Assessment of the ability of artemether-lumefantrine and dihydroartemisinin – piperaquine to treat simple malaria in children in Uganda

• Register: ISRCTN
• Last refreshed on: 3 February 2020
• Main ID: ISRCTN15793046
• Date of registration: 20/10/2015
• Prospective Registration: No
• Primary sponsor: Uganda Ministry of Health
• Public title: Assessment of the ability of artemether-lumefantrine and dihydroartemisinin – piperaquine to treat simple malaria in children in Uganda
• Scientific title: Efficacy of artemether-lumefantrine and dihydroartemisinin – piperaquine for treatment of uncomplicated malaria in children in Uganda
• Date of first enrolment: 15/09/2015
• Target sample size: 600
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN15793046
• Study type: Interventional
• Study design: Multi-centre single-blinded randomised parallel trial. (Treatment)
• Phase: Phase IV

Countries of recruitment

Uganda

Contacts

• Name: Adoke Yeka

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age 6 – 59 months
2. Fever (> 37.5ºC axillary) or history of fever in the previous 24 hours
3. Ability to participate in 42-day follow-up (patient has easy access to health unit)

Exclusion criteria:
1. Weight < 5 kg
2. History of serious side effects to study medications
3. Concomitant febrile illness or presence of intercurrent illness or any condition (cardiac, renal, hepatic diseases) which would place the subject at undue risk or interfere with the results of the study
4. Treatment with antimalarial drugs (ACTs) already started and ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocisti carini pneumonia in children born to HIV+ women.
5. Severe malnutrition (defined as weight for height <70% of the median NCHS/WHO reference)
6. Danger signs or evidence of severe malaria:
6.1. Unarousable coma (if after convulsion, > 30 min)
6.2. Recent convulsions (1-2 within 24 h)
6.3. Altered consciousness (confusion, delirium, psychosis, coma)
6.4. Lethargy
6.5. Unable to drink or breast feed
6.6. Vomiting everything
6.7. Unable to stand/sit due to weakness
6.8. Severe anemia (Hb < 5.0 gm/dL)
6.9. Respiratory distress (labored breathing at rest)
6.10. Jaundice
7. Severe malnutrition (defined as a child whose growth standard is below –3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm).
8. Regular medication, which may interfere with antimalarial pharmacokinetic
9. History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s)


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Malaria
Infections and Infestations
Malaria

Intervention(s)

Subjects who meet the selection criteria will be randomized to treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) and will be followed for 42 days. Repeat evaluations will be performed on days 1, 2, 3, 7, 14, 21, 28, 35 and 42 (and any unscheduled days) and will include assessment for the occurrence of adverse events.

Primary Outcome(s)

1. Risk of parasitological treatment failure (Early Treatment Failure (ETF)
2. Late Parasitological Failure (LPF)
3. Late Clinical Failure (LCF))

All assessed after 42 days of follow-up unadjusted and adjusted by genotyping to distinguish recrudescence from new infections. Risks will be estimated using the Kaplan-Meier product limit formula based on a modified intention-to-treat analysis.

Secondary Outcome(s)

1. Prevalence of fever (defined as both subjective fever in the previous 24 hours and measured axillary temperature greater than 37.5ºC) on follow-up days 1, 2, and 3
2. Prevalence of parasitemia (proportion of patients with malaria parasites in their blood) on follow-up days 1, 2 and 3
3. Parasite clearance time. Defined as the number (n) and the proportion (%) of patients with a positive parasite count on day 2 and 3 as well as the number (N) of patients evaluated on that day shall be estimated. The parasite clearance rate and initial parasite clearance lag phase duration shall be estimated by modelling the log (parasitemia) time profile using the PCT calculator
4. Change in mean hemoglobin from day 0 to 42 (or day of rescue therapy for patients classified as LCF or LPF), measured from blood samples
5. Prevalence of gametocytemia and gametocyte density in the blood on follow-up days 1, 2, 3, 7, 14, 21, 28, 35 and 42
6. Proportion of patients experiencing any serious adverse event in each treatment group during the 42-day follow-up period (both including and excluding patients classified as ETF or LCF, as recurrent malaria can be confounding)
7. Proportion of patients with adverse events of moderate or greater severity, at least possibly related to the study medications, excluding patients requiring quinine therapy during follow up days.
8. Change in the prevalence of molecular markers in the blood, associated with drug resistance (proportion of patients who fail treatment with K 13 mutants) from day 0 to the day of recurrent parasitemia

Secondary ID(s)

Protocol version 1.2

Source(s) of Monetary Support

The World Bank, Ministry of Health, Uganda

Ethics review

Status:
Approval date:
Contact:

1. Makerere University School of Public Health Research Higher Degrees Research and Ethics Committee, 10/06/2015, ref: 205 2. Uganda National Council of Science and Technology, 26/06/2015, ref: HS 1356

Results

• Results available: Yes
• Date Completed: 01/09/2017