Intermittent Preventive Treatment for Malaria in Patient With Sickle Cell Disease

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.

Conditions

• Malaria
• Sickle Cell Crisis

Interventions

DRUG

Proguanil

Proguanil tablets, 1.5mg/kg/day

DRUG

mefloquine plus artesunate

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.

DRUG

Sulfadoxine-pyrimethamine plus amodiaquine

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 & Collaborators

• Medical Research Council Unit, The Gambia

  collaborator OTHER

• Wellcome Trust

  collaborator OTHER

• University of Ilorin Teaching Hospital

  collaborator OTHER

• London School of Hygiene and Tropical Medicine

  lead OTHER

Principal Investigators

• Paul J Milligan, PhD · London School of Hygiene and Tropical Medicine

• Kalifa Bojang, PhD · MRC Laboratories

• Rasaq Olaosebikan, MD · University of Ilorin

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Months

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2011-09-30

Primary Completion

2013-04-30

Completion

2013-04-30

Countries

• Nigeria

Study Locations