Malaria, Sickle Cell Crisis
Conditions
Keywords
Sickle cell disease, Malaria, Intermittent Preventive Treatment (IPT), prophylaxis
Brief summary
Malaria prophylaxis is recommended for sickle cell disease patients. In Nigeria, daily proguanil or weekly pyrimethamine are the most commonly prescribed regimens, but the current policy is not effective due to poor compliance and drug resistance. Intermittent treatment with a long acting drug regimen administered under supervision at clinic visits may be more effective. The aim of this trial is to compare the tolerability and acceptability of supervised bimonthly treatment with either sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) or mefloquine plus artesunate (MQ+AS), with the daily proguanil. Two hundred and seventy patients with sickle cell disease attending the paediatric sickle cell disease clinic in Ilorin hospital who meet the eligibility criteria and have parental consent, will be randomized to one of three prophylactic regimens: daily proguanil, bimonthly sulfadoxine-pyrimethamine plus amodiaquine, or bimonthly mefloquine plus artesunate. Patients will be asked to return to clinic every two months and whenever they are sick. At enrollment, the study paediatrician will conduct a physical examination of the child, and collect a venous blood sample for a complete blood cell count and biochemical screen, determination of G6PD genotype, preparation of blood smears for malaria microscopy and a blood spot for determination of molecular markers of resistance. Four days after each clinic visit, patients will be interviewed (by phone and, for a subset, at home or in the clinic) to ask about compliance and adverse events. Participants will be followed for one year. The parents or carer will be encouraged to bring their child to the Outpatient Department clinic if the child becomes unwell. The primary outcome of the trial is tolerability, secondary outcomes are adherence to the regimen, and incidence of malaria and the number of hospitalizations over 12 months. If the bimonthly regimens are well tolerated and the preliminary data from this study are promising, a larger multicentre trial will be required to determine efficacy.
Interventions
DRUGProguanil
Proguanil tablets, 1.5mg/kg/day
This treatment is given once a day for 3 days. Patients weighing 5-8 kg receive one paediatric tablet per day, those weighing 9-17 kg two paediatric tablets, those weighing 18-29 kg one adult tablet and those weighing 30 kg and two adult tablets.
amodiaquine plus sulfadoxine-pyrimethamine supervised at each bimonthly clinic visit (amodiaquine 10mg/kg per day for three days and sulfadoxine-pyrimethamine (25/1.25 mg/kg) on the first day).
Sponsors
Medical Research Council Unit, The Gambia
Wellcome Trust
University of Ilorin Teaching Hospital
London School of Hygiene and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 6months or older and \>=5kg * Sickle cell clinic attendant * Both males and females * Agree to abide by the study protocol * Give informed consent and assent * Not acutely sick at the time of recruitment * Not having additional chronic disease * Hb genotype of SS and SC confirmed by electrophoresis
Exclusion criteria
* known allergy to any of the antimalarial drugs use in the trial, * severe illnesses requiring urgent admission, * treatment with sulfadoxine-pyrimethamine or mefloquine in the previous 2wks * patients on cotrimoxazole prophylaxis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events | 12 months |
| Adherence to the recommended regimen | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy against malaria | 12 months |
Countries
Nigeria
Outcome results
None listed