Antimalarial Drug Resistance in Mali
This study has been completed.
Sponsor:
Collaborator:
Malaria Research and Training Center, Bamako
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
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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:
- 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.
- 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
- Measure drug levels at 3 days and correlate with efficacy results.
- Examine early clinical, parasitologic, and clinical predictors of late treatment failure.
- 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:
MedlinePlus related topics:
Malaria
Drug Information available for:
Chloroquine phosphate
Chloroquine
Pyrimethamine
Chloroquine sulfate
Chloroquine hydrochloride
Mefloquine hydrochloride
Artemether
Lumefantrine
U.S. FDA Resources
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
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
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 |
| Principal Investigator: | John Barnwell, PhD, MPH | Centers for Disease Control and Prevention |
| Principal Investigator: | Ogobara Doumbo, MD, PhD | Malaria Research and Training Center, Bamako |
More Information
Publications:
WHO. Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Geneva: World Health Organization, 2003
| 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 June 17, 2013