22 research outputs found
Vaccins et traitements de la pandémie à Coronavirus SARS-CoV-2 : évidences scientifiques, dangers et essais cliniques: Vaccines and treatments for the Coronavirus SARS-CoV-2 pandemic: scientific evidence, dangers, and clinical trials
Since December 2019, an emerging disease due to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) and called coronavirus (COVID-19), has spread quickly around the world from Wuhan, China; leading to an ever-increasing number of confirmed cases and deaths. Unfortunately, to date no drug or vaccine has yet been approved or recommended universally; current therapies are essentially supportive or compassionate. Several options are being considered or under study, including vaccines, antibiotics (azithromycin), antiviral agents (lopinavir, ritonavir, ribavirin, arbidol), anti-parasitic agents (chloroquin, hydroxychloroquin, ivermectin), immunomodulators and other molecules of the immune system (tocilizumab, interferons) and traditional medicine plants.
Depuis décembre 2019, une maladie émergente à coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV) appelée coronavirus disease 2019 (COVID-19) s’est rapidement propagée dans le monde entier à partir de Wuhan en Chine, entrainant un nombre toujours plus élevé de cas confirmés et des décès. Malheureusement, à ce jour aucun médicament ou vaccin n’a encore été approuvé ou recommandé universellement, les thérapeutiques actuelles sont essentiellement de soutien ou compassionnelles. Plusieurs options sont envisagées ou en étude comprenant les vaccins, les antibiotiques (azithromycine), les agents antiviraux (lopinavir, ritonavir, Ribavirin, Arbidol), antiparasitaires (chloroquine, hydroxychloroquine, ivermectine), les immunomodulateurs et autres molécules du système immunitaire (Tocilizumab, interférons), les plantes de la médecine traditionnelle.
 
Pyronaridine–artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm, open-label, cohort event monitoring study
BACKGROUND
In Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine-artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa.
METHODS AND FINDINGS
This single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine-artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine-artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2Ă— rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2Ă— the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2Ă— ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2Ă—ULN. No protocol-defined hepatic events occurred following pyronaridine-artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated.
CONCLUSIONS
Pyronaridine-artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine-artesunate as an operationally useful addition to the management of acute uncomplicated malaria.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03201770