Intermittent Preventive Treatment for Malaria in Patient With Sickle Cell Disease

This study has been completed.
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT01319448
First received: March 16, 2011
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Malaria
Sickle Cell Crisis
Drug: Proguanil
Drug: mefloquine plus artesunate
Drug: Sulfadoxine-pyrimethamine plus amodiaquine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by London School of Hygiene and Tropical Medicine:

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Adherence to the recommended regimen [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy against malaria [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 270
Study Start Date: September 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

  Eligibility

Ages Eligible for Study:   6 Months to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01319448

Locations
Nigeria
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
Investigators
Study Chair: Paul J Milligan, PhD LSHTM
Study Director: Kalifa Bojang, PhD MRC Laboratories
Principal Investigator: Rasaq Olaosebikan, MD University of Ilorin
  More Information

No publications provided

Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT01319448     History of Changes
Other Study ID Numbers: 5856
Study First Received: March 16, 2011
Last Updated: March 20, 2014
Health Authority: Nigeria: The National Agency for Food and Drug Administration and Control

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

Additional relevant MeSH terms:
Anemia, Sickle Cell
Malaria
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Protozoan Infections
Parasitic Diseases
Amodiaquine
Proguanil
Mefloquine
Pyrimethamine
Sulfadoxine
Artesunate
Sulfadoxine-pyrimethamine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Enzyme Inhibitors
Anti-Infective Agents, Urinary
Renal Agents
Amebicides

ClinicalTrials.gov processed this record on July 20, 2014