Pharmacokinetic Study of IV Artesunate to Treat Children With Severe Malaria

NCT ID: NCT05750459

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-29
• Study Completion Date: 2025-04-01

Brief Summary

This clinical study is a phase 4, single-site, open-label pharmacokinetic (PK) study of IV artesunate in up to 100 Ugandan children 6 months-14 years of age who are diagnosed with severe malaria according to standardized World Health Organization (WHO) criteria (any P. falciparum parasitemia and the presence of danger signs). Participants will receive the standard of care IV artesunate for initial treatment of severe malaria per WHO guidelines: children weighing <20 kg should receive 3.0 mg/kg/dose compared to children weighing =20 kg who should receive 2.4 mg/kg/dose, at times 0, 12, 24, 48 and 72 hours (WHO 2015). Parenteral treatment will be administered for a minimum of 24 hours (irrespective of the patient's ability to tolerate oral medication earlier), after which patients will be evaluated clinically and assessed for ability for oral intake of antimalarials. Children who are able to transition to oral antimalarial therapy will initiate a 3-day course of artemisinin-combination oral therapy per national guidelines. The primary objective of the study is to determine the relationship between DHA exposures following IV artesunate dosing and markers of physiologic dysfunction associated with severe malaria in Ugandan children.

Detailed Description

This clinical study is a phase 4, single-site, open-label pharmacokinetic (PK) study of IV artesunate in up to 100 Ugandan children 6 months-14 years of age who are diagnosed with severe malaria according to standardized World Health Organization (WHO) criteria (any P. falciparum parasitemia and the presence of danger signs). Participants will receive the standard of care IV artesunate for initial treatment of severe malaria per WHO guidelines: children weighing <20 kg should receive 3.0 mg/kg/dose compared to children weighing =20 kg who should receive 2.4 mg/kg/dose, at times 0, 12, 24, 48 and 72 hours (WHO 2015). Parenteral treatment will be administered for a minimum of 24 hours (irrespective of the patient's ability to tolerate oral medication earlier), after which patients will be evaluated clinically and assessed for ability for oral intake of antimalarials. Children who are able to transition to oral antimalarial therapy will initiate a 3-day course of artemisinin-combination oral therapy per national guidelines. Biomarkers of physiologic dysfunction will be quantified at regular intervals, including serum lactate, serum glucose, total and direct bilirubin, bicarbonate levels, Blantyre Coma Score (BCS), creatinine and hemoglobin. These biomarkers will be considered both independently and together as a weighted score to relate to the PK of the active metabolite of IV artesunate, DHA and to efficacy markers that more accurately reflect clinical outcomes. We will also quantify P. falciparum parasitemia using standardized thick blood smear and relate this outcome to DHA dose and exposure for comparison with historical studies. Children 6 months to 14 years of age living in or near Tororo District, Uganda, who are diagnosed with severe malaria and who meet inclusion and exclusion criteria will be enrolled.

Conditions

Plasmodium Falciparum Infection

Keywords

Artesunate; Children; IV; P. falciparum; Severe Malaria; Uganda

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Participants will receive the standard of care with IV artesunate for treatment of severe malaria. Each 60-mg vial of artesunic acid will be dissolved in 1 mL of 5% sodium bicarbonate to form sodium artesunate and then mixed with 5 mL of 5% dextrose. This will be injected as a bolus into an indwelling IV cannula. Children weighing \<20 kg will receive IV artesunate at a dose of 3.0 mg/kg/dose compared to older children weighing \>/= 20kg who will receive 2.4 mg/kg/dose, at times 0, 12, 24. If unable to take oral medication, IV artesunate will continue at 48 and 72 hours. Children who recover and are able to transition to oral antimalarial therapy after a minimum of 24 hours, will initiate a 3-day course of oral artemisinin-combination therapy per national guidelines. N = 100

Group Type: EXPERIMENTAL

Artesunate

Intervention Type: DRUG

Artesunate is a succinic ester of artemether.

Interventions

Artesunate

Artesunate is a succinic ester of artemether.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Children ages 6 months-14 years at the time of severe malaria diagnosis, inclusive

2. Meet the case definition for severe malaria, per WHO standardized guidelines

3. Parent/guardian willing to provide informed consent

4. Assent for children between 8 and 14 years who are conscious and otherwise able to provide assent, inclusive

Exclusion Criteria

1. Receipt of > 24 hours of artemisinin therapy

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Makerere University-Infectious Diseases Institute

Kampala, , Uganda

Countries

United States; Uganda

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

19-0007

Identifier Type: -

Identifier Source: org_study_id

5UM1AI148689-03

Identifier Type: NIH

Identifier Source: secondary_id

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