Clinical trial NCT00118794: Lapdap and Coartemether for Uncomplicated Malaria
Official title: Randomized Trial of the Safety and Effectiveness of Lapdap and Coartemether for Uncomplicated Malaria in Operational Settings
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Keywords: uncomplicated malaria
G6PD deficiency
haemolytic anaemia
Lapdap
Artemsinin based combination treatment
compliance
pragmatic trials
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Medical Research Council
name: National Malaria Control Programme, The Gambia
First posted: 2005-07-12
Enrollment: 1200
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lapdap (chlorproguanil-dapsone) is an affordable and effective drug, but patients with glucose-6-phosphate dehydrogenase (G6PD) A- deficiency are more susceptible to the haemolytic effects of the dapsone component of Lapdap; therefore there is a need to evaluate the extent to which the risks associated with the use of the drug in settings without G6PD screening might outweigh the benefits to malaria treatment. The investigators will evaluate, in operational settings, the safety and effectiveness of Lapdap and coartemether (lumefantrine-artemether) for treatment of uncomplicated malaria in patients 6 months to 10 years of age.

Detailed description: Patients with uncomplicated malaria will be recruited at three health centres in the Gambia. Children aged 6 months to 10 years presenting with a history of illness, who have a fever or recent history of fever, will be screened; those with uncomplicated malaria, a positive blood smear with a parasite density of 500 to 200,000 parasites/µl, monoinfection with P. falciparum, and a packed cell volume of \>=20%, will be invited to enroll into the study and if consent is given, will be randomized to receive three daily doses of lapdap, or a six-dose course of Coartem. The first dose will be given by the mother under direct observation by the dispensing nurse; subsequent doses will be given at home unsupervised. Children will be followed up actively three times; on day 3, to assess adherence to the treatment regimen, and on days 14 and 28, to assess parasitological and haematological recovery. The mother/caregiver of the child will be encouraged to bring the child to the clinic if the child does not improve or if she is concerned about the child's health. On day 3, the parent/caregiver will be visited at home (after the last dose should have been taken) in order to check for any leftover medication, and to ask about compliance and adverse reactions. A finger prick blood sample will be taken for Hb measurement by haemocue in the field and for a filter paper sample for measurement of drug concentration. The investigators will employ a longitudinal randomized design, whereby subsequent episodes of malaria will be treated according to the original randomization. This will enable better assessment of cumulative effects of repeated treatments on anaemia and on tolerability. Since patients with glucose-6-phosphate dehydrogenase (G6PD) A- deficiency are more susceptible to the haemolytic effects of the dapsone component of Lapdap, the investigators will determine the G6PD genotype and enzymatic activity, in order to evaluate the extent to which the risks associated with the use of the drug in settings without G6PD screening might outweigh the benefits to malaria treatment.

Eligibility criteria: Inclusion Criteria:

* presentation at health centre with febrile illness
* monoinfection with P falciparum
* parasitaemia \>=500/microlitre
* fever or history of fever

Exclusion Criteria:

* signs of severe or complicated malaria (persistent vomiting with or without dehydration, history of convulsion during the present illness, inability to sit or stand, parasitaemia \>200,000/ul)
* severe malnutrition
* clinically evident concomitant disease
* PCV \<20%
* history of allergy to the study medications
* residence outside the study area and hence difficult to follow up

Primary outcomes:
measure: Clinical failure by day 28
Secondary outcomes:
measure: Incidence of severe anaemia by day 28
measure: Compliance
measure: Incidence of adverse events
measure: Parasitological failure by day 28
measure: Clinical and parasitological failure rates by day 14
measure: Fall in Hb of 2g/dl or more from screening value
Other outcomes:
Locations:
city: Banjul
country: Gambia
facility: Medical Research Council Laboratories
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Paul J Milligan, BSc MSc PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical Research Council
name: Sam K Dunyo, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dunyo S, Sirugo G, Sesay S, Bisseye C, Njie F, Adiamoh M, Nwakanma D, Diatta M, Janha R, Sisay Joof F, Temple B, Snell P, Conway D, Walton R, Cheung YB, Milligan P. Randomized trial of safety and effectiveness of chlorproguanil-dapsone and lumefantrine-artemether for uncomplicated malaria in children in the Gambia. PLoS One. 2011;6(6):e17371. doi: 10.1371/journal.pone.0017371. Epub 2011 Jun 7.