Quinine vs. Artemether/Lumefantrine in Uncomplicated Malaria During Pregnancy

Condition(s) targeted: Malaria

Intervention: Quinine (Drug); artemether / lumefantrine (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Epicentre

Official(s) and/or principal investigator(s):
Patrice Piola, MD, MPH, Principal Investigator, Affiliation: Epicentre
Philippe J Guerin, MD, MPH, PhD, Study Chair, Affiliation: Epicentre
Elizabeth Ashley, MB BS, Study Chair, Affiliation: Epicentre
Rose McGready, MD, PhD, Study Chair, Affiliation: Shoklo Malaria Research Unit (SMRU)
François Nosten, MD, PhD, Study Chair, Affiliation: SMRU

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.

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)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42 or at delivery.

Secondary outcome:

Pharmacokinetic parameters

Incidence of adverse events

Pregnancy outcome

Infant development during the first year of life

Histopathological findings in the placenta

Detailed 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

Minimum age: N/A. Maximum age: N/A. Gender(s): Female.

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.

Epicentre, Mbarara, Mbarara District, Uganda

Starting date: October 2006
Last updated: May 12, 2010