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Plasmodium Falciparum Clearance Rates in Response to Artesunate in Eastern Cambodia

This study has been completed.
Sponsor:
Collaborator:
National Center for Parasitology, Entomology, and Malaria Control, Ministry of Health
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01240603
First received: November 11, 2010
Last updated: October 23, 2014
Last verified: September 2013
  Purpose

Plasmodium falciparum parasite clearance rates (PCRs) after oral artesunate treatment of patients with uncomplicated malaria were recently found to be significantly slower in Pailin (Western Cambodia) compared to Wang Pha (Eastern Thailand). This difference in PCRs has been attributed to different histories of artesunate drug pressure in the two areas. In Pailin, artesunate monotherapy has been used inappropriately for 30 years and is hypothesized to have selected for artemisinin-resistant parasites (slow PCRs). To investigate the potential contribution of human factors to the artemisinin resistance phenotype, we have identified a study site in Eastern Cambodia where artemisinin-resistant parasites are not believed to be present. The main aims of this study are to 1) determine whether the artemisinin resistance phenotype (i.e., a half-life longer than the 2-hour half-life observed in Wang Pha) is present in Eastern Cambodia, 2) determine whether hemoglobin E affects parasite clearance rates in vivo, 3) determine whether age-associated acquired immunity affects parasite clearance rates in vivo, and 4) identify parasite-heritable traits that are associated with slow parasite clearance rates in vivo. To meet these aims, we are conducting a prospective, longitudinal study to recruit Cambodian residents of Lumphat District in Ratanakiri Province who complain of fever and/or symptoms of malaria. Patients diagnosed with uncomplicated malaria will be treated with weight-based doses of artesunate given orally each day for 3 days followed by mefloquine given orally for 2 days. During this time, finger prick blood smears will be obtained every 6 hours until parasite density is zero. From these data, we will estimate parasite clearance rates using a half-life parameter. We will also collect parasitized red blood cell samples from malaria patients prior to antimalarial drug administration. These parasites will be tested in short-term in vitro culture experiments to determine their susceptibility to artemisinins and other antimalarial drugs....


Condition
Malaria

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Plasmodium Falciparum Clearance Rates in Response to Artesunate in Eastern Cambodia

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 415
Study Start Date: October 2010
Estimated Study Completion Date: September 2013
Detailed Description:

Plasmodium falciparum parasite clearance rates (PCRs) after oral artesunate treatment of patients with uncomplicated malaria were recently found to be significantly slower in Pailin (Western Cambodia) compared to Wang Pha (Eastern Thailand). This difference in PCRs has been attributed to different histories of artesunate drug pressure in the two areas. In Pailin, artesunate monotherapy has been used inappropriately for 30 years and is hypothesized to have selected for artemisinin-resistant parasites (slow PCRs). To investigate the potential contribution of human factors to the artemisinin resistance phenotype, we have identified a study site in Eastern Cambodia where artemisinin-resistant parasites are not believed to be present. The main aims of this study are to 1) determine whether the artemisinin resistance phenotype (i.e., a half-life longer than the 2-hour half-life observed in Wang Pha) is present in Eastern Cambodia, 2) determine whether hemoglobin E affects parasite clearance rates in vivo, 3) determine whether age-associated acquired immunity affects parasite clearance rates in vivo, and 4) identify parasite-heritable traits that are associated with slow parasite clearance rates in vivo. To meet these aims, we are conducting a prospective, longitudinal study to recruit Cambodian residents of Lumphat District in Ratanakiri Province who complain of fever and/or symptoms of malaria. Patients diagnosed with uncomplicated malaria will be treated with weight-based doses of artesunate given orally each day for 3 days followed by mefloquine given orally for 2 days. During this time, finger prick blood smears will be obtained every 6 hours until parasite density is zero. From these data, we will estimate parasite clearance rates using a half-life parameter. We will also collect parasitized red blood cell samples from malaria patients prior to antimalarial drug administration. These parasites will be tested in short-term in vitro culture experiments to determine their susceptibility to artemisinins and other antimalarial drugs.

  Eligibility

Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Age 2 to 65 years, inclusive

Uncomplicated P. falciparum malaria.

Tympanic temperature greater than or equal to 37.5 degree C or history of fever within the last 24 h.

P. calciparum asexual parasite density 10,000 200,000/microL, Inclusive.

Willingness to allow the storage of blood samples collected as part of the study.

Willingness and ability of the patient/guardians to comply with the protocol for the duration of the study.

EXCLUSION CRITERIA:

Severe malaria: diminished consciousness, respiratory distress, severe prostration, anuria, jaundice, hemoglobinuria, repetitive vomiting, or cessation of eating and drinking.

Non-malaria etiology of febrile illness (e.g., respiratory tract infection) evident on clinical examination.

Hematocrit < 25 percent

Treatment of present symptoms with an artemisinin compound or artemisinin-based combination therapy within the previous 7 days.

Pregnancy or breastfeeding

History or allergy or known contraindication to artemisinins or piperaquine

Splenectomy.

  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: NCT01240603

Locations
Cambodia
National Center for Parasitology, Entomology, and Malaria Controk, Ministry of H
Phnom Penh, Cambodia
Sponsors and Collaborators
National Center for Parasitology, Entomology, and Malaria Control, Ministry of Health
Investigators
Principal Investigator: Rick M Fairhurst, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT01240603     History of Changes
Other Study ID Numbers: 999911017, 11-I-N017
Study First Received: November 11, 2010
Last Updated: October 23, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Artemisinin
Malaria
Drug Resistance
Hemoglobin E

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections

ClinicalTrials.gov processed this record on November 24, 2014