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

Sponsor

Bandim Health Project (Other)

Overall Status

Completed

CT.gov ID

NCT04897919

Collaborator

(none)

474

Enrollment

Location

Arms

Actual Duration (Months)

11.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Malaria Effectiveness	Drug: Dihydroartemisinin-piperaquine 160 mg/20 mg Oral Tablet Drug: Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet	Phase 4

Detailed Description

To objective of the study:

To measure the efficacy and safety of AL and DP in children for treating uncomplicated

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

474 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2015

Actual Primary Completion Date :

Oct 1, 2017

Actual Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dihydroartemisinin-piperaquine 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 Dihydroartemisinin-piperaquine is given as recommended by manufacturer and compared to the Artemether-lumefantrine group. Other Names: Eurartesim
Active Comparator: artemether-lumefantrine 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 Artemether-Lumefantrine is given as recommended by manufacturer Other Names: Coartem

Arm

Intervention/Treatment

Experimental: dihydroartemisinin-piperaquine

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

Dihydroartemisinin-piperaquine is given as recommended by manufacturer and compared to the Artemether-lumefantrine group.

Other Names:

Eurartesim

Active Comparator: artemether-lumefantrine

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

Artemether-Lumefantrine is given as recommended by manufacturer

Other Names:

Coartem

Outcome Measures

Primary Outcome Measures

Adequate clinical and parasitological response rate at day 42 [Day 42]
Cumulative percentages of children having successful treatment on day 42.

Secondary Outcome Measures

re-infection vs recrudescence [Day 42]
Cumulative re-infection and recrudescence rates
Haemoglobin level [Day 42]
Haemoglobin measured on day 42

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.