Quinine vs. Artemether/Lumefantrine in Uncomplicated Malaria During Pregnancy

Malaria Clinical Trial

Official title: A Randomised, Open-label Non-inferiority Trial of Artemether-lumefantrine Versus Quinine for the Treatment of Uncomplicated Falciparum Malaria During Pregnancy, Mbarara, Uganda (2006-2007)

Status Completed

Clinical Trial 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.

Clinical Trial Description

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 ;

Related Conditions & MeSH terms

• Malaria

• NCT number: NCT00495508
• Study type: Interventional
• Source: Epicentre
• Status: Completed
• Phase: Phase 4
• Start date: October 2006
• Completion date: June 2009