Effectiveness and Safety of Artemether + Lumefantrine and Dihydroartemisinin + Piperaquine for Treating Malaria

Study Overview
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Brief Summary
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Objective: to measure the effectiveness and safety of (artemether-lumefantrine) AL and (dihydroartemisinin-piperaquine) DP in patients (> 6 months) suffering from uncomplicated P. falciparum malaria. Patients coming to Bandim Health Center will, if accepting, be randomised to study-arm. Medication will be provided and first dose given. Patients will be followed-up on day 7, 14, 28, and 42 with clinical evaluation, malaria film and filter-paper blood-sample for polumerase chain reaction (PCR) on re-appearing parasites. On day 21 and 35 a telephone-interview will be performed. Primary out-come: adequate clinical and parasitological response rate on day 42. Secondary out-comes: safety, re-infection vs recrudescence, and haemoglobin on day 42.

Detailed Description
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To objective of the study: To measure the efficacy and safety of AL and DP in children for treating uncomplicated P. falciparum malaria. To determine the capacity of each drug combination to protect against re-infection. To differentiate recrudescence from re-infections using PCR based methods To determine haemoglobin values on days 0 and 42 To determine genetic polymorphisms in P. falciparum causing reparasitaemia. Study design This will be an open label, randomized, non inferiority trial conducted at the Bandim Health Centre, Guinea-Bissau. Patients with uncomplicated malaria who meet study inclusion criteria will be enrolled, randomised to treatment with either AL or DP. Medication will be provided and first dose given at the health centre. Efficacy and safety evaluation Treatment outcomes will be early treatment failure, late clinical failure, late parasitological failure or adequate clinical and parasitological response as defined by the WHO. All will be asked routinely about previous symptoms and about symptoms that have emerged since the previous follow up visit. All adverse events will be recorded in the case record forms. 100µL of blood will be collected on Whatman 3MM filter-paper using a capillary tube on day 0, 7, 14, 28,and 42 and whenever re-parasitaemia is detected. Filter-papers will be dried and then placed inside separate sealed plastic bags. In order to differentiate recrudescence from a re-infection genotyping using sequential analysis of pf-glurp, pfmsp1 and pfmsp2 will be done. Drug concentrations will be assessed on the week prior to re-parasitaemia. Haemoglobin concentration will be determined on day 0, 3 and 42 using a haemocueTM.

Official Title
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Effectiveness and Safety of Artemether + Lumefantrine and Dihydroartemisinin + Piperaquine for the Treatment of Uncomplicated Malaria in Guinea-Bissau

Conditions
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Malaria, Effectiveness

Intervention / Treatment
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* Drug: Dihydroartemisinin-piperaquine 160 mg/20 mg Oral Tablet
* Drug: Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mono-infection with P. falciparum detected by microscopy. Parasitemia of 1.000-200.000/µl asexual forms. Axillary temperature ≥37.5 ˚C or a history of fever within 24 hours. Ability to swallow oral medication. Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule. Informed consent Exclusion Criteria: Signs or symptoms of severe malaria Presence of general danger signs in children under 5 Presence of severe malnutrition. Any evidence of chronic disease or acute infection other than malaria. Regular medication which may interfere with antimalarial pharmacokinetics. History of hypersensitivity reactions or contraindications to AL, DP or quinine. Domicile outside the study area.

Ages Eligible for Study
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Minimum Age: 6 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: dihydroartemisinin-piperaquine<br>First dose will be given supervised. The rest will be provided and the parents should take it at home. Dihydroartemisinin-piperaquine dosing as recommended by manufacturer | Drug: Dihydroartemisinin-piperaquine 160 mg/20 mg Oral Tablet<br>* Dihydroartemisinin-piperaquine is given as recommended by manufacturer and compared to the Artemether-lumefantrine group.<br>* Other names: Eurartesim;|
| Active Comparator: artemether-lumefantrine<br>First dose will be given supervised. The rest will be provided and the patients should take it at home. Artemether-lumefantrine dosing as recommended by manufacturer | Drug: Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet<br>* Artemether-Lumefantrine is given as recommended by manufacturer<br>* Other names: Coartem;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adequate clinical and parasitological response rate at day 42 | Cumulative percentages of children having successful treatment on day 42. | Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| re-infection vs recrudescence | Cumulative re-infection and recrudescence rates | Day 42 | 
| Haemoglobin level | Haemoglobin measured on day 42 | Day 42 |