Artemisinin-Based Antimalarial Combinations and Clinical Response in Cameroon

University of Yaounde 1

Status and phase: Completed; Phase 3

Conditions: Malaria

Treatments: Drug: Artesunate-Amodiaquine; Drug: Dihydroartemisinine-Piperaquine; Drug: Artemether-lumefantrine combination

Study type: Interventional

Funder types: Other

Identifiers

NCT01845701

A60041

Details and patient eligibility

About

To assess the efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 42 days follow up period in 720 children with acute uncomplicated P. falciparum malaria, in two different endemic ecological areas - Savanna and equatorial forest regions of Cameroon.

We have set as specific objectives:

• To assess the efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 14 and 28 days follow up period in children with acute uncomplicated P. falciparum malaria in two different endemic areas.
• To evaluate the safety of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 42 days follow up period in children with acute uncomplicated P. falciparum malaria.
• To determine parasite clearance time (PCT) and fever clearance time (FCT) following the administration of the three trial regimens.
• To investigate the treatment response based on WHO criteria (WHO, 2003) in patients in all groups after trial.
• To investigate the Single Nucleotide Polymorphisms (SNPs) and microsatellite markers of genes associated with drug resistance

Full description

Methodology Children of either gender, between 6 months (> 5kg) and 10 years of age, with acute uncomplicated P. falciparum infection, who fulfil all of the inclusion and have none of exclusion criteria will be enrolled in the study. They will be randomised to receive the three trial arms, i.e, Study Arm-A: artesunate-amodiaquine, Study Arm-B: dihydroartemisinin-piperaquine and Study Arm-C: artemether-lumefantrine at the ratio of 2:2:1 and will be hospitalised over a 3-day period to facilitate the supervised administration of the study drugs and full clinical and laboratory assessment and observation of early adverse effects. On discharge, participants will be required to report to the study clinic on days 7, 14, 21,28, 35 and 42 or at any other time when clinical sign(s)/symptom(s) of malaria is suspected. The number of participants is about 720 children

Inclusion Criteria

• Children of either gender, aged between 6 months (> 5kg) and 10 years.
• Suffering from acute uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick film with an asexual parasite density of 1,000 to 100,000 parasites/μl.
• Presenting with fever (axillary temperature ≥ 37.5oC) or having a history of fever in the preceding 24 hours.
• Able to ingest tablets orally (either suspended in water or uncrushed with food).
• Willing to participate in the study with written assent from parent/guardian. Parental authorization will be obtained for children less than 8 years old and documented assent of parents/guardians for children 8-10 years.
• Willing and able to attend the clinic on stipulated regular follow-up visits.

Exclusion Criteria

• Any of the following "danger signs of severe malaria": Not able to drink or breast feed Persistent vomiting (>2 episodes within previous 24 hours) Convulsions (>1 episode within previous 24 hours) Lethargic/unconscious

• Signs/symptoms indicating severe/complicated malaria according to WHO criteria (WHO definition).
• Concomitant illnesses, underlying chronic hepatic or renal disease, abnormal cardiac rhythm, hypoglycaemia, jaundice, respiratory distress,
• Serious gastrointestinal disease, severe malnutrition (W/H < 70%) or severe anaemia (haemoglobin < 5 g/dl).
• Known hypersensitivity to the study drugs.

Enrollment: 720 patients

Sex: All

Ages: 6 to 120 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children of either gender, aged between 6 months (> 5kg) and 10 years.
• Suffering from acute uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick film with an asexual parasite density of 1,000 to 100,000 parasites/μl.
• Presenting with fever (axillary temperature ≥ 37.5oC) or having a history of fever in the preceding 24 hours.
• Able to ingest tablets orally (either suspended in water or uncrushed with food).
• Willing to participate in the study with written assent from parent/guardian. Parental authorization will be obtained for children less than 8 years old and documented assent of parents/guardians for children 8-10 years.
• Willing and able to attend the clinic on stipulated regular follow-up visits.

Exclusion criteria

•Any of the following "danger signs of severe malaria": Not able to drink or breast feed Persistent vomiting (>2 episodes within previous 24 hours) Convulsions (>1 episode within previous 24 hours) Lethargic/unconscious

• Signs/symptoms indicating severe/complicated malaria according to WHO criteria (WHO definition).
• Concomitant illnesses, underlying chronic hepatic or renal disease, abnormal cardiac rhythm, hypoglycaemia, jaundice, respiratory distress,
• Serious gastrointestinal disease, severe malnutrition (W/H < 70%) or severe anaemia (haemoglobin < 5 g/dl).
• Known hypersensitivity to the study drugs.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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720 participants in 3 patient groups

Artesunate-Amodiaquine

Experimental group

Description:

As a fixed-dose combination of artesunate-amodiaquine developed by Sanofi-Aventis (France). It has the advantage of being a 3-day regimen usable by all age groups and potentially low cost. tablets are administered per every day at dose of 25mg/67.5mg for those between 4,5kg and 9kg for 48H

Treatment:

Drug: Artesunate-Amodiaquine

Dihydroartemisinine_Piperaquine

Experimental group

Description:

As a fixed-dose combination of dihydroartemisinin-piperaquine which is produced by Fouley (China). It is a potentially low cost 2-day regimen that has been used in children between 5-10kg as half a tablet of 40mg/320mg every day for 48H

Treatment:

Drug: Dihydroartemisinine-Piperaquine

Artemeter-Lumefantrine

Active Comparator group

Description:

This is the active comparator as a fixed-dose combination of artemether and lumefantrine which is produced by Novartis (Switzerland). The drug will be used as the comparator because it is the only fixed-dose combination with artemether currently available. Administered in children as tablets containing Artemether-Lumefantrine at (20mg/120mg) for body weights of 5-10kg every 12H within 48H.

Treatment:

Drug: Artemether-lumefantrine combination