Clinical trial NCT01845701: Artemisinin-Based Antimalarial Combinations and Clinical Response in Cameroon
Official title: Phase III Study to Study the Clinical Response to ACT Fixed Dose Combination in 42 Days in Uncomplicated Malaria in Cameroon
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Keywords: malaria, cure rate, efficacy, safety
Lead sponsor: University of Yaounde 1
Sponsor class: OTHER
Collaborators: name: World Health Organization
name: Gates Malaria Partnership
First posted: 2013-05-03
Enrollment: 720
Sex: ALL
Minimum age (years): 6
Maximum age (years): 120
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Efficacy
timeFrame: 42 days
Secondary outcomes:
measure: Safety by measure of changes in Physiologic, Blood, Liver and Kidney functions to define AE & SAEs
timeFrame: 42 days
Other outcomes:
Locations:
city: Garoua
country: Cameroon
facility: L'Hopital de District Ngong, Garoua,
state: North
city: Mutengene
country: Cameroon
facility: Baptist Hospital
state: South West
Study officials:
affiliation: University of Yaounde 1
name: Wilfred F Mbacham, ScD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nji AM, Ali IM, Moyeh MN, Ngongang EO, Ekollo AM, Chedjou JP, Ndikum VN, Evehe MS, Froeschl G, Heumann C, Mansmann U, Ogundahunsi O, Mbacham WF. Randomized non-inferiority and safety trial of dihydroartemisin-piperaquine and artesunate-amodiaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroonian children. Malar J. 2015 Jan 28;14:27. doi: 10.1186/s12936-014-0521-2.