Intermittent Preventive Treatment for Malaria in Patient With Sickle Cell Disease

Study Overview
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Brief Summary
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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.

Official Title
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Safety and Tolerability of Bi-monthly Intermittent Preventive Treatment With Mefloquine-Artesunate or Sulfadoxine-Pyrimethamine Plus Amodiaquine for Prevention of Malaria and Related Complications in Patients With Sickle Cell Anaemia.

Conditions
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Malaria, Sickle Cell Crisis

Intervention / Treatment
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* Drug: Proguanil
* Drug: mefloquine plus artesunate
* Drug: Sulfadoxine-pyrimethamine plus amodiaquine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Daily proguanil<br>Standard policy of a supply of proguanil tablets to be taken daily | Drug: Proguanil<br>* Proguanil tablets, 1.5mg/kg/day<br>|
| Experimental: IPT with MQ+AS bimonthly<br>Intermittent Preventive Treatment (IPT) consisting of a bimonthly course of treatment with mefloquine-artesunate (MQ+AS) | Drug: mefloquine plus artesunate<br>* 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.<br>|
| Experimental: IPT with SP+AQ bimonthly<br>IPT with bimonthly course of treatment with sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) | Drug: Sulfadoxine-pyrimethamine plus amodiaquine<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | 12 months | 
| Adherence to the recommended regimen |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy against malaria |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle cell disease, Malaria, Intermittent Preventive Treatment (IPT), prophylaxis