Pharmacokinetic Study of IV Artesunate to Treat Children With Severe Malaria

NCT05750459 | Completed Phase 4 FDA Drug

• 2 other identifiers: 19-00075UM1AI148689-03
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Plasmodium Falciparum Infection

Keywords

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

Outcome Measures

Primary Outcomes (12)

• Change from baseline bicarbonate levels

  Day 1 through Day 183

• Change from baseline creatinine.

  Day 1 through Day 183

• Change from baseline diastolic blood pressure

  Day 1 through Day 183

• Change from baseline in Blantyre Coma Score (BCS).

  Day 1 through Day 183

• Change from baseline in concentration of Dihydroartemisinin (DHA)

  Pharmacokinetic parameters that will be derived from the concentration of Dihydroartemisinin (DHA) include maximum concentration (C max), area under the curve over hours 0-12 (AUC 0-12) and half-life (t 1/2) and time to C max (T max).

  Day 1

• Change from baseline in direct bilirubin

  Day 1 through Day 183

• Change from baseline in hemoglobin

  Day 1 through Day 183

• Change from baseline in serum glucose

  Day 1 through Day 183

• Change from baseline in temperature.

  Day 1 through Day 183

• Change from baseline in total bilirubin

  Day 1 through Day 183

• Change from baseline in venous serum lactate.

  Day 1 through Day 183

• Change from baseline systolic blood pressure

  Day 1 through Day 183

Secondary Outcomes (2)

• Parasite (P. falciparum) density in thick blood smear.

  Day 1 through Day 5 minimum

• Time to hospital discharge.

  Day 1 through 183

Study Arms (1)

Arm 1

EXPERIMENTAL

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

Drug: Artesunate

Interventions

Artesunate DRUG

Artesunate is a succinic ester of artemether.

Arm 1

Eligibility Criteria

• Age: 6 Months - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children ages 6 months-14 years at the time of severe malaria diagnosis, inclusive
• Meet the case definition for severe malaria, per WHO standardized guidelines
• Parent/guardian willing to provide informed consent
• Assent for children between 8 and 14 years who are conscious and otherwise able to provide assent, inclusive

You may not qualify if:

• \. Receipt of \> 24 hours of artemisinin therapy

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Makerere University-Infectious Diseases Institute

Kampala, Uganda

Location

MeSH Terms

Conditions

Malaria

Interventions

Artesunate

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2023
• First Posted: March 1, 2023
• Study Start: November 29, 2023
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: December 22, 2025

Record last verified: 2025-10-09

Locations

UG (1)