Postpartum Primaquine in Breast Milk

NCT06191458 | Completed Phase 4

• 1 other identifier: MAL23004
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Plasmodium vivax and ovale infections both follow chronically relapsing courses, leading to cumulative morbidity and mortality. P. vivax is the second most common malaria worldwide, with an estimated 13.8 million cases annually, and there is increasing concern about severe illness and death in vulnerable populations. Radical cure of P.vivax and P.ovale with 8-aminoquinolines is necessary to prevent relapse. The most widely 8-aminoquinoline is primaquine (7-14 day course), which has been used for almost 75 years. Its widespread use is hampered by the potentially severe haemolysis primaquine may trigger in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common red blood cell enzyme deficiency in the world. Safe administration of primaquine requires at least 30% of normal G6PD activity to avoid significant hemolysis. Screening for malaria is routine in pregnancy, leading to improved detection of P. vivax infections, but primaquine and is contraindicated in pregnancy. As a result, relapses of P. vivax are common in postpartum and lactating women. Normal G6PD activity levels in infants less than 6 months old have only recently been described and have only been established along the Thailand-Myanmar border. Most low-resource settings are therefore unable to determine infant G6PD status. Uncertainty about infant G6PD status means that breastfeeding women are rarely offered radical cure because of theoretical concerns about drug exposure through breast milk triggering haemolysis in breastfed infants and children with G6PD deficiency. Though neonates generally have higher G6PD activity than adults, increased haemolysis for a neonate could theoretically contribute to neonatal jaundice and anaemia. Understanding drug exposure to a breastfeeding neonate is operationally important, as interventions that can be safely offered before women leave the hospital postpartum have higher uptake. Current World Health Organization guidelines advise against prescribing primaquine to lactating women if they are breastfeeding infants less than 6 months old, or breastfeeding infants with G6PD deficiency or unknown G6PD status.

Conditions

Postpartum Women

Keywords

Postpartum women; Primaquine; Pharmacokinetics; Healthy

Outcome Measures

Primary Outcomes (2)

• Area under the time-concentration curve in milk

  Area under the time-concentration curve (AUC) for primaquine in colostrum and transitional milk

  14 days

• Relative infant dose

  Relative infant dose (RID) is a measure of the weight-adjusted dose of the study medication that the infant is exposed to via the breast milk. It is the most clinically relevant measure of the safety for a breastfed child of maternal medication use. RID for primaquine will be calculated using AUCs for drug in maternal plasma and colostrum, and transitional milk.

  14 days

Secondary Outcomes (7)

• Area under the time-concentration curve in plasma

  14 days

• Time to maximum concentration

  14 days

• Peak plasma concentration

  14 days

• Haematologic changes

  14 days

• Number of adverse events

  14 days

Study Arms (1)

Primaquine

EXPERIMENTAL

Twelve healthy postpartum women who are breast feeding healthy neonates 48 hours - 5 days old will receive primaquine 0.5 mg/kg once daily for 14 days.

Drug: Primaquine

Interventions

Primaquine DRUG

Primaquine 0.5 mg/kg (Government Pharmaceutical Organization, Thailand) will be given once daily with food for 14 days. This is the dose recommended by the World Health Organization for radical cure of P. vivax in tropical regions. Doses will be directly supervised (DOT).

Primaquine

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Healthy lactating woman aged more than or equal to 18 years old
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Lactating woman \>= 18 years old
• Planning to breastfeed for the duration of the study
• Breastfeeding one infant 48 hours - 5 days old
• Willingness and ability to comply with the study protocol for the duration of the study
• Can understand information about the study and provide consent
• Healthy neonate 48 hours - 5 days old

You may not qualify if:

• Known hypersensitivity to Primaquine (PMQ), defined as history of erythroderma/other severe cutaneous reaction, angioedema or anaphylaxis
• Known Glucose-6-phosphate-dehydrogenase (G6PD) deficiency in mother defined as G6PD activity \<70% of normal male population median by spectrophotometry
• Presence of any condition which in the judgement of the investigator would place the participant at undue risk or interfere with the results of the study
• Screening Hct \<33% by complete blood count (CBC)
• Known history of severe jaundice in a previous child
• Blood transfusion within the 3 months before screening
• Known Glucose-6-phosphate-dehydrogenase (G6PD) deficiency in neonate defined as G6PD activity \<70% of normal male population median by spectrophotometry
• Presence of any condition which in the judgement of the investigator would place the participant at undue risk or interfere with the results of the study
• Screening Hct \<40% by CBC
• Estimated gestational age at birth \< 38 weeks
• Evidence of birth asphyxia (5 min Apgar score \<7)
• Moderate or severe jaundice as defined as total serum bilirubin above treatment line on day 1 (before maternal dose)

Sponsors & Collaborators

• University of Oxford: lead
• Mahidol Oxford Tropical Medicine Research Unit: collaborator

Study Sites (1)

Shoklo Malaria Research Unit (SMRU)

Mae Ramat, Changwat Tak, 63140, Thailand

Location

MeSH Terms

Interventions

Primaquine

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Rose McGready, Ph.D

  Shoklo Malaria Research Unit (SMRU)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 5, 2024
• Study Start: July 9, 2024
• Primary Completion: February 23, 2025
• Study Completion: February 23, 2025
• Last Updated: June 10, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After completion of trial activities. PI will upload results within 12 months of the end of the trial declaration.
• Access Criteria: SMRU and MORU Data Sharing Policies

Locations

TH (1)