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.

This Phase III trial will utilize four treatment strategies in non-critically ill hospitalized participants (not requiring mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin. Investigators are primarily interested in the time to recovery. In addition to study medications there will be daily symptom surveys for 14 days, then weekly thereafter for 4 weeks resulting in a total duration of follow up of 42 days. During hospitalization, daily symptom surveys will be completed in conjunction withthe study coordinators. On discharge participants will have the option to complete electronic symptom surveys or complete symptom surveys via telephone with study coordinator. In the event that the participant opts for electronic symptom surveys on discharge participants will in addition receive a follow up call from a study coordination every 7 days during the initial 14 day period. In addition, failure to submit a symptom survey will prompt a study follow up call. Data from SOC will be collected from medical records.

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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.

CONTEXTO CLÍNICO: La enfermedad por el Coronavirus 2019 (COVID­19, por su sigla en inglés Coronavirus Disease 2019) es una enfermedad respiratoria de humanos producida por un nuevo coronavirus identificado con la sigla SARS-CoV-2. El 11 de marzo de 2020 la Organización Mundial de la Salud (OMS) declaro la COVID-19 como una pandemia. Desde ese momento hasta este 01 de abril su circulación se ha reportado en 205 países reportándose más de 800.000 casos y la muerte 40.000 personas. El período de incubación de la infección por 2019­nCoV es de 2 a 14 días. La mayor parte de los contagios se producen persona a persona, siendo altamente transmisible.3 La clínica varía desde casos asintomáticos a cuadros febriles con tos y dificultad respiratoria, neumonía y distrés respiratorio. También puede acompañarse de alteraciones gastrointestinales. TECNOLOGÍA: La cloroquina es una droga que se administra por vía oral para el tratamiento de la malaria y su quimioprofilaxis y es bajo estas indicaciones que se encuentra autorizado su uso según la FDA, EMA y ANMAT. Ha demostrado tener actividad in vitro contra el SARS-CoV-2 y otros coronavirus por lo que se ha reportado su uso fuera de prospecto para esta indicación. La hidroxicloroquina (una variante de la cloroquina a la que se le agrega un grupo hidroxilo) se encuentra autorizada en el contexto del tratamiento de enfermedades inflamatorias como la artritis reumatoide, lupus eritematoso sistémico y porfiria cutánea tardía. La actividad in vitro frente al SARS-CoV-2 de la hidroxicloroquina es algo mayor que la que posee la cloroquina y también se ha descripto su uso para el tratamiento de la infeccion por COVID-19 como monodroga y asociado al uso del antibiótico azitromicina. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de cloroquina y/o hidroxicloroquina sola o en combinación en el tratamiento de la infección por COVID-19. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas y guías de práctica clínica (GPC) y recomendaciones de diferentes sistemas de salud. RESULTADOS: Se incluyeron tres ECAs, cinco estudios observacionales, tres ETS y once GPC, acerca del uso de clorloquina, hidroxicloroquina y/o hidroxicloroquina más azitromicina en el tratamiento de la infección por COVID-19. CONCLUSIONES: Evidencia de muy baja calidad proveniente de estudios con un alto nivel de imprecisión en sus resultados, no permitiría establecer la eficacia del uso de cloroquina, hidroxicloroquina o la combinación de hidroxicloroquina y azitromicina en la reducción de la mortalidad en pacientes con infección por COVID-19. Evidencia de baja calidad, sugeriría que la adición de hidroxicloroquina a los cuidados estándares en pacientes con infección moderada por COVID-19, se asociaría a beneficios modestos en cuanto a una mejor resolución de la infección pulmonar y menor número de días con fiebre y/o tos. Sin embargo, debe considerarse un riesgo de aparición de arritmias potencialmente mortales entre un 11% a 13% de pacientes con infección por COVID-19 que han recibido tratamiento con cloroquina (asociada a antibioticoterapia), o hidroxicloroquina asociada a azitromicina. La evidencia disponible sugiere que el riesgo de aparición de este evento adverso, en el caso de la cloroquina, se asociaría al uso de dosis más elevadas del fármaco. El Ministerio de Salud de la Argentina ha emitido recomendaciones condicionales a la aparición de nueva evidencia, en un contexto de ausencia o escasez de terapias alternativas para esta patología, a favor del uso de hidroxicloroquina sola o en combinación en casos de infección por COVID-19. Recomendaciones provenientes de entidades como la Organización Mundial de la Salud, el Centro de Control de Infecciones de los Estados Unidos (CDC), o el gobierno de Canadá, basándose en la baja calidad de la evidencia actualmente disponible, no recomiendan el uso de ninguna de estas drogas en pacientes con infecciones por COVID-19. Algunas organizaciones aclaran que su uso solo debería realizarse en el contexto de un ensayo clínico, mientras que consensos de expertos en China e Italia (Lombardía) recomiendan el uso de hidroxicloroquina sola o combinada con azitromicina. Al momento de realizar este documento es muy alta la incertidumbre asociada a la eficacia de la cloroquina y/o hidroxicloroquina, sola o en combinación con azitromicina, en el tratamiento y/o profilaxis de la infección por COVID-19, debido a que la evidencia disponible es de baja calidad metodológica y sus resultados no son consistentes entre los estudios. Esta incertidumbre, junto con aspectos acerca de su seguridad, no permiten emitir una recomendación a favor de su empleo. Sin embargo, es importante tener en cuenta que dado el presente contexto dinámico - se encuentran en curso más de 60 estudios experimentales- es probable que la incertidumbre actualmente existente se reduzca en el corto a mediano plazo.

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 study is a randomized placebo controlled multicentric Phase III trial. The duration of the trial for each subject is expected to be 6 months. The duration for each individual subject includes 7 days study treatment and 6 months follow-up time. Recruitment of subjects will start in April 2020. Adult male and female patients with positive COVID-19 diagnosis and fulfilling the below outlined inclusion criteria will be enrolled into the study. Trial population will consist of both genders. Name of IMP: Hydroxychloroquine sulfate (HCQ); Quensyl. All consenting adult patients having confirmed COVID-19 will be recruited and randomly and blindly allocated in a 1:1 ratio to either IMP or placebo. Each patient will be given a first dose of 800 mg IMP or the equivalent number of placebo capsules (4 capsules) at the day of inclusion (Day 1). From the 2nd day on, each patient will get 600 mg or the equivalent number if placebo capsules (3 capsules) once a day until day 7 (6 more does of 600 mg). The patient will be given the daily dose of IMP at once for a total of 7 days. Patients will be monitored on a daily basis until the endpoint (2 measurements of viral load below 100 copies at least 24 hours apart) is reached. During admission visits will be performed by the attending physician or study-nurse, after discharge visits will be performed by qualified and trained study-personnel. Daily procedures will include a pharyngeal swab for qPCR diagnostics (until primary endpoint is reached) and symptom assessment by questionnaire and clinical examination. Blood draw for assessment of full blood count, routine clinical chemistry and assessment of markers of inflammation, and immune response will be performed on days 1, 2, 4, 7, 14, 30 and last follow up. ECG and measurement of cardiac enzymes will be performed on a weekly basis or if clinically indicated to identify new onset arrhythmias. The efficacy will be assessed by the daily throat swaps and directly followed measurement of SARS-CoV-2-specific RNA copy number until the result of this test will be below the level of detection during at least 2 consecutive visits (24h apart). Safety will be assessed daily by the study physician until the endpoint is reached and at all subsequent scheduled visits and contacts as well as at any unscheduled visit.

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.