SUMMARY OBJECTIVE To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine (HCQ). METHODS The studies were selected using a combination based on the Medical Subject Headings (MeSH). The databases searched were MEDLINE (PubMed), LILACS, SciELO, and BIREME, encompassing articles from January 2010 to May 2020, with no restrictions of language and place of publication. RESULTS A total of 148 articles with the potential to be included were retrieved. Of these, two answered the research question, which consisted of seeking evidence of the ototoxic effects of hydroxychloroquine. These studies scored 11 in their quality assessment with the modified protocol by Pithon et al.13. CONCLUSIONS The studies reported possible ototoxicity of HCQ. Audiovestibular changes, such as hearing loss, peripheral vestibular syndrome, and tinnitus were evidenced in patients submitted to HCQ. The improvement in the audiological examinations and the regression in the vestibular syndrome after stopping the treatment with HCQ are strong arguments in favor of the ototoxicity caused by this medication. However, there are still divergences about the relationship between ototoxic effects and the use of HCQ.

OBJECTIVE:

To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine (HCQ).

METHODS:

The studies were selected using a combination based on the Medical Subject Headings (MeSH). The databases searched were MEDLINE (PubMed), LILACS, SciELO, and BIREME, encompassing articles from January 2010 to May 2020, with no restrictions of language and place of publication.

RESULTS:

A total of 148 articles with the potential to be included were retrieved. Of these, two answered the research question, which consisted of seeking evidence of the ototoxic effects of hydroxychloroquine. These studies scored 11 in their quality assessment with the modified protocol by Pithon et al.13.

CONCLUSIONS:

The studies reported possible ototoxicity of HCQ. Audiovestibular changes, such as hearing loss, peripheral vestibular syndrome, and tinnitus were evidenced in patients submitted to HCQ. The improvement in the audiological examinations and the regression in the vestibular syndrome after stopping the treatment with HCQ are strong arguments in favor of the ototoxicity caused by this medication. However, there are still divergences about the relationship between ototoxic effects and the use of HCQ.

OBJECTIVES:

This review aimed to explore and summarize information from available cases of pediatric acute hydroxychloroquine overdose with confirmed hydroxychloroquine exposure to give the clinicians a helpful perspective for its better recognition and management.

METHODS:

Electronic searches were conducted in PubMed/MEDLINE, Web of Science, Scopus, EBSCO and Serbian Citation Index. The abstracts from 2 toxicology conferences were manually checked for additional relevant publications, as well as reference lists of the retrieved publications. Descriptive statistics, narrative summation, and tabulation of the extracted data were made.

RESULTS:

Nine publications and a total of 9 patients were included in the review. Reported age of the patients varied from 2.5 to 16 years (median, 16 years). There were more female patients (77.8%). Estimated total ingested hydroxychloroquine dose was reported in 7 cases (77.8%), and it ranged from 4.0 to 20.0 g (median: 12.0 g). Four patients (44.4%) ingested hydroxychloroquine with a coingestant. Altered mental status (100.0%), cardiotoxicity (88.9%), hypotension (77.8%), and hypokalemia (55.6%) were the most commonly reported clinical manifestations. The majority of the patients were hospitalized (88.9%). More than half of the patients (55.6%) were reported to be treated in the intensive care unit. Most frequently reported therapeutic measures were the following: administration of intravenous fluids/infusions (77.8%), vasopressors (77.8%), bicarbonate therapy-sodium bicarbonate (66.7%), potassium replacement (55.6%), and intubation/ventilation (55.6%). Three patients (33.3%) died.

CONCLUSIONS:

Management of acute hydroxychloroquine overdose in children should be symptomatic and tailored to observed clinical manifestations. There is a need for additional investigations to better understand the impact and effectiveness of various treatment options.

INTERVENTION:

Intervention 1: Intervention group: hydroxychloroquine, 400 mg BD on the first day and 200 mg hydroxychloroquine BD daily on the second to seventh day and concurrent, Azithromycin at a dose of 500 mg on the first day and then 250 mg daily until the seventh day . The two groups will receive standard treatment. Intervention 2: Control group: hydroxychloroquine, 400 mg BD on the first day and 200 mg hydroxychloroquine BD daily on the second to seventh day. Increasing the duration of treatment to 10 days, according to the doctor's order. The control group will receive placebo instead of Azithromycin.

CONDITION:

COVID‐19 COVID‐19. ; U07.1 ‐ COVID‐19

PRIMARY OUTCOME:

In‐hopital mortality. Timepoint: once. Method of measurement: Medical records. Length of stay in the intensive care unit. Timepoint: Once (when discharged from intensive care unit). Method of measurement: Hospital records.

SECONDARY OUTCOME:

Adverse drug reactions. Timepoint: Daily. Method of measurement: Adverse Drug Reaction forms. Dyspnea. Timepoint: Daily. Method of measurement: Patient medical records. Fever. Timepoint: Daily. Method of measurement: Patient medical records. Laboratory Treatment Response; return of blood cell count and CRP values to normal. Timepoint: Daily. Method of measurement: Laboratory kits. Length of stay in hospital. Timepoint: Once at discharge. Method of measurement: Patient medical records. Oxygen saturation without supplemental oxygen. Measurement will be done after discontinuation of oxygen therapy for 5 minutes. Timepoint: 4 times a day while in the wards. Method of measurement: Observation. Radiological Treatment Response (CT scan) , more than 50% reduction in the affected area. Timepoint: CT scan will be done twice (once at the time of admission and the second time 10 days after discharge). Assessment will be done comparing the second CT with the first one. Method of measurement: Patient CT scan.

INCLUSION CRITERIA:

Diagnosis of COVID‐19 based on either ground glass appearance in chest CT scan or positive RT‐PCR test for COVID‐19 Requiring hospitalization on the basis of level of consciousness,blood pressure, kidney and liver failure Patient's age between 16 and 100 years Signed informed consent form

BACKGROUND:

Hydroxychloroquine (HCQ) has recently been reported to be a promising and safe anti-proteinuric agent for IgA nephropathy (IgAN) patients. In the present systematic review, we aimed to summarize the evidence concerning the benefits and risks of HCQ therapy in IgAN.

METHODS:

Electronic databases were searched for randomized, cohort, or case-control studies with IgAN biopsy-proven patients comparing the effects of HCQ with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or immunosuppression on proteinuria reduction.

RESULTS:

Five studies, one randomized and three observational, involving a total of 504 patients, were eligible for inclusion. Overall, there was a tendency of HCQ treatment to reduce proteinuria. In the studies where the control arm was supportive therapy, HCQ significantly reduced proteinuria at 6 months. However, in the studies that compared HCQ to immunosuppressive therapy, we found no difference in proteinuria reduction. HCQ had no impact on eGFR.

CONCLUSION:

HCQ seems to be an efficient alternative therapy for patients with IgAN who insufficiently respond to conventional therapy. However, ethnically diverse randomized controlled studies with long-term follow-up are needed.

This Phase III trial four treatment strategies non-critically ill hospitalized participants (not requiring intensive care unit (ICU) admission and/or mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin.

This study will evaluate the safety, tolerability and efficacy (objective response rate) of using hydroxychloroquine (HCQ) in combination with nivolumab and ipilimumab or with nivolumab alone in subjects with advanced/metastatic melanoma.

This is an open-label, non-randomized clinical trial study. The number of 40 COVID-19 patients with moderate severity will be admitted in progressive care units (PCUs) and intensive care units (ICUs) enrolled in the study. The sampling will be purposive and based on the same independent variables, including age, gender, past medical histories, and the situation of the patient at the admission day, and ventilator support. The patients will be allocated into two groups with different regimens. Group \"A\" (regimen A)will be defined as Favipiravir 1600 mg a first dose and 600 mg in 3 divided doses daily plus 400 mg in 2 divided doses of Hydroxychloroquine every day. The group \"B\" (regimen B) will be contained 400 mg of Lopinavir/Ritonavirin 2 divided doses plus the first dose (400 mg) of Hydroxychloroquine. Hydroxychloroquine will not be used for adverse drug reactions. The regimen remained at least 7 up to 10 days.

Data will be analyzed using statistical package for social sciences (SPSS) version 18 (SPSS Inc. Chicago, IL, USA) for windows. The variables will be compared using independent and paired T-test for normally distributed variables and Wilcoxon, Chi-square for non-normal distributed variables. The Kaplan Meier test will be used for survival analysis and the one-sample Kolmogorov-Smirnov test for the evaluation of distributions.

The current outbreak of COVID-19 caused by SARS-CoV-2 is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (\>9500) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 replication and anecdotal reports from COVID-19 patients in China and France suggest that chloroquine or hydroxychloroquine is a good candidate for treatment. In the French study a favourable effect was seen when hydroxychloroquine was used together with azithromycin in a small series of COVID-19 patients. However, so far all published evidence is based on non-controlled use of hydroxychloroquine.

We propose to conduct a placebo-controlled trial in COVID-19 patients with mild to moderate disease in Germany to assess virological efficacy, tolerability and safety of hydroxychloroquine in the treatment of COVID-19. The objective of this trial is to identify an effect of hydroxychloroquine on viral clearance in vivo. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post-exposure prophylaxis of COVID-19.

BACKGROUND:

The global spread of COVID-19 and the lack of definite treatment have caused an alarming crisis in the world. We aimed to evaluate the outcome and potential harmful cardiac effects of hydroxychloroquine and azithromycin compared to hydroxychloroquine alone for COVID-19 treatment.

METHODS:

PubMed, Medline, Google Scholar, Cochrane Library, clinicaltrials.gov, and World Health Organization clinical trial registry were searched using appropriate keywords and identified six studies using PRISMA guidelines. The quantitative synthesis was performed using fixed or random effects for the pooling of studies based on heterogeneities.

RESULTS:

The risk of mortality (RR=1.16; CI.: 0.92-1.46) and adverse cardiac events (OR=1.06; CI.: 0.82-1.37) demonstrated a small increment though of no significance. There were no increased odds of mechanical ventilation (OR=0.84; CI.: 0.33-2.15) and significant QTc prolongation (OR=0.84, CI.: 0.59-1.21). Neither the critical QTc threshold (OR=1.92, CI.: 0.81-4.56) nor absolute ?QTc ?60ms (OR=1.95, CI.:0.55-6.96) increased to the level of statistical significance among hydroxychloroquine and azithromycin arm compared to hydroxychloroquine alone, but the slightly increased odds need to be considered in clinical practice.

CONCLUSIONS:

The combination of hydroxychloroquine and azithromycin leads to small increased odds of mortality and cardiac events compared to hydroxychloroquine alone. The use of hydroxychloroquine and azithromycin led to increased odds of QT prolongation, although not statistically significant.