Intermittent Preventive Treatment With Antimalarials in Kenyan Infants

This study has been completed.
Sponsor:
Collaborators:
Kenya Medical Research Institute
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT00111163
First received: May 17, 2005
Last updated: September 26, 2012
Last verified: September 2012
  Purpose

The purpose of the study is to see whether antimalarial drugs administered at the time of routine infant vaccinations prevents malaria and anemia in the first year of life.


Condition Intervention
Malaria
Anemia
Drug: sulfadoxine-pyrimethamine with artesunate
Drug: amodiaquine with artesunate
Drug: chlorproguanil-dapsone

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Efficacy and Safety of Pediatric Immunization-linked Preventive Intermittent Treatment With Antimalarials in Decreasing Anemia and Malaria Morbidity in Rural Western Kenya

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • Clinical malaria in the first year of life

Secondary Outcome Measures:
  • Moderate and severe anemia in the first year of life
  • Serologic responses to Expanded Program on Immunization (EPI) vaccines (Polio, Diphtheria, Tetanus, Pertussis, Hepatitis B, Hemophilus Influenzae type B, and Measles)
  • Nasal carriage rates of Haemophilus influenza type b
  • All cause hospitalization in the first year of life

Estimated Enrollment: 1516
Study Start Date: March 2004
Study Completion Date: March 2008
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Detailed Description:

Approximately three quarters of preschool children in eastern Africa suffer from anemia, defined as a hemoglobin (Hb) concentration below 11 g/dL. For children < 5 years of age, the overall incidence of severe malarial anemia (Hb < 5 g/dl) is estimated at 15-60 cases per 1,000 children per year. Other studies have confirmed that the burden of malaria-related anemia falls primarily on infants and young children. In 2000, Schellenberg and colleagues, working in an area of Tanzania with a low to moderate level of Plasmodium falciparum transmission and a low level of sulfadoxine-pyrimethamine (SP) resistance, demonstrated that by linking intermittent prophylaxis to routine immunization visits through the national Expanded Program on Immunization (EPI), SP could be administered to children at 2,3, and 9 months of age, resulting in a 59% reduction in rates of clinical malaria and a 50% reduction in the rate of severe anemia (Hb<8 g/dl) compared to those receiving placebo. This randomized, double blind, placebo-controlled trial is being conducted to estimate the efficacy of Intermittent Preventive Treatment for Infants (IPTi) with SP + three doses of artesunate (AS) (SP/AS3) given in combination with iron supplementation from 2-6 months of age at routine EPI visits on the prevention of clinical malaria, moderate anemia, and severe anemia in the first 18 months of life in an area with intense malaria transmission and near universal ownership of insecticide treated nets (ITNs). The primary objective is to compare the efficacy of iron supplementation and IPTi with one of 3 antimalarial regimens (SP/AS3, chlorproguanil-dapsone (Lapdap), or AQ/AS3) given at routine EPI visits with iron supplementation alone (+ placebo) on the prevention of clinical malaria in the first year of life. Specific secondary objectives are: 1) Compare the efficacy of iron supplementation plus IPTi with one of 3 antimalarial regimens (SP/AS3, Lapdap [chlorproguanil-dapsone], or AQ/AS3) given at routine EPI visits with iron supplementation alone (+ placebo) on the prevention of moderate and severe anemia in the first year of life; 2) Assess the impact of IPTi with the aforementioned regimens on serologic responses to EPI vaccines (Polio, Diphtheria, Tetanus, Pertussis, Hepatitis B, Hemophilus Influenzae type B, and Measles; 3) Assess the impact of IPTi with the aforementioned regimens (particularly SP/AS3) on the nasal carriage rates of Haemophilus influenza type b; and 4) Compare the efficacy of iron supplementation and IPTi with one of 3 antimalarial regimens (SP/AS3, Lapdap [chlorproguanil-dapsone], or AQ/AS3) given at routine EPI visits with iron supplementation alone (+ placebo) on the prevention of all-cause hospitalization in the first year of life. This trial will generate important public health information on the efficacy of IPTi in preventing anemia and clinical malaria among infants in an area with intense malaria transmission and ongoing prevention efforts through the use of insecticide treated nets. This trial will contribute towards understanding IPTi's mechanism of action (i.e. through intermittent clearance of parasites vs. a chemoprophylactic effect afforded through the use of an antimalarial with a long half-life). The information gained will be useful to determine the safety of IPTi, and to decide what sort of antimalarials are appropriate for IPTi, and ultimately will help to direct child survival and malaria control policy in African countries. If alternative drug regimes to SP prove effective, that information will be valuable to policymakers as levels of P. falciparum resistance to SP rise with increased usage in east Africa.

  Eligibility

Ages Eligible for Study:   5 Weeks to 16 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Presenting for Pentavalent 1 immunization
  • Age 5 weeks to 16 weeks
  • Parent or guardian currently resident in study catchment area
  • Parent or guardian has given permission for their child to participate

Exclusion Criteria:

  • Known allergy to any of the study drugs
  • Current Cotrimoxazole prophylaxis
  • Concomitant disease requiring hospitalization or transfusion
  • Plans to be away from the study area for more than 6 months during the next year
  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: NCT00111163

Locations
Kenya
Lwak, Abidha, Ongielo and Saradidi clinics
Asembo (Rarieda Division), Nyanza Province, Kenya
Sponsors and Collaborators
Kenya Medical Research Institute
Bill and Melinda Gates Foundation
Investigators
Principal Investigator: Robert D Newman, MD, MPH U.S. Centers for Disease Control and Prevention
Principal Investigator: Laurence Slutsker, MD, MPH U.S. Centers for Disease Control and Prevention
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT00111163     History of Changes
Other Study ID Numbers: CDC-NCID-3606, SSC 701
Study First Received: May 17, 2005
Last Updated: September 26, 2012
Health Authority: United States: Federal Government
Kenya: Kenya Medical Research Institute

Keywords provided by Centers for Disease Control and Prevention:
malaria
anemia
Plasmodium falciparum
infants
prevention
safety
efficacy
antimalarials

Additional relevant MeSH terms:
Anemia
Malaria
Hematologic Diseases
Protozoan Infections
Parasitic Diseases
Amodiaquine
Antimalarials
Dapsone
Pyrimethamine
Sulfadoxine
Artesunate
Chlorproguanil
Sulfadoxine-pyrimethamine
Proguanil
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents, Urinary
Renal Agents
Amebicides
Antimetabolites

ClinicalTrials.gov processed this record on July 23, 2014