Efficacy of Artesunate-Mefloquine Combination Therapy in Trat Province, Thailand

Efficacy of Artesunate-Mefloquine Combination Therapy for the Treatment of Uncomplicated Falciparum Malaria in Trat Province, Thailand

The main purpose of this study is to compare artesunate-mefloquine combination therapy given for 2 and 3 days at the same total dose for the treatment of uncomplicated falciparum malaria.

Study Overview

• Status: Completed
• Conditions: Plasmodium Falciparum Malaria
• Intervention / Treatment: Drug: Artesunate; Drug: Artesunate; Drug: Mefloquine; Drug: Mefloquine

Detailed Description

This will be a randomized, open-label comparison of two versus three days artesunate-mefloquine treatment in patients with uncomplicated falciparum malaria. Primary endpoints will be 63-day parasitological cure rates in the 2 treatment groups. Secondary endpoints will be parasitological failure rates at each of the weekly follow-up visits to Day 56, occurence of treatment-emergent adverse events on days 0, 1 and 2, mefloquine blood concentrations on days 7, 14 and 28, and in vitro drug sensitivity profiles for parasite isolates as measured by inhibitory concentrations. Genotyping of parasites for known markers of drug resistence will be performed.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Trat
    • Borai, Khaosaming and Muang districts, Trat, Thailand, 23000
      • Vector Borne Diseases Control Units (VBDC, malaria clinics)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 68 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 5 to 70 years inclusive. If aged < 18 years the subject must have a parent or guardian in attendance.
2. Asexual stages of P. falciparum parasites in a thick or thin blood film with no other visible plasmodial species.
3. Willing to give informed consent. Parents or guardians of children and adolescents must agree to give informed consent. Assent is necessary in addition to parental informed consent.
4. Able to tolerate oral therapy.
5. Willing to attend follow-up appointments and undergo study procedures.

Exclusion Criteria:

1. History of anti-malarial drug use within the past two weeks or mefloquine (MQ) use within 4 weeks.
2. Bleeding tendency (by history or based on medical records).
3. Severe/complicated malaria as determined by the investigator (coma or seizures, pulmonary edema, shock, renal failure, jaundice, severe anemia, spontaneous bleeding, hyperparasitemia (>5% RBCs infected), or prostration).
4. History of allergy to or intolerance of study medications.
5. Mixed malaria infection by Giemsa stain.
6. Any other condition that in the opinion of the study investigator warrants parenteral antimalarial treatment.
7. Pregnant woman or nursing mother

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; 2-day oral treatment with: Artesunate 6mg/kg at 0 and 24 hours Mefloquine 25 mg/kg total dose split into 2 doses of 15 mg/kg at 0 hours and and 10 mg/kg given 6-24 hours later Primaquine 0.5 mg/kg single dose at 24 hours	Drug: Artesunate; 6 mg/kg/day for 2 days (total dose 12 mg/kg); Drug: Artesunate; 4 mg/kg/day for 3 days; Drug: Mefloquine; 15mg/kg at T=0 and 10 mg/kg 6-24 hours later; Drug: Mefloquine; 8 mg/kg daily for 3 days
Active Comparator: 2; 3 days oral treatment with: Artesunate 4 mg/kg/day for 3 days Mefloquine 8 mg/kg/day for 3 days Primaquine 0.5 mg/kg single dose at 24 hours	Drug: Artesunate; 6 mg/kg/day for 2 days (total dose 12 mg/kg); Drug: Artesunate; 4 mg/kg/day for 3 days; Drug: Mefloquine; 15mg/kg at T=0 and 10 mg/kg 6-24 hours later; Drug: Mefloquine; 8 mg/kg daily for 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determination of parasitological cure rate of directly observed antimalarial therapy	63 days from initiation of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Parasitological cure rates	Weekly to Day 56
Occurence of treatment-emergent adverse events	3 days
In vitro drug sensitivity profile for individual parasite isolates	Baseline
Mefloquine whole blood concentrations	28 days

Collaborators and Investigators

• Sponsor: Armed Forces Research Institute of Medical Sciences, Thailand
• Investigators: Principal Investigator: Wichai - Satimai, M.D., D.T.M. & H., Bureau of Vector-Borne Disease, Department of Disease Control, Ministry of Public Health; Principal Investigator: Mark M. Fukuda, M.D., Dept. of Immunology and Medicine, AFRIMS

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: January 26, 2011
• First Submitted That Met QC Criteria: August 6, 2012
• First Posted (Estimate): August 7, 2012

Study Record Updates

• Last Update Posted (Estimate): August 7, 2012
• Last Update Submitted That Met QC Criteria: August 6, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Plasmodium Falciparum; Thailand; Artesunate; Mefloquine; Uncomplicated Plasmodium Falciparum malaria
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate; Mefloquine
• Other Study ID Numbers: WRAIR-1327