Quinine vs. Artemether/Lumefantrine in Uncomplicated Malaria During Pregnancy

Overview

A) for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. The PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion. Newborns will be followed for growth and development indicators.

Study Title: Efficacy and Safety of Quinine vs Artemether/Lumefantrine in uncomplicated malaria during pregnancy, Mbarara, Uganda (2006/2007). Regulatory Status: Investigational - Phase IV Investigational Product and route: * Quinine hydrochloride, oral route. * Coartem® (Novartis Pharma AG, Basel, Switzerland), oral route. Lead Investigator and Study Centre Primary objective - To establish that, in pregnant women with uncomplicated Plasmodium falciparum malaria, the PCR-adjusted efficacy of Artemether/Lumefantrine is not inferior to oral Quinine. Secondary objectives * To define the pharmacokinetics of the combination artemether-lumefantrine (AL) in the treatment of uncomplicated P. falciparum infections in the last two trimesters of pregnancy. * To collect baseline data on maternal, obstetric and infant outcomes. * To estimate the incidence of malaria infection, both microscopic and sub-microscopic (by PCR) during pregnancy. * women attending Mbarara National Referral Hospital (MNRH) ante-natal clinic (ANC). * Women with a positive blood smear during follow-up will be invited to participate in a non-inferiority, open, randomised, non- inferiority trial comparing the efficacy and tolerance of Coartem® (Artemether-Lumefantrine) for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion. * Women with uncomplicated malaria from the efficacy study, will be followed to obtain an efficacy endpoint at 42 days OR at delivery, whichever timepoint is the last. * Newborns will be followed monthly up to the age of 1 year. Inclusion Criteria (Efficacy Study): * Pregnant woman * Malaria infection, detected by microscopy, with P. falciparum (mixed or mono-infection) * Age of gestation: 13 weeks and beyond * Efficacy study signed informed consent form Exclusion Criteria (Efficacy Study): * P. falciparum parasitaemia above 250,000 parasites/μl * Severe anaemia * Signs or symptoms of severe/complicated malaria requiring parenteral treatment (WHO 2000) * Known allergy to artemisinin derivatives, lumefantrine or quinine; * Previous participation in the efficacy study * Inability to attend the efficacy study follow-up schedule. Study drugs and Administration * Group 1 (Active Control): Quinine hydrochloride (10 mg/Kg/8h for 7 days) administered orally. * Group 2 (Test): Coartem®, fixed Artemether-Lumefantrine (20/120 mg) GMP manufactured by Novartis Pharma AG (Basel, Switzerland), 4 tablets twice a day for 3 days with 200 ml of milk tea at each dose . Endpoints \- Primary efficacy endpoint: PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42. * Secondary efficacy endpoints: * PCR-corrected(ACPR)at delivery * Pharmacokinetic parameters * Symptom clearance Time * Proportion of patients who have fever cleared at Day 1, 2 and 3 * Safety endpoints: * Incidence of any adverse events * Pregnancy outcome * Infant development during the first year of life

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Outcomes