Quinine vs. Artemether/Lumefantrine in Uncomplicated Malaria During Pregnancy

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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)

Conditions
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Malaria

Intervention / Treatment
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* Drug: Quinine
* Drug: artemether / lumefantrine


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Quinine<br> | Drug: Quinine<br> <br> |
| Active Comparator: Arthemeter lumefantrine<br> | Drug: artemether / lumefantrine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42 or at delivery. |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters |  | 3.5 years | 
| Incidence of adverse events |  | 3 years | 
| Pregnancy outcome |  | 3.5 years | 
| Infant development during the first year of life |  | 3 years | 
| Histopathological findings in the placenta |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Quinine, Artemether, Lumefantrine, malaria, Uganda, Artemisinin- based combination therapy, pregnancy, Malaria In Pregnancy