Three Alternative Drug Regimens for Malaria Seasonal Preventive Treatment in Senegal
Information source: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria
Intervention: sulfalene-pyrimethamine plus amodiaquine (Drug); dihydroartemisinin plus piperaquine (Drug); sulfadoxine pyrimethamine plus piperaquine (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: London School of Hygiene and Tropical Medicine Official(s) and/or principal investigator(s): Badara Cisse, PhD, Principal Investigator, Affiliation: Universite Cheikh Anta Diop Paul J Milligan, PhD, Principal Investigator, Affiliation: London School of Hygiene and Tropical Medicine
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).
Clinical Details
Official title: Randomized Trial of Effectiveness and Acceptability of Three Alternative Regimens for Malaria Seasonal Intermittent Preventive Treatment in Senegal
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Incidence of malaria
Secondary outcome: Adverse events reported by the mother: vomiting, headache, fever, nausea, diarrheaPrevalence of P.falciparum parasitaemia Haemoglobin concentration The proportion of children carrying P.falciparum genotypes associated with resistance to sulfadoxine and pyrimethamine Compliance with the treatment regimen
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
Minimum age: 2 Months.
Maximum age: 59 Months.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- age 2 to 59 months in September 2007
Exclusion Criteria:
- history of allergy to study drugs
Locations and Contacts
Departement de Parasitologie et Mycologie, Universite Cheikh Anta Diop, Dakar, Senegal
Additional Information
Starting date: September 2007
Last updated: May 26, 2010
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