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

Sponsor

Armed Forces Research Institute of Medical Sciences, Thailand (Other)

Overall Status

Completed

CT.gov ID

NCT01659281

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Plasmodium Falciparum Malaria	Drug: Artesunate Drug: Artesunate Drug: Mefloquine Drug: Mefloquine	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2007

Actual Primary Completion Date :

May 1, 2008

Actual Study Completion Date :

May 1, 2012

Arms and Interventions

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: Mefloquine 15mg/kg at T=0 and 10 mg/kg 6-24 hours later
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 4 mg/kg/day for 3 days Drug: Mefloquine 8 mg/kg daily for 3 days

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: Mefloquine

15mg/kg at T=0 and 10 mg/kg 6-24 hours later

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

4 mg/kg/day for 3 days

Drug: Mefloquine

8 mg/kg daily for 3 days

Outcome Measures

Primary Outcome Measures

Determination of parasitological cure rate of directly observed antimalarial therapy [63 days from initiation of treatment]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 5 to 70 years inclusive. If aged < 18 years the subject must have a parent or guardian in attendance.
Asexual stages of P. falciparum parasites in a thick or thin blood film with no other visible plasmodial species.
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.
Able to tolerate oral therapy.
Willing to attend follow-up appointments and undergo study procedures.

Exclusion Criteria:

History of anti-malarial drug use within the past two weeks or mefloquine (MQ) use within 4 weeks.
Bleeding tendency (by history or based on medical records).
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).
History of allergy to or intolerance of study medications.
Mixed malaria infection by Giemsa stain.
Any other condition that in the opinion of the study investigator warrants parenteral antimalarial treatment.
Pregnant woman or nursing mother

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vector Borne Diseases Control Units (VBDC, malaria clinics)	Borai, Khaosaming and Muang districts	Trat	Thailand	23000

Sponsors and Collaborators

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