded as per GRADE Recommendation. A total of 903 studies were screened. Nineteen studies were included in synthesis of meta-analysis with total of 4,693, 1,626, and 6,491 patients in HCQ/CQ, HCQ/CQ + AZ and control groups, respectively. HCQ/CQ treatment was associated with significantly increased rates of virological cure (OR = 2.08, 95%CI = 1.36-3.17; P = 0.0007) and radiological cure (OR = 3.89, 95%CI = 1.35 - 11.23; P = 0.01) compared to control. HCQ/CQ had no difference in unadjusted mortality rate (unadjusted OR = 0.98 95% CI = 0.70-1.37, P = 0.89, random effect model) and adjusted hazard ratio for mortality (adjusted HR = 1.05, 95%CI = 0.86--1.29; P = 0.64). However, a significant increase in odds of disease progression (OR = 1.77, 95%CI = 1.46-2.13; P < 0.00001) and QT prolongation (OR = 11.15, 95%CI = 3.95-31.44; P < 0.00001) was noted. The results with HCQ/CQ and azithromycin combination were similar to HCQ/CQ mono-therapy. In the light of contemporary evidence on effectiveness of HCQ/CQ, judicious and monitored use of HCQ/CQ for treatment of COVID-19 patients is recommended in low to middle income countries with emphasis on no mortality benefit. Registration number of Systematic review. Register in PROSPERO database: cRD42020187710.
| S-EPMC8284216 | biostudies-literature
Project description:We systematically reviewed the efficacy and safety of hydroxychloroquine as treatment for hospitalized COVID-19. Randomized controlled trials (RCTs) evaluating hydroxychloroquine as treatment for hospitalized COVID-19 patients were searched until 2nd of December 2020. Primary outcomes were all-cause mortality, need of mechanical ventilation, need of non-invasive ventilation, ICU admission and oxygen support at 14 and 30 days. Secondary outcomes were clinical recovery and worsening, discharge, radiological progression of pneumonia, virologic clearance, serious adverse events (SAE) and adverse events. Inverse variance random effects meta-analyses were performed. Thirteen RCTs (n=18,540) were included. Hydroxychloroquine total doses ranged between 2000 and 12,400 mg; treatment durations were from 5 to 16 days and follow up times between 5 and 30 days. Compared to controls, hydroxychloroquine non-significantly increased mortality at 14 days (RR 1.07, 95%CI 0.92-1.25) or 30 days (RR 1.08, 95%CI 1.00-1.16). Hydroxychloroquine did not affect other primary or secondary outcomes, except SAEs that were significantly higher than the control (RR 1.24, 95%CI 1.05-1.46). Eleven RCTs had high or some concerns of bias. Subgroup analyses were consistent with main analyses. Hydroxychloroquine was not efficacious for treating hospitalized COVID-19 patients and caused more severe adverse events. Hydroxychloroquine should not be recommended as treatment for hospitalized COVID-19 patients.
| S-EPMC8201261 | biostudies-literature
Project description:The coronavirus disease 19 (COVID-19) pandemic has caused significant morbidity and mortality worldwide and an effective treatment is needed. Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown in vitro antiviral activity against SARS-CoV-2 which causes the disease, but the evidence from in vivo studies so far has been inconclusive.ObjectiveTo evaluate the efficacy and safety of CQ and HCQ in the treatment of COVID-19.Data sourcesWe systematically searched the PubMed, Embase, MEDLINE, Cochrane CENTRAL, CINAHL, Scopus, Joanna Briggs Institute Database, ClinicalTrials.gov, and Chinese Clinical Trial Registry (ChiCTR) for all articles published between 01 January 2020 to 15 September 2020 on CQ/HCQ and COVID-19 using a predefined search protocol; without any language restrictions. A search of grey literature repositories (New York Academy of Medicine Grey Literature and Open Grey), and pre-publication server deposits (medRxIV and bioRxIV) was also performed.Study selectionRandomized clinical trials (RCT) which compared CQ/HCQ to standard supportive therapy in treating COVID-19 were included.Data extraction and synthesisData were extracted from original publications by four independent reviewers. Risk of bias was assessed using the Cochrane Collaboration's assessment tool. Data were meta-analyzed using a random-effect models. Results are reported according to PRISMA guidelines. Main Outcome(s) and Measure(s): The primary prespecified efficacy outcome was all-cause mortality. The primary safety outcome was any adverse effect attributed to use of CQ/HCQ.ResultsEight RCTs were included and pooled in the mortality meta-analysis (6,592 unique participants; mean age = 59.4 years; 42% women). CQ/HCQ did not show any mortality benefit when compared to standard supportive therapy (Pooled Relative Risk [RR] 1.07; 95% CI = 0.97-1.18; I2 statistic = 0.00%). Sensitivity and sub-group analyses showed similar findings. Any adverse event was significantly higher in patients randomized to CQ/HCQ (RR = 2.51; 95% CI = 1.53-4.12; n = 1,818 patients), but the risk of developing severe adverse event was not statistically significant (RR = 0.99, 95% CI = 0.53-1.86; n = 6,456 patients).Conclusions and relevanceEvidence from currently published RCTs do not demonstrate any added benefit for the use of CQ or HCQ in the treatment of COVID-19 patients.
| S-EPMC8012280 | biostudies-literature
Project description:BackgroundThere is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain.ObjectiveWe performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19.MethodsTwo reviewers searched for published and pre-published relevant articles between December 2019 and 8 June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa Scale. The quality of evidence was graded as per the GRADE approach.ResultsWe reviewed 12 observational and 3 randomized trials which included 10,659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46], time to fever resolution (mean difference - 0.54 days (- 1.19-011)) or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes.Authors' conclusionThe available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.
| S-EPMC7471562 | biostudies-literature
Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the effects of chloroquine (CQ) and hydroxychloroquine (HCQ) as: an antiviral treatment on death and time to clearance of the virus from clinical samples and recovery in people with COVID‐19; a prophylactic treatment on prevention of COVID‐19 in people at risk of SARS‐CoV‐2 exposure; a prophylactic treatment on prevention of COVID‐19 in people who have been exposed to SARS‐CoV‐2.
| S-EPMC7177204 | biostudies-literature
Project description:IntroductionGiven the current lack of an approved and effective treatment or vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), repositioning old drugs for use as an antiviral treatment is an interesting strategy because knowledge about these drugs' safety profile, posology, and drug interactions is already known. Chloroquine and hydroxychloroquine, widely used as antimalarial and autoimmune disease drugs, have recently been reported as a potential broad-spectrum antiviral drug.BackgroundThe in vitro antiviral activity of chloroquine has been identified since the late 1960s. However, antiviral mechanisms of chloroquine remain speculative. Several clinical trials have been conducted to test the efficacy and safety of chloroquine or hydroxychloroquine in the treatment of COVID-19-associated pneumonia. The quality of the studies and the outcomes are evaluated in this systematic review and meta-analysis.Review resultsLiterature review revealed 23 clinical studies. Only 9 of 23 studies were randomized controlled trials. Of nine randomized controlled trials, only study by Skipper et al. was deemed to be at low risk of bias. All studies evaluated variedwith different outcomes. Mechanical ventilation and virological clearance were the only common outcomes evaluated in more than two studies. Virological clearance odds ratio (OR) was 1.25 (95% confidence interval [CI] of 0.57-2.73; Chi2 = 0.83; I2 = 0%). GRADE quality of evidence was downgraded by three levels to very low due to concerns about the risk of bias, inconsistency, and imprecision. For mechanical ventilation, OR was 1.09 (95% CI 0.80-1.50; Chi2 = 0; I2 = 0). GRADE quality of evidence was downgraded by two levels to low due to concerns about the risk of bias and imprecision. There was no statistically significant difference between the groups for these two outcomes.ConclusionAs per the available evidence, based on our review, we conclude that hydroxychloroquine/chloroquine has not shown to be beneficial when used for the treatment of patients with COVID-19 pneumonia.How to cite this articleShetty RM, Namachivayam A. Evidence for Chloroquine/Hydroxychloroquine in the Treatment of COVID-19. Indian J Crit Care Med 2021;25(4):441-452.
| S-EPMC8138637 | biostudies-literature
Project description: Not available
| S-EPMC8094389 | biostudies-literature