Clinical trial NCT00529620: Three Alternative Drug Regimens for Malaria Seasonal Preventive Treatment in Senegal
Official title: Randomized Trial of Effectiveness and Acceptability of Three Alternative Regimens for Malaria Seasonal Intermittent Preventive Treatment in Senegal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Keywords: Malaria
IPT
preventive treatment
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Cheikh Anta Diop University, Senegal
First posted: 2007-09-14
Enrollment: 1833
Sex: ALL
Minimum age (years): 2
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this trial is to compare the acceptability, efficacy and safety of three alternative drug regimens for use for seasonal Intermittent Preventive Treatment to prevent malaria in children. Children aged 2 months to 5 years will be randomized to receive IPT with one of three regimens during the transmission season: sulfadoxine-pyrimethamine (SP) plus amodiaquine, show to be highly effective for IPT in a recent trial; SP plus piperaquine, used for malaria prophylaxis in China for many years; or Duocotexcin (a combination of piperaquine with an artemisinin).

Detailed description: In areas of seasonal malaria transmission the burden of severe disease and mortality due to malaria is mainly among children under 5 years of age. Intermittent preventive treatment (IPT) with antimalarial drugs given to all children once a month during the transmission season is a promising new strategy for malaria prevention. Seasonal IPT with sulfadoxine-pyrimethamine (SP) and one dose of artesunate resulted in a 90% reduction in incidence of clinical malaria in a recent trial in Senegal (Cisse et al., Lancet 2006). An important consideration is the possible impact of seasonal IPT on the emergence and spread of drug resistant parasite genotypes, the choice of drug regimen is therefore critical. A second trial in Senegal showed that a combination of two non-artemisinin drugs with relatively long half lives (SP and amodiaquine (AQ) over three days) was more effective than SP with artesunate and more effective than AQ with artesunate, in preventing malaria; and very few children developed parasitaemia, so that the potential for drug resistant genotypes to emerge and spread was low. Although SP+AQ was more efficacious than the artemisinin-containing regimens tested, it was associated with a higher frequency of adverse events, especially vomiting, and AQ has a bitter unpleasant taste, and therefore we have concerns about the acceptability of AQ for widespread use for IPT. It is important to select a drug regimen that is not only effective but safe and acceptable to the community. Each treatment is a 3-dose regimen over 3 days, the first dose will be supervised and the other 2 doses given by the mother or carer. One month after each treatment round, children will be visited at home to check for malaria symptoms, children with fever or a history of fever in the last 48 hours will be asked to give a finger prick blood sample for malaria diagnosis. One month after the last treatment all children will be asked to give a finger prick blood sample for parasitology and haemoglobin, axillary temperature will be measured. The child's carer will be interviewed about compliance and adverse events. The endpoints will be the cumulative incidence of malaria, the proportion of children experiencing moderate and severe adverse events, compliance with and acceptability of the regimen, the prevalence of parasitaemia, and the proportion of children carrying parasite genotypes associated with resistance to sulfadoxine or pyrimethamine at the end of the transmission season. Since acceptability is difficult to assess in the formal setting of a trial, and because the method of delivery may affect compliance and acceptability, drug treatments will be delivered by community workers replicating the conditions under IPT would be delivered routinely in Senegal. Treatments will be administered at home by local community workers, each worker covering a circuit of approximately 60-80 children. The community worker circuit will be the unit of randomization, for simplicity in the field to minimise allocation errors, and to avoid contamination due to sharing of tablets within a household.

Eligibility criteria: Inclusion Criteria:

* age 2 to 59 months in September 2007

Exclusion Criteria:

* history of allergy to study drugs

Primary outcomes:
measure: Incidence of malaria
timeFrame: Four months
Secondary outcomes:
measure: Adverse events reported by the mother: vomiting, headache, fever, nausea, diarrhea
timeFrame: within 4 days of the start treatment
measure: Prevalence of P.falciparum parasitaemia
timeFrame: Measured by microscopy 1 month after the last treatment, in December
measure: Haemoglobin concentration
timeFrame: Measured 1 month after the last treatment, in December
measure: The proportion of children carrying P.falciparum genotypes associated with resistance to sulfadoxine and pyrimethamine
timeFrame: Measured in December
measure: Compliance with the treatment regimen
timeFrame: Recorded 4 days after the start of treatment
Other outcomes:
Locations:
city: Dakar
country: Senegal
facility: Departement de Parasitologie et Mycologie, Universite Cheikh Anta Diop
Study officials:
affiliation: Universite Cheikh Anta Diop
name: Badara Cisse, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine
name: Paul J Milligan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cisse B, Cairns M, Faye E, NDiaye O, Faye B, Cames C, Cheng Y, NDiaye M, Lo AC, Simondon K, Trape JF, Faye O, NDiaye JL, Gaye O, Greenwood B, Milligan P. Randomized trial of piperaquine with sulfadoxine-pyrimethamine or dihydroartemisinin for malaria intermittent preventive treatment in children. PLoS One. 2009 Sep 28;4(9):e7164. doi: 10.1371/journal.pone.0007164.