Intermittent Preventive Treatment for Malaria in Patient With Sickle Cell Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01319448
Recruitment Status : Completed
First Posted : March 21, 2011
Last Update Posted : March 21, 2014
Medical Research Council Unit, The Gambia
Wellcome Trust
University of Ilorin Teaching Hospital
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

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.

Condition or disease Intervention/treatment Phase
Malaria Sickle Cell Crisis Drug: Proguanil Drug: mefloquine plus artesunate Drug: Sulfadoxine-pyrimethamine plus amodiaquine Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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 Start Date : September 2011
Actual Primary Completion Date : April 2013
Actual Study Completion Date : April 2013

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

Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: 12 months ]
  2. Adherence to the recommended regimen [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Efficacy against malaria [ Time Frame: 12 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01319448

Department of Paediatrics and Child Health, University of Ilorin Teaching Hospital
Ilorin, Kwara, Nigeria
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Medical Research Council Unit, The Gambia
Wellcome Trust
University of Ilorin Teaching Hospital
Study Chair: Paul J Milligan, PhD LSHTM
Study Director: Kalifa Bojang, PhD MRC Laboratories
Principal Investigator: Rasaq Olaosebikan, MD University of Ilorin

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: London School of Hygiene and Tropical Medicine Identifier: NCT01319448     History of Changes
Other Study ID Numbers: 5856
First Posted: March 21, 2011    Key Record Dates
Last Update Posted: March 21, 2014
Last Verified: March 2014

Keywords provided by London School of Hygiene and Tropical Medicine:
Sickle cell disease
Intermittent Preventive Treatment (IPT)

Additional relevant MeSH terms:
Anemia, Sickle Cell
Protozoan Infections
Parasitic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Fanasil, pyrimethamine drug combination
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents