Antimalarial Drug Resistance in Mali

This study has been completed.
Sponsor:
Collaborator:
Malaria Research and Training Center, Bamako, Mali
Information provided by:
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT00127998
First received: July 7, 2005
Last updated: August 15, 2006
Last verified: August 2006
  Purpose

Resistance of Plasmodium falciparum (malaria) to current antimalarial drugs and the continuing development of resistance to new antimalarial formulations is one of the major obstacles to effective malaria control and case management. Efficient, comprehensive and validated methods for monitoring drug resistance in advance of the development of resistance to the antimalarial drugs that are in use are urgently needed. Molecular markers of genetic polymorphisms that give rise to resistant P. falciparum parasites and methods in population genetics for evaluating the data can be valuable tools for monitoring drug resistance in the field. This study aims to:

  1. Prospectively measure the in vivo response of P. falciparum malaria in Mali to several different antimalarial drugs and drug combinations: chloroquine (CQ), sulfadoxine-pyrimethamine (SP), amodiaquine (AQ), sulfadoxine-pyrimethamine in combination with amodiaquine (SP/AQ), amodiaquine in combination with artesunate (AQ/AS), sulfadoxine-pyrimethamine in combination with artesunate (SP/AS), and artemether-lumefantrine (Co-artem). In one site with preliminary data showing a high rate of P. falciparum resistance to mefloquine (MQ), this drug will also be tested.
  2. Measure the frequencies of molecular markers for antimalarial drug resistance, and examine how those results relate to the efficacy of these drugs in treating clinical malaria
  3. Measure drug levels at 3 days and correlate with efficacy results.
  4. Examine early clinical, parasitologic, and clinical predictors of late treatment failure.
  5. Use the knowledge gained in Aims 1-3 to develop a molecular tool for a countrywide resistance surveillance system for antimalarial drugs.

Condition Intervention
Malaria
Drug: chloroquine
Drug: sulfadoxine-pyrimethamine
Drug: amodiaquine
Drug: amodiaquine+artesunate
Drug: amodiaquine+sulfadoxine-pyrimethamine
Drug: sulfadoxine-pyrimethamine+artesunate
Drug: artemether-lumefantrine
Drug: mefloquine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Characterization of Novel Molecular Tools for the Epidemiological Surveillance of Antimalarial Drug Resistance in Mali

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Early Treatment Failure (ETF, defined as: Development of danger signs or severe malaria on Day 1, 2, or 3, in the presence of parasitemia
  • Parasitemia on Day 2 higher than Day 0 count irrespective of axillary temperature
  • Parasitemia on Day 3 with axillary temperature ≥37.5°C
  • Parasitemia on Day 3 ≥ 25% of count on Day 0
  • Late Clinical Failure (LCF), defined as: Development of danger signs or severe malaria from Day 4 to Day 28 in the presence of parasitemia, without previously meeting any of the criteria of ETF
  • Presence of parasitemia and axillary temperature ≥37.5° C on any day from Day 4 to Day 28, without previously meeting any of the criteria of ETF
  • Late parasitological failure (LPF), defined as: Presence of parasitemia on Day 14 to Day 28 and axillary temperature <37.5°C without previously meeting any of the criteria of ETF or LCF
  • Adequate Clinical and Parasitological Response (ACPR), defined as: Absence of parasitemia on Day 28 irrespective of axillary temperature, without previously meeting any of the criteria of ETF, LCF or LPF

Secondary Outcome Measures:
  • Frequencies of dhfr, dhps, pfcrt and pfmdr1 P. falciparum genotypes and relationship with in vivo resistance to SP (dhfr and dhps), CQ, AQ, SP/AQ, AQ/AS, SP/AS, and MQ
  • Drug levels at 3 days and correlation with in vivo efficacy results

Estimated Enrollment: 1011
Study Start Date: July 2005
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   6 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 6-59 months
  • Absence of severe malnutrition (defined as a child whose weight-for-height is below 3 standard deviations of less than 70% of the median of World Health Organization (WHO) reference values, or who has symmetrical edema involving at least the feet)
  • A slide-confirmed infection with P. falciparum only (i.e. no mixed infections)
  • Initial parasite density between 2,000 and 200,000 asexual parasites per microliter.
  • Absence of general danger signs among children < 5 years (inability to drink or breastfeed; vomiting everything; recent history of convulsions; lethargy or unconsciousness; inability to sit or stand up) or other signs of severe and complicated falciparum malaria according to WHO definitions
  • Measured axillary temperature ≥ 37.5 °C
  • Ability to attend stipulated follow-up visits
  • Informed consent provided by parent/guardian
  • Absence of history of hypersensitivity reactions to any of the drugs being evaluated

Exclusion Criteria:

  • Aged < 6 or >59 months
  • Severe malnutrition (defined as a child whose weight-for-height is below 3 standard deviations of less than 70% of the median of WHO reference values, or who has symmetrical edema involving at least the feet)
  • No slide confirmed infection with P. falciparum or a mixed infection that includes a non P. falciparum species
  • Initial parasite density < 2,000 or > 200,000 asexual parasites per microliter.
  • Presence of general danger signs among children < 5 years (inability to drink or breastfeed; vomiting everything; recent history of convulsions; lethargy or unconsciousness; inability to sit or stand up) or other signs of severe and complicated falciparum malaria according to WHO definitions
  • Measured axillary temperature <37.5 °C
  • Inability to attend stipulated follow-up visits
  • Unwilling to provide informed consent provided by parent/guardian
  • History of hypersensitivity reactions to any of the drugs being evaluated
  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: NCT00127998

Locations
Mali
Faladje Missionary Dispensary
Faladje, Mali
Koro Health Center
Koro, Mali
Pongono Community Health Center
Pongono, Mali
Sponsors and Collaborators
Malaria Research and Training Center, Bamako, Mali
Investigators
Principal Investigator: Robert D. Newman, MD, MPH Centers for Disease Control and Prevention
Principal Investigator: Kassoum Kayentao, MD, MSPH Malaria Research and Training Center, Bamako, Mali
Principal Investigator: John Barnwell, PhD, MPH Centers for Disease Control and Prevention
Principal Investigator: Ogobara Doumbo, MD, PhD Malaria Research and Training Center, Bamako, Mali
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00127998     History of Changes
Other Study ID Numbers: CDC-NCID-4314
Study First Received: July 7, 2005
Last Updated: August 15, 2006
Health Authority: United States: Federal Government
Mali: Ministry of Health

Keywords provided by Centers for Disease Control and Prevention:
malaria
Plasmodium falciparum
drug resistance
antimalarials
genotype
treatment outcome

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Amodiaquine
Antimalarials
Chloroquine
Chloroquine diphosphate
Mefloquine
Pyrimethamine
Sulfadoxine
Artemether
Artesunate
Artemisinins
Sulfadoxine-pyrimethamine
Lumefantrine
Artemether-lumefantrine combination
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Amebicides
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 20, 2014