Network meta‐analysis of post‐exposure prophylaxis randomized clinical trials

BACKGROUND Hydroxychloroquine (HCQ) is an anti-malarial and immunomodulatory drug considered a potential candidate for drug repurposing in COVID-19 due to their in vitro antiviral activity against SARS-CoV-2. Despite the potential antiviral effects and anti-inflammatory profile, the results based on clinical studies are contradictory and the quality of the decision-making process from meta-analyses summarizing the available evidence selecting studies with different designs and unblinded trials is limited. The aim of this study was to synthesize the best evidence on the efficacy and safety of HCQ as pre-and post-exposure prophylaxis and treatment of non-hospitalized and hospitalized patients with COVID-19. METHODS Searches for studies were performed in PubMed, Web of Science, Embase, Lilacs, the website ClinicalTrials.gov and the preprint server medRxiv from January 1, 2020 to May 17, 2021. The following elements were used to define eligibility criteria: (1) Population, individuals at high-risk of exposure to SARS-CoV-2 (pre-exposure), individuals who had close contact with a positive or probable case of COVID-19 (post-exposure), non-hospitalized patients with COVID-19 and hospitalized patients with COVID-19; (2) Intervention, HCQ; (3) Comparison, placebo; (4) Outcomes: incidence of SARS-CoV-2 infection, need for hospitalization, length of hospital stay, need for invasive mechanical ventilation (MV), death, and adverse events; and (5) Study type, blinded, placebo-controlled, randomized clinical trials (RCTs). Risk of bias was judged according to the Cochrane guidelines for RCTs. Treatment effects were reported as relative risk (RR) for dichotomous variables and mean difference (MD) for continuous variables with 95% confidence intervals (CI). We used either a fixed or random-effects model to pool the results of individual studies depending on the presence of heterogeneity. The GRADE system was used to evaluate the strength of evidence between use of HCQ and the outcomes of interest. RESULTS Fourteen blinded, placebo-controlled RCTs were included in the meta-analysis. Four trials used HCQ as a prophylactic medication pre-exposure to COVID-19, two as a prophylactic medication post-exposure to COVID-19, three as treatment for non-hospitalized patients, and five as treatment for hospitalized patients with COVID-19. We found no decreased risk of SARS-CoV-2 infection among individuals receiving HCQ as pre-exposure (RR = 0.90; 95% CI 0.46 to 1.77) or post-exposure (RR = 0.96; 95% CI 0.72 to 1.29) prophylaxis to prevent COVID-19. There is no decreased risk of hospitalization for outpatients with SARS-CoV-2 infection (RR = 0.64; 95% CI 0.33 to 1.23) and no decreased risk of MV (RR = 0.81; 95% CI 0.49 to 1.34) and death (RR = 1.05; 95% CI 0.62 to 1.78) among hospitalized patients with COVID-19 receiving HCQ. The certainty of the results on the lack of clinical benefit for HCQ was rated as moderate. Moreover, our results demonstrated an increased risk for any adverse events and gastrointestinal symptoms among those using HCQ. CONCLUSION Available evidence based on the results of blinded, placebo-controlled RCTs showed no clinical benefits of HCQ as pre-and post-exposure prophylaxis and treatment of non-hospitalized and hospitalized patients with COVID-19.

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Post-exposure prophylaxis vaccination rate and risk factors of human rabies in mainland China: a meta-analysis

Epidemiology and Infection ◽

10.1017/s0950268818003175 ◽

2018 ◽

Vol 147 ◽

Author(s):

D. L. Wang ◽

X. F. Zhang ◽

H. Jin ◽

X. Q. Cheng ◽

C. X. Duan ◽

...

Keyword(s):

Risk Factors ◽

Rural Areas ◽

Meta Analysis ◽

Mainland China ◽

Vaccination Rate ◽

Human Rabies ◽

Post Exposure Prophylaxis ◽

Eastern Region ◽

Post Exposure ◽

Exposure Prophylaxis

AbstractRabies is one of the major public health problems in China, and the mortality rate of rabies remains the highest among all notifiable infectious diseases. A meta-analysis was conducted to investigate the post-exposure prophylaxis (PEP) vaccination rate and risk factors for human rabies in mainland China. The PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical and Wanfang databases were searched for articles on rabies vaccination status (published between 2007 and 2017). In total, 10 174 human rabies cases from 136 studies were included in this meta-analysis. Approximately 97.2% (95% confidence interval (CI) 95.1–98.7%) of rabies cases occurred in rural areas and 72.6% (95% CI 70.0–75.1%) occurred in farmers. Overall, the vaccination rate in the reported human rabies cases was 15.4% (95% CI 13.7–17.4%). However, among vaccinated individuals, 85.5% (95% CI 79.8%–83.4%) did not complete the vaccination regimen. In a subgroup analysis, the PEP vaccination rate in the eastern region (18.8%, 95% CI 15.9–22.1%) was higher than that in the western region (13.3%, 95% CI 11.1–15.8%) and this rate decreased after 2007. Approximately 68.9% (95% CI 63.6–73.8%) of rabies cases experienced category-III exposures, but their PEP vaccination rate was 27.0% (95% CI 14.4–44.9%) and only 6.1% (95% CI 4.4–8.4%) received rabies immunoglobulin. Together, these results suggested that the PEP vaccination rate among human rabies cases was low in mainland China. Therefore, standardised treatment and vaccination programs of dog bites need to be further strengthened, particularly in rural areas.

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Three-day regimen of oseltamivir for post-exposure prophylaxis of influenza in hospital wards: a study protocol for a prospective, multi-center, single-arm trial

BMC Infectious Diseases ◽

10.1186/s12879-021-06602-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Nobuhisa Ishiguro ◽

Yoichi M. Ito ◽

Sumio Iwasaki ◽

Miki Nagao ◽

Hideki Kawamura ◽

...

Keyword(s):

Clinical Trials ◽

University Hospital ◽

Infection Prevention And Control ◽

Post Exposure Prophylaxis ◽

University Hospitals ◽

Once Daily ◽

Post Exposure ◽

Link Type ◽

Exposure Prophylaxis ◽

Close Contacts

Abstract Background In a previous retrospective observational study, a 3-day regimen of oseltamivir as post-exposure prophylaxis (PEP) for preventing transmission of influenza in wards was shown to be comparable to 7- to 10-day regimens provided index cases were immediately separated from close contacts. In order to confirm the efficacy of a 3-day regimen, we started to conduct a prospective, multi-center, single-arm trial. Methods This study is a prospective, multi-center, single-arm study designed by the Sectional Meeting of Clinical Study, Japan Infection Prevention and Control Conference for National and Public University Hospitals. Index patients with influenza are prescribed a neuraminidase inhibitor and are discharged immediately or transferred to isolation rooms. The close contacts are given oseltamivir as 75 mg capsules once daily for adults or 2 mg/kg (maximum of 75 mg) once daily for children for 3 days as PEP. All close contacts are monitored for development of influenza for 7 days after starting PEP. Discussion A 3-day regimen of oseltamivir as PEP has advantages over 7- to 10-day regimens in terms of costs, medication adherence and adverse effects. Trial registration The Institutional Review Board of Hokkaido University Hospital for Clinical Research, 015-0518, registered on November 11, 2016. UMIN Clinical Trials Registry, UMIN000024458, disclosed on October 31, 2016. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027881. Japan Registry of Clinical Trials, jRCTs011180015, disclosed on March 14, 2019. https://jrct.niph.go.jp/latest-detail/jRCTs011180015

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Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis

10.1101/2020.09.30.20204693 ◽

2020 ◽

Author(s):

Joseph A. Ladapo ◽

John E. McKinnon ◽

Peter A. McCullough ◽

Harvey Risch

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Side Effects ◽

Fixed Effects ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Randomized Controlled ◽

Exposure Prophylaxis

Objective--To determine if hydroxychloroquine (HCQ) reduces the incidence of new illness, hospitalization or death among outpatients at risk for or infected with SARS-CoV-2 (COVID-19). Design--Systematic review and meta-analysis of randomized clinical trials. Data sources--Search of MEDLINE, EMBASE, PubMed, medRxiv, PROSPERO, and the Cochrane Central Register of Controlled Trials. Also review of reference lists from recent meta-analyses. Study selection--Randomized clinical trials in which participants were treated with HCQ or placebo/standard-of-care for pre-exposure prophylaxis, post-exposure prophylaxis, or outpatient therapy for COVID-19. Methods--Two investigators independently extracted data on trial design and outcomes. Medication side effects and adverse reactions were also assessed. The primary outcome was COVID-19 hospitalization or death. When unavailable, new COVID-19 infection was used. We calculated random effects meta-analysis according to the method of DerSimonian and Laird. Heterogeneity between the studies was evaluated by calculation of Cochran Q and I2 parameters. An Egger funnel plot was drawn to investigate publication bias. We also calculated the fixed effects meta-analysis summary of the five studies. All calculations were done in Excel, and results were considered to be statistically significant at a two-sided threshold of P=.05. Results--Five randomized controlled clinical trials enrolling 5,577 patients were included. HCQ was associated with a 24% reduction in COVID-19 infection, hospitalization or death, P=.025 (RR, 0.76 [95% CI, 0.59 to 0.97]). No serious adverse cardiac events were reported. The most common side effects were gastrointestinal. Conclusion--Hydroxychloroquine use in outpatients reduces the incidence of the composite outcome of COVID-19 infection, hospitalization, and death. Serious adverse events were not reported and cardiac arrhythmia was rare. Systematic review registration--This review was not registered.

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Repurposed prophylaxis strategies for COVID-19: a review

10.1101/2020.05.30.20117937 ◽

2020 ◽

Author(s):

Erwan Sallard ◽

François-Xavier Lescure ◽

Charles Burdet ◽

Jérémie Guedj ◽

Yazdan Yazdanpanah ◽

...

Keyword(s):

At Risk ◽

Clinical Trials ◽

Therapeutic Strategies ◽

Bcg Vaccine ◽

Post Exposure Prophylaxis ◽

Post Exposure ◽

Exposure Prophylaxis

AbstractIntroductionEfficient therapeutic strategies are needed to counter the COVID-19 pandemic, caused by the SARSCoV-2 virus. In a context where specific vaccines are not yet available, the containment of the pandemic would be facilitated with efficient prophylaxis.MethodsWe screened several clinical trials repositories and platforms in search of the prophylactic strategies that are investigated against COVID-19 in late April 2020.ResultsUp to April 27, 2020, we found 68 clinical trials targeting medical workers (n = 43, 63%), patients relatives (n = 16, 24%) or individuals at risk of severe COVID-19 (n = 5, 7%). (Hydroxy)chloroquine was the most frequently evaluated treatment (n = 46, 68%), before BCG vaccine (n = 5, 7%). Sixty-one (90%) clinical trials were randomized with a median of planned inclusions of 600 (IQR 255–1515).ConclusionThe investigated prophylaxis strategies cover both pre- and post-exposure prophylaxis and study numerous immune enhancers and antivirals, although most research efforts are focused on (hydroxy)chloroquine.

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Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19

10.1101/2020.07.16.20155531 ◽

2020 ◽

Cited By ~ 4

Author(s):

SARAH M LOFGREN ◽

Melanie R Nicol ◽

Ananta S Bangdiwala ◽

Katelyn A Pastick ◽

Elizabeth C Okafor ◽

...

Keyword(s):

Clinical Trials ◽

Side Effects ◽

Side Effect ◽

Randomized Clinical Trials ◽

Safety Data ◽

Post Exposure Prophylaxis ◽

Serious Adverse Events ◽

Double Blind ◽

Gastrointestinal Side Effects ◽

Exposure Prophylaxis

Introduction: Use of hydroxychloroquine in hospitalized patients with COVID-19, especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from three outpatient randomized clinical trials. Methods: We conducted three randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, post-exposure prophylaxis and early treatment for COVID-19. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings. Results: We enrolled 2,795 participants. The median age of research participants was 40 (IQR 34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2,324 (84%) participants reported side effect data, and 638 (27%) reported at least one medication side effect. Side effects were reported in 29% with daily, 36% with twice weekly, 31% with once weekly hydroxychloroquine compared to 19% with placebo. The most common side effects were upset stomach or nausea (25% with daily, 18% with twice weekly, 16% with weekly, vs. 10% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for daily, 16% twice weekly, 12% weekly, vs. 6% for placebo). Two individuals were hospitalized for atrial arrhythmias, one on placebo and one on twice weekly hydroxychloroquine. No sudden deaths occurred. Conclusion: Data from three outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials can safely investigate whether hydroxychloroquine is efficacious for COVID-19.

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Awareness and Use of Post-exposure Prophylaxis for HIV Prevention Among Men Who Have Sex With Men: A Systematic Review and Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.783626 ◽

2022 ◽

Vol 8 ◽

Author(s):

Junyan Jin ◽

Runsong Sun ◽

Tingting Mu ◽

Taiyi Jiang ◽

Lili Dai ◽

...

Keyword(s):

Systematic Review ◽

Hiv Prevention ◽

Meta Analysis ◽

Post Exposure Prophylaxis ◽

Structural Barriers ◽

Post Exposure ◽

At Risk Populations ◽

Sex With Men ◽

Exposure Prophylaxis ◽

Over Time

Background: The use of post-exposure prophylaxis (PEP) is effective in reducing HIV risk, but it is underused by men who have sex with men (MSM) due to certain psychological and sociostructural factors. This article assessed the awareness and use of PEP among MSM in an effort to increase the visibility and uptake of PEP among at-risk populations.Methods: We conducted a systematic literature search of the PubMed, Web of Science, PsycINFO, and Google Scholar electronic databases. Studies were screened for inclusion, and relevant data were abstracted, assessed for bias, and synthesized. Pooled effect estimates were calculated using random effects meta-analysis, meta-regression and subgroup analysis, and a qualitative review and risk of bias assessment were performed (PROSPERO, CRD42019123815).Results: Twenty eligible studies involving 12,579 MSM were included in the meta-analysis. The pooled estimate of the proportions of MSM who were aware of PEP was modest at 59.9% (95% CI: 50.5~68.7) and that of MSM who previously used PEP was very low at 4.9% (95% CI: 2.4~9.8). PEP awareness showed no clear change over time, while PEP use significantly changed over time. Multiple factors affected awareness, including educational attainment, race/ethnicity, levels of HIV stigma, access to condoms, and so on. Many factors could potentially impede or facilitate the use of PEP, such as income, lack of PEP information, and partnership.Conclusion: We observed that PEP is an underused HIV prevention strategy among MSM and that once MSM become aware of PEP, the majority are willing to use it if they are supported appropriately in terms of a range of individual, social, and structural barriers.Systematic Review Registration: http://www.cdr.york.ac.uk/prospero, PROSPERO [CRD42019123815].

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