Cohort Study in Uganda Comparing Artesunate + Amiodaquine (Coarsucam) Versus Artemether + Lumenfantrine (Coartem) in the Treatment of Repeated Uncomplicated Plasmodium Falciparum Malaria Attacks

Study Overview
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Brief Summary
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Primary objective is to demonstrate the non-inferiority of PCR (Polymerase Chain Reaction) adjusted adequate clinical and parasitological response at Day 28 of Coarsucam versus Coartem, based on the first malaria attack of each patient. Secondary objectives: For the first attack: To compare the 2 groups of treatment in terms of: Day 42 efficacy Parasitological and fever clearance Clinical and Biological tolerability Evolution of gametocyte carriage For attack 2nd and following: To compare the 2 groups of treatment in terms of: Day 28 and Day 42 clinical and parasitological effectiveness Clinical and Biological tolerability Proportion of patients without fever at Day 3 Proportion of patients without parasites at Day 3 Evolution of gametocyte carriage Compliance During the total follow up of the cohort: To compare the 2 groups of treatment in terms of: Treatment incidence density Impact of repeated treatment on clinical and biological tolerability Impact on anaemia Impact on Hackett score.

Official Title
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A Randomised Study to Compare a Fixed Dose Combination of Artesunate Plus Amiodaquine (Coarsucam) Versus a Fixed Dose Combination of Artemether Plus Lumefantrine (Coartem) in the Treatment of Repeated Uncomplicated Plasmodium Falciparum Malaria Attacks Occurring During the 2 Years of Follow-up, in Children in Uganda.

Conditions
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Malaria

Intervention / Treatment
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* Drug: Coarsucam
* Drug: Coartem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Specific inclusion criteria for initial enrollment: Confirmed mono infection with Plasmodium falciparum, with parasite density ≥2000 asexual forms per µl of blood, Inclusion criteria for each attacks: Body weight ≥5 kg Able to be treated by oral route Fever (axillary temperatur ≥37.5 degrees Celsius) at D0 or history of fever within the previous 24 hours Confirmed Plasmodium falciparum infection with positive paratesimia Haemoglobin value ≥5.0 g/dl Exclusion Criteria: Specific exclusion criteria for initial enrollment: Patient participating in another ongoing clinical trial Allergy to one of the investigational medicinal products History of hepatic and (or) haematological impairment during treatment with amodiaquine History of cardiac disease Concomitant febrile illness Exclusion criteria for each attacks: Presence of at least one danger sign of malaria: recent history of convulsions (1-2 within 24h), unconsciousness state, lethargy, unable to drink or breast feed, vomiting everything, unable to stand/sit due to weakness Severe concomitant disease or known disturbances of electrolyte balance such as hypokalaemia or hypomagnesaemia Intake of medication metabolized by cytochrome CYP 2D6 (e.g. metoprolol, flecainide, imipramine, amitriptyline, clomipramine) at the time of inclusion Intake of drugs known to inhibit CYP 2A6 (e.g. methoxsalem, pilocarpine, tranylcypromine) and/or 2C8 cytochromes (e.g. trimethoprim, ritonavir, ketoconazole, montelukast, gemfibrozil) at the time of inclusion Intake of medication known to prolong the QTc interval, such as class IA and III antiarrythmics, neuroleptics, antidepressant agents, certain antibiotics including drugs in the macrolide class, fluoroquinolones, imidazole and triazole, antifungal agents, certain non-sedative anthistamines (terfenadine, astemizole) and cisapride at the time of inclusion Patient having received artesunate + amiodaquine or artemether + lumefantrine at suitable dosage within the previous 2 weeks. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Experimental: 1<br>Coarsucam double-layer artesunate/amiodaquine tablets | Drug: Coarsucam<br>* Oral route, once daily, dose according to bodyweight range Duration of treatment: 3 days<br>|
| Active Comparator: 2<br>Coartem (artemether/lumefantrine) fixed-dose combination tablets | Drug: Coartem<br>* Oral route, twice daily, dose according to bodyweight range Duration of treatment: 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCR corrected and uncorrected clinical and parasitological cure rate |  | At Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fever and parasitological clearance evaluation by measuring the axillary temperature and monitoring paratesimia |  | At the first attack | 
| Proportion of afebrile patients and proportion of patients without parasites |  | At Day 3 (following attacks) | 
| Evolution of baseline symptoms (Clinical efficacy measure) |  | During the study conduct | 
| Number of residual tablets in blisters (compliance) |  | At the end of the study treatment | 
| Treatment incidence density: comparison of the number of malaria attacks between the 2 arms |  | During the 2 years of follow-up | 
| Mean delay between 2 attacks |  | during the 2 years of follow-up | 
| Incidence and intensity of recorded AE |  | from the informed consent signed up to the end of the study | 
| Biological tolerability (Hb, Bilirubin, ALAT, Creatinine, Leucocytes, Neutrophils and Platelets count) |  | During the study conduct | 
| PCR corrected and uncorrected clinical and parasitological cure rate |  | At Day 42 |