Pharmacokinetics of Sulfadoxine-pyrimethamine Plus Amodiaquine for Intermittent Preventive Treatment in Children (IPTc)
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: sulfadoxine-pyrimethamine plus amodiaquine (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: London School of Hygiene and Tropical Medicine Official(s) and/or principal investigator(s): Badara Cisse, PhD, Study Chair, Affiliation: Universite Chiekh Anta Diop Paul Milligan, PhD, Study Director, Affiliation: London School of Hygiene and Tropical Medicine
Summary
The aim of the study is to determine the pharmacokinetic profile of
sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) when used for seasonal Intermittent
Preventive Treatment (IPT) to prevent malaria in children aged 3 to 59 months in Lamarame,
NDoffane District, Senegal. Several studies have shown that seasonal IPT in children can
provide a high degree of protection against clinical malaria. SP+AQ is the most effective
regimen. However little is known about the pharmacokinetics of amodiaquine and
sulfadoxine-pyrimethamine in children. The purpose of this study is to determine the
pharmacokinetics profile of SP+AQ when used for IPT in Senegalese children. 150 children
aged 3 to 59 months will be enrolled in November. They will receive a therapeutic dose of
sulfadoxine-pyrimethamine and amodiaquine, and will be followed up for 30 days. Four finger
prick blood samples will be taken from each child for PK analysis.
Clinical Details
Official title: Pharmacokinetics of Sulfadoxine-pyrimethamine Plus Amodiaquine When Used for Malaria Intermittent Preventive Treatment in Children
Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: Concentration of sulfadoxine, pyrimethamine, and desethylamodiaquine
Secondary outcome: Tolerability
Detailed description:
SP+AQ is the most effective regimen for IPT in children, but there is little information
about the pharmacokinetics of these drugs in children. Although this combination has been
used for many years for treatment of clinical malaria there have been no studies of the
pharmacokinetics of this combination. A recent study described the pharmacokinetics of
amodiaquine when used in combination with artesunate to treat children with clinical malaria
(Stepniewska et al, 2009), and another recent study described the pharmacokinetics of SP in
children with malaria (Barnes et al, 2006), and a further study of SP in children with
uncomplicated malaria demonstrated a low plasma level of the drug in children who failed the
treatment (Obua et al. 2008), but there are no studies of these drugs given together or in
healthy children. This information is important in order to check the bioavailability of the
two drugs when used for IPT and to check the adequacy of the currently recommended dosage.
The study will be conducted in a rural district of Senegal, after holding community meetings
to explain the study. 150 children aged 1-5 years, boys and girls who do not have history of
allergy to study drugs and whose parents agreed for them to participate will be enrolled at
the study clinic. The sample size determination is based on experience from other PK
studies. During the study organization phase, meetings will be held at the health
facilities, members of the community, community leaders, and health staff will be invited to
attend, the investigators will explain, in local language, the aims of the study, the
recruitment and follow up procedures, the total sample size needed, and the duration of
follow up. The detailed schedule for blood sampling will be explained. Subsequently the
investigators will visit families at home to explain the study and invite people to attend
at the clinic. Mothers or carers will be asked to bring the child to the clinic where, after
signing to indicate consent, the child will be weighed and have a clinical examination, a
finger prick blood sample will be taken by drawing blood into a vacutainer, from which 70µL
of blood will be pipetted onto filter paper. SP and the first dose of AQ will be
administered according to the child's weight, the child will be kept under observation for
30 minutes before being allowed to return home. The remaining doses of amodiaquine (days 1
and 2) will be given to a field worker who will visit the child at home to supervise drug
administration. The exact time of the administration will be recorded. Any child who vomits
a dose will be given a repeat dose. The child will be asked to provide a finger prick blood
sample on three further occasions between day 1 and day 28, determined according to a
schedule chosen to allow good estimation of PK parameters. Trained field staff will visit
each child on day 4, to ask about any adverse reactions to the drugs, and on day 14 and 28
to check the child is well. Children with signs of severe malaria, or any other severe
illness, will be referred immediately to the health post. For other children, if the child
has axillary temp >=37. 5oC or a history of fever in the last 48 hours a finger prick blood
sample will be taken for malaria diagnosis by rapid test and blood film to be read later.
Children with a positive test will be treated with Coartem.
Eligibility
Minimum age: 3 Months.
Maximum age: 59 Months.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- age 3 months to 5 years
- no allergy to study drugs
- consent from parent or guardian
Exclusion Criteria:
- chronic illness
Locations and Contacts
Universite Chiekh Anta Diop, Dakar, Senegal
Additional Information
Starting date: April 2011
Last updated: September 16, 2011
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