A study investigating the efficacy of artemisinin combination therapy to prevent postpartum malaria and as a treatment for uncomplicated malaria in young infants.

Status

Recruiting

Phases

Phase 4

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12620000942954

Enrollment

172

Registered

2020-09-21

Start date

2018-08-21

Completion date

2020-09-30

Last updated

2020-09-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Women in tropical countries are likely to be at significant risk of postpartum malaria. This could have implications for maternal health including anaemia. Malaria in infants in the first 6 months of life is under-recognised, can remain untreated, and have more serious consequences than previously thought. There is a need for studies that i) evaluate the efficacy of a maternal treatment course of artemisinin combination therapy (ACT) at delivery, ii) assess whether transfer of the component drugs into breast milk can lead to protection of the infant against malaria or, by contrast, toxicity especially if the infant is treated for malaria with ACT, and iii) characterise the pharmacokinetics and preliminary efficacy of ACT in infants with malaria so that appropriate treatment regimens can be developed. The proposed studies, to be carried out in north coastal Papua New Guinea (PNG), address these needs through i) a randomised trial of no treatment (current national policy) vs ACT in pregnant PNG women presenting in labour with a primary endpoint of any slide-positive malaria detected either from symptomatic presentation or on prospective monthly screening within 6 months of delivery, ii) a study of the pharmacokinetics of ACT component drugs in breast milk and in small volume blood samples in the suckling infants, and iii) a preliminary pharmacokinetic and efficacy evaluation of ACT in infants found to have malaria in the first 6 months of life. The data should prove valuable in informing prevention and treatment of malaria in mother and child in the postpartum period in PNG and other epidemiologically similar countries.

Interventions

Efficacy of ACT in preventing postpartum malaria (Main trial) Recruited participants will be recruited 1:1 to no-treatment and intervention groups. Those women randomised to the no-treatment group will received standard labour and postnatal care, with no interventional drugs administered. For women allocated to an intervention group, a further 1:1 randomisation to treatment Arm 1 (artemether-lumefantrine) and Arm 2 (dihydroartemisinin-piperaquine) will occur. Arm 1: Artemether-lumefantrine: Oral tablet administration as 1.7 mg/kg artemether and 10 mg/kg lumefantrine given twice-daily for 3 days with milk/food. Arm 2: Dihydroartemisinin-piperaquine: Oral tablet administration as 7 mg/kg dihydroartemisinin and 58 mg/kg piperaquine phosphate (equivalent to 33 mg/kg piperaquine base for a 50 kg woman) given once daily for 3 days with water. Allocated treatment will be administered within 24 hours of delivery, after lactation had been established and the infant had fed on first colostrum. All oral doses will be administered to the nearest full tablet with all morning doses directly observed by research staff, and evening artemether-lumefantrine doses taken at home if the mother is to be discharged. Women remaining in the labor ward over night will have their evening doses given under direct observation. Women vomiting within 30 minutes of dosing will be re-treated. Pharmacokinetics of ACT drugs in breast milk study (Sub-study 1) A randomly-selected subset of 40 of the 90 ACT-treated women enrolled in the Main trial (20 in each Arm) will be co-enrolled in Sub-study 1. Each participant will be exposed to the intervention as described above. Each participant will provide a 3-5mL fore- and hind-milk samples will be taken at 0.5-2 hours, 4-6 hours, 6-8 hours, 10-12 hours and on Days 1, 2, 3, 4, 7, 14 and 28 after drug administration Infant pharmacokinetic and preliminary efficacy study (Sub-study 2) Those of the 90 infants of mothers randomised to the no-treatment arm of the study who are found to have malaria at any time during the 6 months follow-up period will be randomised 1:1 by computer-generated schedule to: i) Artemether-lumefantrine: Oral tablet suspension administered as 2.0 mg/kg artemether and 12 mg/kg lumefantrine given twice-daily for 3 days given with breast milk, or ii) Dihydroartemisinin-piperaquine: Oral tablet suspension administered as 7 mg/kg dihydroartemisinin and 58 mg/kg piperaquine phosphate given once daily for 3 days with water or coconut milk (which is low in fat), as per manufacturer's recommendation. Those of the 90 infants of mothers randomised to the treatment arms of the study who are found to have malaria at any time during the 6 months follow-up period will be given artemether-lumefantrine initially, but subsequent pharmacokinetic analyses from samples taken in the breast milk sub-study and from the ACT-treated infants of the untreated mothers may indicate that it is safe for full randomisation to artemether-lumefantrine or dihydroartemisinin-piperaquine. Doses will be to the nearest quarter-tablet. Infants vomiting with 30 minutes of drug treatment will re-treated.

Study design

Allocation

Randomised controlled trial

Intervention model

Parallel

Primary purpose

Prevention

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Healthy volunteers

Inclusion criteria

Postpartum study (Main trial) i) >=18 years of age ii) Peripheral blood slide negative for malaria at delivery (slide positive women will receive conventional artemether-lumefantrine treatment and are not eligible for recruitment). ii) They have not received a study intervention in the previous 4 weeks. iii) They have not required medical/surgical intervention for complications during delivery, other than an episiotomy and broad spectrum antibiotic treatment. iv) They have no significant co-morbidity v) They can attend follow-up assessments over the full 6 months Infant study (Sub-study 2) i) infant born to Main trial study mother within the last 6 months. ii) positive blood slide or polymerase chain reaction positive for malaria during the 6 months' follow-up

Exclusion criteria

i) < 18 years of age ii) Husband/ father do not grant informed consent (as per Papua New Guinean custom) iii) Participant has a positive malaria blood slide or rapid diagnostic test at time of delivery. iv) Participant has a pre-term delivery v) Neonate demonstrating signs of illness or low APGAR score at delivery vi)Participant has received treatment with a study intervention in the past 4 weeks. vii) Participant has signs of a significant concomitant disease including malnutrition, tuberculosis, and pneumonia. viii) Surgical intervention was required during delivery. vi) Participant residence is outside health centre catchment area.

Outcome results