Impact of Artemisinin-based Combination Therapy and Quinine on Treatment Failure and Resistance in Uncomplicated Malaria (QuinAct)
This is a bi-centric phase IIIb, randomized, open label, 3-arm clinical trial performed to investigate the impact of retreatment with an Artemisinin-Based Combination (ACT), for example Arthemeter-Lumefantrine (AL) in Uganda (Ug) and artesunate-amodiaquine (ASAQ) in RDCongo, on malaria incidence and its potential selection of resistant strains.
Patients will be followed-up for efficacy and safety during 42 days after treatment with the first line therapy recommended by the national authorities(arthemeter-lumefantrine in Uganda and artesunate-amodiaquine in RDCongo) and retreated the patients either with the same ACT or an other ACT or oral Quinine + clyndamicin.
The investigators hypothesize that (re)treatment with the first line ACT treatment beyond 14 days is as efficacious as any other rescue treatment, without the risk of selecting drug resistant strains.
Drug: Quinine + Clindamycin
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Clinical Trial to Measure the Impact of Retreatment With an Artemisinin-based Combination on Malaria Incidence and Its Potential Selection of Resistant Strains|
- Late Parasitological Failure [ Time Frame: Day4-Day28 ] [ Designated as safety issue: No ]Parasitaemia after day 3 in the absence of fever (axillary temperature <37.5°C)
- PCR unadjusted efficacy [ Time Frame: Day 28 days ] [ Designated as safety issue: No ]Proportion of children without (PCR not adjusted) treatment failure (TF28U): all treatment failures detected during the active follow up, regardless of genotyping.
- Day 42 clinical efficacy [ Time Frame: Day 42 ] [ Designated as safety issue: No ]All clinical treatment failures detected during the 42 days follow up for the first line treatment, with and without PCR adjustment. As no active monitoring of parasitaemia after day 3 is planned this includes ETF and LCF following WHO criteria.
- Change in Fever clearance time (FCT) [ Time Frame: Day 0, Day 1, Day 2 ] [ Designated as safety issue: No ]The time (in days) from the time of randomization to the first two consecutive measurements on 2 different days of axillary temperature below 37.5°C.
- Change in Asexual parasite clearance time [ Time Frame: Day 0, Day 1, Day 2 ] [ Designated as safety issue: No ]
Asexual parasite clearance time is defined as the time (in days) from time of randomization to 2 consecutive negative blood slides (collected at different days). The time to the event will be taken as the time to the first negative slide.
5. Gametocytaemia (prevalence and density) at day 7, 14, 21 and 28 after treatment.
- Hb changes [ Time Frame: Day 0, Days 14 and Day 28 ] [ Designated as safety issue: Yes ]Variation in Hb level between two measurements.
- Early Treatment Failure [ Time Frame: Day0-Day3 ] [ Designated as safety issue: No ]Development of danger signs or severe malaria on Day 0, Day 1 Day 2 or Day 3, in the presence of parasitaemia Parasite density on Day 2 > Day 0 count, irrespective of axillary temperature Presence of parasitaemia on Day 3 with fever (axillary temperature ≥ 37.5°C) Parasitaemia on Day 3 ≥ 25 % of count on Day 0.
- Late Clincial Failure [ Time Frame: Day0-Day28 ] [ Designated as safety issue: No ]Development of danger signs or severe malaria after Day 3 in the presence of parasitaemia Presence of parasitaemia and fever on any day from Day 4 to Day 28
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Tablets 20 mg/120 of Artemether/Lumefantrine will be given to 124 trial patients
Tablets containing 20 mg of Artemether and 120 mg of Lumefantrine. Each dose to be taken with high-fat food or drinks (for example milk).
Weight in kg Number of tablet per dose Age 5 to < 15 kg 1 tablet per dose 15 to < 25 kg 2 tablets per dose 25 to < 35 kg 3 tablets per dose
Other Name: Coartem®
Tablets 25mg/67,5 mg of Artesunate/Amodiaquine will be given to 124 trial patients.
Age (Weight in Kg) Dose Treatment duration 2 to 11 months (= 4,5 to < 9kg):1 tablet (25 mg/675mg) for 3 days
1 to 5 years (= 9 kg to < 18 kg)1 tablet(25mg/67,5mg)for 3 days
Other Name: Co-arsucam®
Active Comparator: Quinine + Clindamycin
Quinine tablet 125mg + Clindamycin syrup 75mg/5ml will be given to 60 children.
Drug: Quinine + Clindamycin
this arm consist to 7 days treatment of 60 patients with quinine tablet 125mg + clindamycin syrup as follow;
9 to < 11 kg: ½ tablets 12 to < 19 kg: 1 tablets per dose 20 to < 27 kg: 1½ tablets per dose 28 to < 35 kg: 2 tablets per dose
10 mg/kg twice daily
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|Contact: Jean-Pierre Van geertruyden, MD MPH PhD||++ 32 32652528||Jean-Pierre.VanGeertruyden@ua.ac.be|
|Centre de Santé Lisungi||Recruiting|
|Kinshasa, Mont-Ngafula, Congo, Route Kimwenza n°23|
|Principal Investigator: Hypolite Muhindo Mavoko, MD MPH|
|Kazo Health centre IV||Recruiting|
|Kiruhura, Uganda, P.O Box 5 Rushere|
|Principal Investigator: Carolyn Nabasumba, M.B.Ch.B|
|Principal Investigator:||Hypolite M. Mavoko, MD MPH||Kinshasa University, RDCongo|
|Principal Investigator:||Carolyn Nabasumba, M.B.Ch.B||Kazo health centre IV Uganda|
|Study Director:||Jean-Pierre Van geertruyden, MD MPH PhD||International Health Unit Antwerp university|