Clinical trial NCT01319448: Intermittent Preventive Treatment for Malaria in Patient With Sickle Cell Disease
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Malaria
Sickle Cell Crisis
Keywords: Sickle cell disease
Malaria
Intermittent Preventive Treatment (IPT)
prophylaxis
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Medical Research Council Unit, The Gambia
name: Wellcome Trust
name: University of Ilorin Teaching Hospital
First posted: 2011-03-21
Enrollment: 270
Sex: ALL
Minimum age (years): 6
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events
timeFrame: 12 months
measure: Adherence to the recommended regimen
timeFrame: 12 months
Secondary outcomes:
measure: Efficacy against malaria
timeFrame: 12 months
Other outcomes:
Locations:
city: Ilorin
country: Nigeria
facility: Department of Paediatrics and Child Health, University of Ilorin Teaching Hospital
state: Kwara
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Paul J Milligan, PhD
role: STUDY_CHAIR
affiliation: MRC Laboratories
name: Kalifa Bojang, PhD
role: STUDY_DIRECTOR
affiliation: University of Ilorin
name: Rasaq Olaosebikan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Olaosebikan R, Ernest K, Bojang K, Mokuolu O, Rehman AM, Affara M, Nwakanma D, Kiechel JR, Ogunkunle T, Olagunju T, Murtala R, Omefe P, Lambe T, Bello S, Ibrahim O, Olorunsola B, Ojuawo A, Greenwood B, Milligan P. A Randomized Trial to Compare the Safety, Tolerability, and Effectiveness of 3 Antimalarial Regimens for the Prevention of Malaria in Nigerian Patients With Sickle Cell Disease. J Infect Dis. 2015 Aug 15;212(4):617-25. doi: 10.1093/infdis/jiv093. Epub 2015 Feb 20.