Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
NA
1011 participants
INTERVENTIONAL
2005-07-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Given the above, 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. Such methods would help malaria control and prevention programs in guiding national treatment recommendations and policies. Integrating laboratory expertise, analytic methods based on population genetics, and more traditional methods of surveillance for anti-malarial drug resistance (e.g. in vivo drug efficacy studies) and networking with national and international partners will result in a multidisciplinary, geographically diverse team approach to assessing and monitoring drug resistant malaria, as well as developing and validating molecular methods. This type of effort will greatly assist in maximizing the useful life span of antimalarial drugs and in providing evidence-based guidance for drug policy decisions.
Specific Aims:
1. Prospectively measure the in vivo response of P. falciparum malaria in Mali to CQ, SP, AQ, SP/AQ in combination, AQ/artesunate (AS) in combination, SP/AS, and artemether-lumefantrine (Co-artem). In one site with preliminary data showing a high rate of P. falciparum resistance to MQ, MQ will also be tested.
2. Measure the frequencies of dihydrofolate reductase (dhfr), dihydropteroate synthetase (dhps), P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multi-drug resistant (pfmdr 1) genotypes and establish their relationship with in vivo resistance to SP (dhfr and dhps), CQ, AQ, SP/AQ, AQ/AS, SP/AS, and MQ.
3. Measure drug levels at 3 days and correlate with in vivo 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 SP, AQ, and MQ.
Study Design:
The study will entail two consecutive years of prospective 28 day in vivo drug efficacy studies carried out during the rainy season in three different malaria transmission sites: Koro (rural town with 71% of resistance to MQ at a lower dose of 15 mg/kg), Pongono (rural town with little exposure to antimalarials) and Faladje (rural village with \> 30% of chloroquine resistance). Children aged 6-59 months with clinical symptoms consistent with malaria will be enrolled in the study after screening for fever (axillary temperature \>=37.5 C) and malaria asexual parasites identified by microscopic examination of thick blood films.
Blood spotted onto filter papers will be collected prior to treatment and during follow up. These filter paper samples will be used for the molecular detection of drug resistance-conferring gene polymorphisms as well as the HPLC detection and quantification of the respective drugs and their relevant metabolites. In vivo data interpretation will be done using the WHO 28-day protocol (WHO, 2003) and molecular markers will be used for the determination of the genotype resistance index (GRI). Venous blood will be collected at enrollment and at the time of in vivo failure to measure in vitro drug efficacy and cryopreserve parasites to search for novel molecular markers to new antimalarial drugs.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
chloroquine
sulfadoxine-pyrimethamine
amodiaquine
amodiaquine+artesunate
amodiaquine+sulfadoxine-pyrimethamine
sulfadoxine-pyrimethamine+artesunate
artemether-lumefantrine
mefloquine
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
6 Months
59 Months
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Malaria Research and Training Center, Bamako, Mali
OTHER
Centers for Disease Control and Prevention
FED
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Robert D. Newman, MD, MPH
Role: PRINCIPAL_INVESTIGATOR
Centers for Disease Control and Prevention
Kassoum Kayentao, MD, MSPH
Role: PRINCIPAL_INVESTIGATOR
Malaria Research and Training Center, Bamako, Mali
John Barnwell, PhD, MPH
Role: PRINCIPAL_INVESTIGATOR
Centers for Disease Control and Prevention
Ogobara Doumbo, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Malaria Research and Training Center, Bamako, Mali
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Faladje Missionary Dispensary
Faladié, , Mali
Koro Health Center
Koro, , Mali
Pongono Community Health Center
Pongono, , Mali
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
WHO. Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Geneva: World Health Organization, 2003
Plowe CV. Monitoring antimalarial drug resistance: making the most of the tools at hand. J Exp Biol. 2003 Nov;206(Pt 21):3745-52. doi: 10.1242/jeb.00658.
Wernsdorfer WH, Noedl H. Molecular markers for drug resistance in malaria: use in treatment, diagnosis and epidemiology. Curr Opin Infect Dis. 2003 Dec;16(6):553-8. doi: 10.1097/00001432-200312000-00007.
Djimde A, Doumbo OK, Steketee RW, Plowe CV. Application of a molecular marker for surveillance of chloroquine-resistant falciparum malaria. Lancet. 2001 Sep 15;358(9285):890-1. doi: 10.1016/S0140-6736(01)06040-8. No abstract available.
Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Coulibaly D, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med. 2001 Jan 25;344(4):257-63. doi: 10.1056/NEJM200101253440403.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CDC-NCID-4314
Identifier Type: -
Identifier Source: org_study_id