Sulfadoxine-pyrimethamine Plus Dihydroartemisinin-piperaquine for Intermittent Preventive Treatment in Pregnancy

NCT05426434 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 2021-4107
• Study Type: interventional
• Target: 1,172
• Locations: 1 country
• Sites: 1

Brief Summary

This trial tests the hypothesis that intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) plus dihydroartemisinin-piperaquine (DP) significantly reduces the risk of malaria infection (primary outcome) and adverse birth outcomes (key secondary outcome) in an endemic area of Papua New Guinea (PNG), compared to IPTp with SP alone (the current standard of care). To test this hypothesis a double-blinded, placebo-controlled, phase-III, superiority trial will individually randomize 1,172 HIV-uninfected pregnant women enrolled from 12-26 gestational weeks in equal proportions to one of two IPTp arms: 1) SP given every for weeks, or 2) SP+DP given every 4 weeks. DP placebos will be used to ensure adequate blinding is achieved in the study and follow-up will end 28 days after giving birth.

Conditions

Malaria; Malaria in Pregnancy; Pregnancy Related

Outcome Measures

Primary Outcomes (1)

• Malaria infection in pregnancy

  'Malaria infection in pregnancy' is a composite outcome, defined as one or more episode of P. falciparum and/or P. vivax infection, detected by microscopy and/or qPCR in peripheral blood or placental blood, or P. falciparum and/or P. vivax infection, detected as active infection on placental histology. The surveillance period will run from two weeks after the first dose of the first monthly treatment up until and including delivery (numerator) in women who attend at least one scheduled or unscheduled visit during the surveillance period (denominator). Proportion of women with 'malaria infection in pregnancy'

  Starting two weeks after initial dose until and including delivery

Secondary Outcomes (30)

• Adverse pregnancy outcome

  Time of delivery up to 28 days postpartum

• Clinical malaria during pregnancy

  Starting two weeks after initial dose until and including delivery

• Parasitemia during pregnancy

  Starting two weeks after initial dose until and including delivery

• Composite placental malaria detected by microscopy, qPCR or by histology

  At time of delivery

• Placental malaria detected by microscopy

  At time of delivery

Study Arms (2)

SP + DP placebo every 4 weeks

ACTIVE COMPARATOR

Control arm

Drug: Sulfadoxine pyrimethamine (SP)

SP + DP given every 4 weeks

EXPERIMENTAL

Intervention arm

Drug: Dihydroartemisinin-Piperaquine (DP); Drug: Sulfadoxine pyrimethamine (SP)

Interventions

Dihydroartemisinin-Piperaquine (DP) DRUG

DP (D-Artepp) will be supplied by Fosun Pharma, China. DP will consist of three 40mg/320mg) tablets given once a day for three consecutive days

Also known as: D-Artepp

SP + DP given every 4 weeks

Sulfadoxine pyrimethamine (SP) DRUG

SP (G-COSPE) will be supplied by Fosun Pharma, China. SP will be given as a single dose consisting of three 500mg/25mg tablets.

Also known as: G-COSPE

SP + DP given every 4 weeks; SP + DP placebo every 4 weeks

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Pregnant women between 12-26 weeks' gestation
• years of age or older
• Viable singleton intrauterine pregnancy
• Permanent resident of the study area
• Willing to adhere to scheduled and unscheduled study visit procedures
• Willing to birth in a study clinic or hospital
• Able to provide written informed consent

You may not qualify if:

• Multiple pregnancy (i.e. twins/triplets)
• Known heart ailment or other chronic medical condition requiring frequent hospital care
• Active medical problem requiring inpatient evaluation at the time of screening
• Severe malformations or non-viable pregnancy if observed by ultrasound
• Antimalarial therapy in the prior two weeks
• Unable to provide written informed consent
• Known allergy or contraindication to any of the study drugs
• Early or active labour
• Known HIV-positive status

Sponsors & Collaborators

• Menzies School of Health Research: lead
• Papua New Guinea Institute of Medical Research: collaborator
• University of Melbourne: collaborator
• Curtin University: collaborator
• Liverpool School of Tropical Medicine: collaborator

Study Sites (1)

Papua New Guinea Institute of Medical Research

Madang, Madang Province, 511, Papua New Guinea

Location

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Holger Unger, PhD MBChB

  Menzies School of Health Research, Darwin, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo, or SP and DP) followed by one drug on days 2 and 3 (placebo or DP). One placebo that mimics the appearance of DP will be used. A randomization list will be computer generated by a member of the project who will not be directly involved in the conduct of the study. The randomization list will include consecutive treatment numbers with corresponding random treatment assignments. Randomized codes will correspond to the 2 treatment arms using permuted variable sized blocks.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blinded randomized controlled trial

Study Record Dates

• First Submitted: June 14, 2022
• First Posted: June 22, 2022
• Study Start: August 31, 2022
• Primary Completion: March 31, 2025
• Study Completion: December 1, 2025
• Last Updated: June 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)