Extended Duration Artemether-lumefantrine Treatment for Malaria in Children

• Register: ClinicalTrials.gov
• Last refreshed on: 31 October 2022
• Main ID: NCT03453840
• Date of registration: 22/12/2017
• Prospective Registration: Yes
• Primary sponsor: University of California, San Francisco
• Public title: Extended Duration Artemether-lumefantrine Treatment for Malaria in Children EXALT
• Scientific title: Extended Duration Artemether-lumefantrine Treatment for Malaria in Children
• Date of first enrolment: February 19, 2018
• Target sample size: 305
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03453840
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Uganda

Contacts

• Name: Francesca Aweeka, Pharm. D
• Affiliation: University of California, San Francisco

• Name: Sunil Parikh, M.D., MPH
• Affiliation: Yale University School of Public Health

Key inclusion & exclusion criteria

Inclusion Criteria:

1, All participants:

1. Residency within 60 km of the study clinics either at TDH or at MGH

2. Agreement to come to clinic for all follow-up clinical and PK evaluations

3. Provision of informed consent

4. Weight =6 kg

5. Presentation with uncomplicated falciparum malaria as indicated by positive smear for
malaria parasites along with clinical evidence of infection (fever or history of fever
in the past 24 hours)

6. Willingness to undergo intensive PK sampling and/or population PK sampling during
episode(s) of malaria.

2 HIV-infected participants:

1. Confirmed HIV infection (positive rapid HIV test to be confirmed by Western Blot or
HIV RNA after enrollment)

2. On stable EFV-based ART for at least 10 days prior to enrollment

3. Age 3 years to 10 years

3 HIV-uninfected participants:

1. Confirmed HIV negative test (negative rapid HIV test to be confirmed by Western Blot
or HIV RNA after enrollment)

2. Age 6 months to 10 years

Exclusion Criteria:

1. History of significant comorbidities such as malignancy, active tuberculosis or other
World Health Organization (WHO) stage 4 disease

2. Current infection with non-P. falciparum species

3. Receipt of any medications known to affect CYP450 metabolism (except ART) within 14
days of study enrollment (see 4.2.2)

4. Hemoglobin < 7.0 g/dL

5. For the population PK study, prior treatment for malaria within 14 days of enrollment

6. For the intensive PK study, prior treatment for malaria within 28 days of enrollment

7. Signs or evidence of complicated malaria, defined as unarousable coma or any two of
the following symptoms: Recent febrile convulsions, altered consciousness, lethargy,
unable to drink, unable to stand/sit due to weakness, severe anemia (Hb < 5.0 gm/dL),
respiratory distress, jaundice (see Appendix D)

8. History of toxicity to AL

The following medications are disallowed within 3 weeks prior to receiving study drug:

- Carbamazepine

- Clarithromycin

- Erythromycin (oral)

- Ketoconazole

- Phenobarbital

- Phenytoin

- Rifabutin

- Rifampin

- Halofantrine

- Any other medication known to significantly affect CYP450 metabolism.

- Grapefruit juice should be avoided during the study due to its potential effects on
CYP3A4.



Age minimum: 6 Months
Age maximum: 10 Years
Gender: All

Health Condition(s) or Problem(s) studied

Uncomplicated Plasmodium Falciparum Malaria

Intervention(s)

Drug: Artemether-lumefantrine

Primary Outcome(s)

Area under the plasma concentration versus time curve (AUC) for all drug analytes [Time Frame: Study day 0-day21]

Recurrent malaria following treatment by day 42 (recrudescence or new infection) [Time Frame: up to study day 42]

Secondary Outcome(s)

Safety of 5-day vs 3-day AL regimens evaluated via graded toxicity [Time Frame: study day 0-42]

Height-for-age (HFA) associations with PK [Time Frame: study day 0]

Weight-for-height (WFH) associations with PK [Time Frame: study day 0]

Prevalence of gametocytemia following treatment in 3-day vs 5-day AL regimens determined by thick blood smears [Time Frame: study day 0-42]

Relationship between drug resistance and treatment failure [Time Frame: study day 0-42]

Weight-for-age (WFA) associations with PK [Time Frame: study day 0]

Diagnostic sensitivity of LAMP, HS-RDT, and microscopy for the detection of recurrent parasitemia [Time Frame: study day 0-42]

Metabolomic measurements in HIV infected vs HIV uninfected children [Time Frame: study day 0-42]

Secondary ID(s)

17-22578

2R01HD068174-06A1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Infectious Diseases Research Collaboration, Uganda

Yale University

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)