Lapdap and Coartemether for Uncomplicated Malaria

Sponsor

London School of Hygiene and Tropical Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT00118794

Collaborator

Medical Research Council (Other), National Malaria Control Programme, The Gambia (Other)

1,200

Enrollment

Location

Duration (Months)

133.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Drug: Chlorproguanil-dapsone (Lapdap) Drug: Lumefantrine-artemether (Coartemether )	Phase 3

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Trial of the Safety and Effectiveness of Lapdap and Coartemether for Uncomplicated Malaria in Operational Settings

Study Start Date :

Sep 1, 2004

Study Completion Date :

Jun 1, 2005

Outcome Measures

Primary Outcome Measures

Clinical failure by day 28 []

Secondary Outcome Measures

Incidence of severe anaemia by day 28 []
Compliance []
Incidence of adverse events []
Parasitological failure by day 28 []
Clinical and parasitological failure rates by day 14 []
Fall in Hb of 2g/dl or more from screening value []

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 10 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Research Council Laboratories	Banjul		Gambia	POBOX273

Sponsors and Collaborators

London School of Hygiene and Tropical Medicine
Medical Research Council
National Malaria Control Programme, The Gambia

Investigators

Principal Investigator: Paul J Milligan, BSc MSc PhD, London School of Hygiene and Tropical Medicine
Principal Investigator: Sam K Dunyo, MD PhD, Medical Research Council