In Vivo and In Vitro Efficacy of Artemisinin Combination Therapy

NCT01976780 | Completed Phase 4

• 1 other identifier: WRAIR1935
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to assess the degree of artemisinin resistance in adult and pediatric subjects presenting with uncomplicated falciparum malaria in Western Kenya. The study treatments will be Artemether Lumefantrine (AL) and Artesunate Mefloquine (ASMQ).

Conditions

Malaria

Keywords

Malaria; P. falciparum mono infection; Early Treatment Failure; Late Treatment Failure

Outcome Measures

Primary Outcomes (1)

• Parasitological clearance rates by microscopy

  Clearance rates for the first 72 hour period after first ACT dose in patients with uncomplicated P. falciparum malaria

  72 hours

Secondary Outcomes (7)

• Parasitological clearance rates by quantitative Polymerase Chain Reaction (PCR)

  72 hours

• PCR-adjusted treatment efficacy of AL and AS/MQ

  42 days

• Antimalarial drug sensitivity responses and molecular genotyping

  42 days

• Identify common specific genetic determinants of artemisinin resistance derived from parasite populations

  42 days

• Gametocyte carriage in patients with uncomplicated malaria after treatment

  42 days

Other Outcomes (3)

• Parasite clearance rates and immune response in semi-immune population

  42 days

• Production of microbiocidal molecules

  42 days

• Acute cytokine response

  42 days

Study Arms (2)

AS/MQ

ACTIVE COMPARATOR

Treatment of P.falciparum mono-infection with 4 mg/kg of Artesunate daily for three days followed by 25mg/kg of Mefloquine split over two days.

Drug: Artesunate; Drug: Mefloquine

AL

ACTIVE COMPARATOR

Treatment of P. falciparum mono-infection with Artemether Lumefantrine administered at the standard dosage according to pre-defined weight bands (5-14 kg: 1 tablet; 15-24 kg: 2 tablets; 25-34 kg: 3 tablets; and \> 34 kg: 4 tablets) given twice a day for 3 days.

Drug: Artemether Lumefantrine

Interventions

Artesunate DRUG

Also known as: AS

AS/MQ

Artemether Lumefantrine DRUG

Also known as: AL

AL

Mefloquine DRUG

Also known as: MQ

AS/MQ

Eligibility Criteria

• Age: 6 Months - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult/child aged between 6 months and 65 years inclusive (minimum weight 11kg), presenting with a measured temperature of ≥37.5 C, or history of fever within 24 hours prior to presentation
• Mono-infection with Plasmodium falciparum
• Baseline parasitemia of 2000 - 200,000 asexual parasites/µl
• Ability to provide informed consent
• Willingness and ability to comply with the study protocol for the duration of the study
• Willingness to remain in the hospital for 3 days

You may not qualify if:

• Presence of signs of severe malaria as defined by WHO
• Presence of severe anemia, defined as hemoglobin level below 6 g/dl
• Presence of mixed Plasmodium infection, or mono-infection of non-falciparum Plasmodium
• Inability to take oral medication
• History of allergy or contraindications to the study treatments
• Lactating or pregnant females
• Any condition that the investigator feels will result in an unfavorable outcome should the potential subject participate in the study

Sponsors & Collaborators

• Global Emerging Infections Surveillance and Response System: lead
• United States Army Medical Unit - Kenya: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

Walter Reed Project, Kombewa Clinic

Kisumu, Kenya

Location

Related Publications (1)

• Odhiambo G, Bergmann-Leitner E, Maraka M, Wanjala CNL, Duncan E, Waitumbi J, Andagalu B, Jura WGZO, Dutta S, Angov E, Ogutu BR, Kamau E, Ochiel D. Correlation Between Malaria-Specific Antibody Profiles and Responses to Artemisinin Combination Therapy for Treatment of Uncomplicated Malaria in Western Kenya. J Infect Dis. 2019 May 24;219(12):1969-1979. doi: 10.1093/infdis/jiz027.

  PMID: 30649381 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Artesunate; Artemether, Lumefantrine Drug Combination; Mefloquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Artemether; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• James F Cummings, MD

  GEIS

  STUDY CHAIR

• Ben Andagalu, MD

  Kenya Medical Research Institute/Walter Reed Project

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2013
• First Posted: November 6, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 11, 2017

Record last verified: 2017-05

Locations

KE (1)