Clinical trial NCT05676645: Pharmacokinetics of Antimalarials in Breastfeeding Ugandan Mother-infant Pairs
Official title: Pharmacokinetics of Drugs Used to Treat Uncomplicated Malaria in Breastfeeding Mother-infant Pairs: An Observational Pharmacokinetic Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Malaria,Falciparum
Lead sponsor: University of Liverpool
Sponsor class: OTHER
Collaborators: name: Makerere University
name: Malawi-Liverpool-Wellcome Clinical Research Programme
First posted: 2023-01-09
Enrollment: 30
Sex: FEMALE
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Ugandan breastfeeding women requiring treatment for uncomplicated malaria

Brief summary: Lactating women requiring treatment for uncomplicated malaria will be identified and invited for sampling. The decision to treat them with first-line treatment will have been made by the clinician, not by a member of the study team. The study team will not make any adjustments to the prescribed treatment. Artemether-lumefantrine comprises six doses of medication, with the initial two doses given 8 hours apart on Day 1, and dosing 12-hourly on Day 2 and Day 3. Intensive pharmacokinetic sampling will be undertaken after Dose 5, as indicated in the schema under Section 5: plasma and breastmilk samples will be obtained pre-dose and at 2, 4, 6, 8 hours after dose. In addition, sparse sampling will be undertaken on either of these occasions; at pre-dose and between 1 to 6 hours after the first dose; a trough (pre-dose) sample after the Dose 3 or Dose 4 and lastly at 5, 7, and up to 14-days after the first dose. A heelprick sample will also be obtained from the breastfed infants at maternal trough (prior to maternal dose) and at a random timepoint (once per infant) over the 8-hour pharmacokinetic sampling visit to characterize concentrations of these drugs over an 8-hour dosing interval. In addition, a single heelprick sample will be obtained from the infant whenever the mother returns after treatment for the late sampling time points (5, 7, and 14 days post the first dose). Due to the long half-life of lumefantrine of approximately 6 days plasma sampling will be performed up to day 14 to characterise the terminal elimination of the drug. Concentrations of total plasma and breastmilk lumefantrine and desbutyl-lumefantrine will be determined.

Detailed description: The endpoints of this study relate to the amount of antimalarial drug present in maternal blood, breastmilk and infant blood. The study is not powered for antimalarial efficacy, and therefore formal assessment of parasitological clearance is not required. The participants will be followed up until 30-40 days after completion of antimalarial therapy, and if recurrent symptoms occur, management will be as clinically indicated. Details regarding further clinical investigations and management required by either mother or infant during the follow-up period will be recorded on the CRF.

Eligibility criteria: Inclusion Criteria:

1. A personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
2. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Woman is aged 18 years or older, and mothers between the age of 14-17, who are considered emancipated minors.
4. Receiving treatment for uncomplicated malaria
5. Breastfeeding at enrolment

Exclusion Criteria:

1. Severe maternal or infant illness which in the opinion of the patient's clinician would interfere with her participation in the study
2. Breastfed infant is aged over 12 months
3. Partner objection to participate in the study
4. Maternal objection to infant participation

Primary outcomes:
measure: AUC0-24 of lumefantrine in maternal plasma and breastmilk
timeFrame: 0-24 hours after dose
measure: AUC0-24 of lumefantrine breastmilk
timeFrame: 0-24 hours after dose
measure: Milk to plasma ratio of lumefantrine
timeFrame: 0-24 hours after dose
Secondary outcomes:
measure: AUC desbutyl-lumefantrine plasma
timeFrame: 0-24 hours after dose
measure: AUC desbutyl-lumefantrine breastmilk
timeFrame: 0-24 hours after dose
measure: Milk to plasma ratio of desbutyl-lumefantrine
timeFrame: 0-24 hours after dose
measure: Infant concentration lumefantrine
timeFrame: 0-8 hours after maternal dose
measure: Infant concentration desbutyl-lumefantrine
timeFrame: 0-8 hours after maternal dose
measure: Infant development
timeFrame: 0-1 year old
measure: Depression and anxiety in mothers
timeFrame: 0-1 year postpartum
measure: Depression and anxiety in mothers
timeFrame: 0-1 year postpartum
measure: Maternal beliefs about medicines
timeFrame: 0-1 year postpartum
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Infectious Diseases Institute
Study officials:
References: