Quinine vs. Artemether/Lumefantrine in Uncomplicated Malaria During Pregnancy
- Registration Number
- NCT00495508
- Lead Sponsor
- Epicentre
- Brief 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.
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 300
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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Quinine Quinine - Arthemeter lumefantrine artemether / lumefantrine -
- Primary Outcome Measures
Name Time Method PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42 or at delivery. 3 years
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (1)
Epicentre
🇺🇬Mbarara, Mbarara District, Uganda