Intermittent Preventive Treatment for Malaria in Patient With Sickle Cell Disease

NCT01319448 | Completed Phase 1 DMC

• 1 other identifier: 5856
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria; Sickle Cell Crisis

Keywords

Sickle cell disease; Malaria; Intermittent Preventive Treatment (IPT); prophylaxis

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  12 months

• Adherence to the recommended regimen

  12 months

Secondary Outcomes (1)

• Efficacy against malaria

  12 months

Study Arms (3)

Daily proguanil

ACTIVE COMPARATOR

Standard policy of a supply of proguanil tablets to be taken daily

Drug: Proguanil

IPT with MQ+AS bimonthly

EXPERIMENTAL

Intermittent Preventive Treatment (IPT) consisting of a bimonthly course of treatment with mefloquine-artesunate (MQ+AS)

Drug: mefloquine plus artesunate

IPT with SP+AQ bimonthly

EXPERIMENTAL

IPT with bimonthly course of treatment with sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ)

Drug: Sulfadoxine-pyrimethamine plus amodiaquine

Interventions

Proguanil DRUG

Proguanil tablets, 1.5mg/kg/day

Daily proguanil

mefloquine plus artesunate DRUG

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.

IPT with MQ+AS bimonthly

Sulfadoxine-pyrimethamine plus amodiaquine DRUG

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).

IPT with SP+AQ bimonthly

Eligibility Criteria

• Age: 6 Months - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Medical Research Council Unit, The Gambia: collaborator
• Wellcome Trust: collaborator
• University of Ilorin Teaching Hospital: collaborator

Study Sites (1)

Department of Paediatrics and Child Health, University of Ilorin Teaching Hospital

Ilorin, Kwara State, Nigeria

Location

Related Publications (1)

• 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.

  PMID: 25701866 DERIVED

MeSH Terms

Conditions

Malaria; Vaso-Occlusive Crises; Anemia, Sickle Cell

Interventions

Proguanil; Mefloquine; Artesunate; fanasil, pyrimethamine drug combination; Amodiaquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Aminoquinolines

Study Officials

• Paul J Milligan, PhD

  London School of Hygiene and Tropical Medicine

  STUDY CHAIR

• Kalifa Bojang, PhD

  MRC Laboratories

  STUDY DIRECTOR

• Rasaq Olaosebikan, MD

  University of Ilorin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2011
• First Posted: March 21, 2011
• Study Start: September 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: March 21, 2014

Record last verified: 2014-03

Locations

NG (1)