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