Postpartum WomenPhase 4PBCNCT06191458
Postpartum Primaquine in Breast Milk
A Phase 4 study testing Primaquine in people with Postpartum Women, run by University of Oxford at 1 site in Thailand.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postpartum Women
- What is being tested?
- Primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteThailand
- Study dates
- 9 Jul 2024to 23 Feb 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Shoklo Malaria Research Unit (SMRU)
Mae Ramat, Changwat Tak, 63140
About this study
Official title: Neonatal Exposure to Primaquine Through Breast Milk During Treatment in Postpartum Women
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.
Read more
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.
Read the detailed description
This is a prospective open-label, single site, dense pharmacokinetic study of primaquine (0.5 mg/kg daily for 14 days) taken by postpartum lactating women.
The study will take place the Shoklo Malaria Research Unit (SMRU), Mahidol Oxford Tropical Medicine Research Unit, Tak Province, Thailand. Pregnant women who access care at SMRU antenatal care will be invited to participate after delivery with their breastfed children. Recruitment will prioritize women with a history of P. vivax infection without radical cure, but will also accept healthy volunteers. All 12 lactating women and their breastfed neonates 48 hours - 5 days old will be G6PD phenotypically normal, confirmed by spectrophotometry.
Following informed consent, women attending SMRU antenatal care will be pre-screened during pregnancy for potential enrolment postpartum. Full screening must be repeated postpartum before enrolment.
Similar to the mothers, neonates will be pre-screened for eligibility using biosensor and Hb/Hct. Birth history will be reviewed to determine the absence of severe neonatal disease (neonatal sepsis, severe jaundice, significant birth asphyxia etc).
Mothers and neonates will be closely monitored for safety throughout the 28 day follow up period including regular assessments of adverse events, Hb, Hct and MetHb levels. If a neonate develops jaundice, treatment will follow the clinical guidelines of the site. The study sampling will continue as long as the baby is responding normally to phototherapy and inclusion in the study is not thought to interfere with clinical care. If methemoglobinemia is detected, it will be managed according to SMRU clinical protocol. Medication will be stopped if the participant is in the primaquine arm and a severe drug related AE occurs.
Pharmacokinetic (PK)sampling plan:
- Mothers: Dense PK venous blood and breast milk sampling will be performed during day 1 and 14; two blood samples and one breast milk sample will collected at a single timepoint on days 3, 5 and 8.
- Neonate: One capillary blood sample will be collected on the same days as maternal sampling.
PK drug measurements of primaquine, and carboxyprimaquine will be performed. Drug concentrations will be quantified by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using a validated assay according to regulatory guidelines.
This study is funded by Thrasher Research Fund, EW "Al" Thrasher award.
- Conditions
- Postpartum Women
- Being tested
- Primaquine
- Keywords
- Postpartum women, Primaquine, Pharmacokinetics, Healthy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrimaquineDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the time-concentration curve in milk
Area under the time-concentration curve (AUC) for primaquine in colostrum and transitional milk
Measured: 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.
Measured: 14 days
Secondary outcomes (7)
Area under the time-concentration curve in plasma
Area under the time-concentration curve (AUC) of primaquine for mother and neonate (if measurable concentrations found in neonatal plasma).
Measured: 14 days
Time to maximum concentration
Time to maximum concentration (Tmax) of primaquine for mother and neonate (if measurable concentrations found in neonatal plasma).
Measured: 14 days
Peak plasma concentration
Peak plasma or maximum concentration reached (Cmax) of primaquine for mother and neonate (if measurable concentrations found in neonatal plasma).
Measured: 14 days
Haematologic changes
Changes in haemoglobin (Hb), haematocrit (Hct) and methemoglobin (MetHb) in mothers and neonates over the period of drug exposure.
Measured: 14 days
Number of adverse events
Number of adverse events (AEs) in mothers and neonates during the period of drug exposure.
Measured: 14 days
Severity of adverse events
Severity of adverse events (AEs) in mothers and neonates during the period of drug exposure according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Measured: 14 days
Type of adverse events
Type of adverse events (AEs) in mothers and neonates during the period of drug exposure.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2024
- Study start9 Jul 2024
- Primary completion23 Feb 2025
- Study completion23 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postpartum WomenStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol Oxford Tropical Medicine Research Unit
- Responsible party
- Sponsor
- Investigators
- Rose McGready, Ph.D, Principal investigator, Shoklo Malaria Research Unit (SMRU)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06191458
- Sponsor's protocol ID
- MAL23004
- Acronym
- PBC
- Status last verified
- Aug 2024
- First submitted
- 20 Dec 2023
- Last updated
- 10 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data will be published in the open access medical literature with the identity of the participants protected. Criteria for authorship will follow international guidelines. Following completion of the study, the database will belong to the PI and key co-investigators. The deidentified database, including individual participant data, may be made freely available to other researchers via the Oxford University Research Archive. The results of the study will be shared with the local community.
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neonatal Exposure to Primaquine Through Breast Milk During Treatment in Postpartum Women
- ClinicalTrials.gov ID
- NCT06191458
- Acronym / sponsor ID
- PBC / MAL23004
- Conditions
- Postpartum Women
- Keywords
- Postpartum women, Primaquine, Pharmacokinetics, Healthy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Mahidol Oxford Tropical Medicine Research Unit
- Study start
- 9 Jul 2024 (actual)
- Primary completion
- 23 Feb 2025 (actual)
- Study completion
- 23 Feb 2025 (actual)
- First posted
- 5 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective open-label, single site, dense pharmacokinetic study of primaquine (0.5 mg/kg daily for 14 days) taken by postpartum lactating women.
The study will take place the Shoklo Malaria Research Unit (SMRU), Mahidol Oxford Tropical Medicine Research Unit, Tak Province, Thailand. Pregnant women who access care at SMRU antenatal care will be invited to participate after delivery with their breastfed children. Recruitment will prioritize women with a history of P. vivax infection without radical cure, but will also accept healthy volunteers. All 12 lactating women and their breastfed neonates 48 hours - 5 days old will be G6PD phenotypically normal, confirmed by spectrophotometry.
Following informed consent, women attending SMRU antenatal care will be pre-screened during pregnancy for potential enrolment postpartum. Full screening must be repeated postpartum before enrolment.
Similar to the mothers, neonates will be pre-screened for eligibility using biosensor and Hb/Hct. Birth history will be reviewed to determine the absence of severe neonatal disease (neonatal sepsis, severe jaundice, significant birth asphyxia etc).
Mothers and neonates will be closely monitored for safety throughout the 28 day follow up period including regular assessments of adverse events, Hb, Hct and MetHb levels. If a neonate develops jaundice, treatment will follow the clinical guidelines of the site. The study sampling will continue as long as the baby is responding normally to phototherapy and inclusion in the study is not thought to interfere with clinical care. If methemoglobinemia is detected, it will be managed according to SMRU clinical protocol. Medication will be stopped if the participant is in the primaquine arm and a severe drug related AE occurs.
Pharmacokinetic (PK)sampling plan:
- Mothers: Dense PK venous blood and breast milk sampling will be performed during day 1 and 14; two blood samples and one breast milk sample will collected at a single timepoint on days 3, 5 and 8.
- Neonate: One capillary blood sample will be collected on the same days as maternal sampling.
PK drug measurements of primaquine, and carboxyprimaquine will be performed. Drug concentrations will be quantified by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using a validated assay according to regulatory guidelines.
This study is funded by Thrasher Research Fund, EW "Al" Thrasher award.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Primaquine | Experimental | Drug: PrimaquineTwelve 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrimaquinePrimaquine 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). | Drug | Primaquine |
Primary outcome
Area under the time-concentration curve in milk
Time frame: 14 days
Area under the time-concentration curve (AUC) for primaquine in colostrum and transitional milk
Relative infant dose
Time frame: 14 days
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.
7 secondary outcomes
Area under the time-concentration curve in plasma
Time frame: 14 days
Time to maximum concentration
Time frame: 14 days
Peak plasma concentration
Time frame: 14 days
Haematologic changes
Time frame: 14 days
Number of adverse events
Time frame: 14 days
Severity of adverse events
Time frame: 14 days
Type of adverse events
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2025.
- Individual participant dataSharing planned: Yes. All data will be published in the open access medical literature with the identity of the participants protected. Criteria for authorship will follow international guidelines. Following completion of the study, the database will belong to the PI and key co-investigators. The deidentified database, including individual participant data, may be made freely available to other researchers via the Oxford University Research Archive. The results of the study will be shared with the local community.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rose McGready, Ph.D principal investigator
Shoklo Malaria Research Unit (SMRU)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Primaquine in people with Postpartum Women, run by University of Oxford at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the time-concentration curve in milk (time frame: 14 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2025.