Assessing the Efficacy of Artemisinin Combination Therapies for Treatment of Uncomplicated Malaria Infection in Children

Sponsor

Centers for Disease Control and Prevention (U.S. Fed)

Overall Status

Completed

CT.gov ID

NCT01082705

Collaborator

(none)

323

Enrollment

Location

Arms

Duration (Months)

23.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Following the rapid development of significant drug resistance to both chloroquine and sulfadoxine-pyrimethamine (the first line therapy in Tanzania from 2001 -2006), artemether- lumefantrine (Coartem or AL) was adopted as first line therapy in Tanzania in 2006. Now that this drug has been widely used for some time, the investigators propose to conduct an antimalarial efficacy trial to monitor the effectiveness of this therapy, to determine if this drug remains efficacious, or if significant resistance has emerged, in which case a new antimalarial strategy will need to be contemplated. The investigators hypothesize that the efficacy of Artemether-lumefantrine remains high, and that the other artemisinin combination therapies will be equally efficacious.

Children 6-59 months of age with symptomatic malaria will be randomly assigned to be treated with either artemether + lumefantrine (Coartem) or dihydroartemisinin-piperaquine (Duo-Cotecxin or Artekin). Clinical, parasitologic, and hematologic parameters will be monitored over a 42-day follow-up period and will be used to evaluate drug efficacy.

Condition or Disease	Intervention/Treatment	Phase
P. Falciparum Malaria	Drug: artemether-lumefantrine Drug: Dihydroartemisinin-piperaquine	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

323 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Impact Tanzania in Vivo Efficacy 2010: Assessing the Efficacy of Artemisinin Combination Therapies for Treatment of Uncomplicated Malaria Infection in Children Aged 6-59 Months

Study Start Date :

Apr 1, 2010

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Artemether-lumefantrine Artemether-lumefantrine (Coartem; Novartis) administered twice daily for three days as tablets containing 20 mg of artemether plus 120 mg of lumefantrine at a dosage of: 1 tablet for patients weighing 5-14 kg, 2 tablets for patients weighing 15-24 kg, 3 tablets for patients weighing 25-34 kg, 4 tablets for patients weighing 35 kg or more	Drug: artemether-lumefantrine administered twice daily for three days as tablets containing 20 mg of artemether plus 120 mg of lumefantrine at a dosage of: 1 tablet for patients weighing 5-14 kg, 2 tablets for patients weighing 15-24 kg, 3 tablets for patients weighing 25-34 kg, 4 tablets for patients weighing 35 kg or more Other Names: Coartem Novartis
Experimental: Dihydroartemisinin-piperaquine Dihydroartemisinin-piperaquine administered once daily for 3 days as tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine at a total dosage of 6.4 mg/kg of dihydroartemisinin and 51.2 mg/kg of piperaquine divided equally between the three days	Drug: Dihydroartemisinin-piperaquine once daily for 3 days as tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine at a total dosage of 6.4 mg/kg of dihydroartemisinin and 51.2 mg/kg of piperaquine divided equally between the three days

Arm

Intervention/Treatment

Active Comparator: Artemether-lumefantrine

Artemether-lumefantrine (Coartem; Novartis) administered twice daily for three days as tablets containing 20 mg of artemether plus 120 mg of lumefantrine at a dosage of: 1 tablet for patients weighing 5-14 kg, 2 tablets for patients weighing 15-24 kg, 3 tablets for patients weighing 25-34 kg, 4 tablets for patients weighing 35 kg or more

Drug: artemether-lumefantrine

administered twice daily for three days as tablets containing 20 mg of artemether plus 120 mg of lumefantrine at a dosage of: 1 tablet for patients weighing 5-14 kg, 2 tablets for patients weighing 15-24 kg, 3 tablets for patients weighing 25-34 kg, 4 tablets for patients weighing 35 kg or more

Other Names:

Coartem Novartis

Experimental: Dihydroartemisinin-piperaquine

Dihydroartemisinin-piperaquine administered once daily for 3 days as tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine at a total dosage of 6.4 mg/kg of dihydroartemisinin and 51.2 mg/kg of piperaquine divided equally between the three days

Drug: Dihydroartemisinin-piperaquine

once daily for 3 days as tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine at a total dosage of 6.4 mg/kg of dihydroartemisinin and 51.2 mg/kg of piperaquine divided equally between the three days

Outcome Measures

Primary Outcome Measures

42-day polymerase chain reaction (PCR)-adjusted parasitological cure of P. falciparum parasitemia [42 days]

Secondary Outcome Measures

Hematologic response to treatment measured as mean change in hemoglobin concentration from Day 0 to Day 42 [42 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 59 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 6-59 months
Axillary temperature ≥ 37.5º C or history of fever in the past 48 hours
Weight ≥ 5.0 kg
Slide-confirmed infection with P. falciparum, with parasitemia 2,000-200,000 asexual forms per μl
Live within the boundaries of the officially recognized catchment area of Miono Health Center.
Caregiver agrees to all blood draws and return visits.

Exclusion Criteria:

General danger signs or symptoms of severe malaria
Signs or symptoms of severe malnutrition, defined as weight-for-age ≤ 3 standard deviations below the mean (National Center for Health Statistics [NCHS]/World Health Organization [WHO] normalized reference values)
Slide confirmed infection with any other Plasmodium spp. besides falciparum or mixed plasmodium infection
Severe anemia, defined as Hb < 5 g/dl
Known hypersensitivity to any of the drugs being tested
Presence of febrile conditions caused by diseases other than malaria
Serious or chronic medical condition (heart failure, sickle cell disease).
Plan to travel or leave the area within the next 3 months.
Have been treated for malaria in the 2 weeks prior to enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Miono Health Center	Bagamoyo		Tanzania

Sponsors and Collaborators

Centers for Disease Control and Prevention

Investigators

Study Director: Julie R Gutman, MD MSc, Centers for Disease Control and Prevention
Principal Investigator: S. Patrick Kachur, MD MPH, Centers for Disease Control and Prevention