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

NCT01082705 | Completed Phase 3

• 1 other identifier: IMPACT TZ IV2010
• Study Type: interventional
• Target: 323
• Locations: 1 country
• Sites: 1

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.

Conditions

P. Falciparum Malaria

Keywords

malaria; treatment; artemisinin combination therapy; Tanzania; P. falciparum malaria in children age 6-59 months

Outcome Measures

Primary Outcomes (1)

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

  42 days

Secondary Outcomes (1)

• Hematologic response to treatment measured as mean change in hemoglobin concentration from Day 0 to Day 42

  42 days

Study Arms (2)

Artemether-lumefantrine

ACTIVE COMPARATOR

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

Dihydroartemisinin-piperaquine

EXPERIMENTAL

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

Interventions

artemether-lumefantrine DRUG

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

Also known as: Coartem Novartis

Artemether-lumefantrine

Dihydroartemisinin-piperaquine DRUG

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

Dihydroartemisinin-piperaquine

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead

Study Sites (1)

Miono Health Center

Bagamoyo, Tanzania

Location

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Julie R Gutman, MD MSc

  Centers for Disease Control and Prevention

  STUDY DIRECTOR

• S. Patrick Kachur, MD MPH

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Epidemiologist, Malaria Branch

Study Record Dates

• First Submitted: March 8, 2010
• First Posted: March 9, 2010
• Study Start: April 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: January 31, 2012

Record last verified: 2012-01

Locations

TA (1)