quinine vs. artemether/lumefantrine in uncomplicated malaria during pregnancy

Conditions: Malaria

Summary: 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

Eligibility criteria:
inclusion criteria: cohort study: * weeks of pregnancy between 13 and 22 weeks * resident in mbarara municipality (radius of 15km from mnrh) * cohort study signed informed consent form 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.

Keywords: quinine artemether lumefantrine malaria uganda artemisinin- based combination therapy pregnancy malaria in pregnancy