Intermittent Preventive Treatment for Malaria in Patient With Sickle Cell Disease

Malaria Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01319448
• Other study ID #: 5856
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 16, 2011
• Last updated: March 20, 2014
• Start date: September 2011
• Est. completion date: April 2013

Study information

• Verified date: March 2014
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Nigeria: The National Agency for Food and Drug Administration and Control
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Months to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Malaria
• Sickle Cell Crisis

Intervention

Drug:
• Proguanil
Proguanil tablets, 1.5mg/kg/day
• 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.
• 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).

Locations

Country	Name	City	State
Nigeria	Department of Paediatrics and Child Health, University of Ilorin Teaching Hospital	Ilorin	Kwara

Sponsors (4)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Medical Research Council Unit, The Gambia, University of Ilorin Teaching Hospital, Wellcome Trust

Country where clinical trial is conducted

Nigeria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events		12 months	Yes
Primary	Adherence to the recommended regimen		12 months	No
Secondary	Efficacy against malaria		12 months	No