Ignite Creation Date:
2025-12-25 @ 2:18 AM
Ignite Modification Date:
2025-12-26 @ 5:25 PM
Study NCT ID:
NCT05426434
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-06-06
First Post:
2022-06-14
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Sulfadoxine-pyrimethamine Plus Dihydroartemisinin-piperaquine for Intermittent Preventive Treatment in Pregnancy
Sponsor:
Menzies School of Health Research
Organization:
Study Overview
Official Title:
Intermittent Preventive Treatment in Pregnancy With Sulfadoxine-pyrimethamine Plus Dihydroartemisinin-piperaquine to Prevent Malaria Infection and Reduce Adverse Pregnancy Outcomes in Papua New Guinea - a Randomised Controlled Trial
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SAPOT
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.
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.
Detailed Description:
Plasmodium falciparum and P. vivax infections cause malaria, maternal anemia and interfere with the development of the fetus, thereby increasing the risks of adverse pregnancy outcomes such as miscarriage, stillbirth, premature birth, fetal growth restriction, low birth weight, and infant death. Infected pregnant women are frequently asymptomatic, and current point-of-care tests miss placental and low-density infections. Monthly intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is designed to clear asymptomatic infections and provide post-treatment prophylaxis. The World Health Organization recommends IPTp with SP and long-lasting insecticidal bed nets for the prevention of malaria in pregnancy in endemic areas of sub-Saharan Africa. However, the emergence and spread of high-grade parasite resistance to SP threatens to compromise this strategy. Dihydroartemisinin-piperaquine (DP) is a safe fixed-dose artemisinin-based combination therapy used for the management of uncomplicated P. falciparum and P. vivax malaria in pregnancy and has emerged as a potential candidate to replace SP for IPTp. In comparative trials conducted in high-transmission settings in sub-Saharan Africa IPTp with DP was safe and significantly reduced the risk of P. falciparum infection compared to IPTp with SP. IPTp with DP also reduced the risk of P. vivax parasitemia in Papua Indonesia when compared to a single screen and treat approach. However, DP's superior antimalarial efficacy in African studies did not translate to large reductions in adverse pregnancy outcomes in these trials. This suggests that SP, whilst failing as an antimalarial, may prevent adverse pregnancy events via potent non-malarial effects that are not inherent to DP. For example, SP may provide protection from pathogens other than malaria parasites that are directly or indirectly involved in the causation of adverse pregnancy outcomes.
Papua New Guinea (PNG) is characterized by moderate intensity co-transmission of P. falciparum and P. vivax and a high burden of adverse pregnancy outcomes. PNG is the only country outside of Africa that has a policy of IPTp with SP. However, P. vivax resistance to SP is now common, high-grade P. falciparum resistance to SP may be emerging, and DP could provide enhanced antimalarial protection. However, given the high burden of adverse pregnancy outcomes from malaria- and non-malaria related causes, simply replacing SP with DP for IPTp in PNG may not lead to a reduction in adverse birth outcomes. Instead, combining DP with SP for IPTp has the potential to substantially improve health outcomes by reducing the risk of malaria infection whilst harnessing the non-malaria-related benefits of SP.
A double-blinded randomized controlled clinical trial will (1) compare the risk of malaria infection among pregnant women randomized to receive monthly IPTp with SP vs. SP+DP; (2) compare the risk of adverse pregnancy outcomes among pregnant women randomized to receive monthly IPTp with SP vs. SP+DP; and (3) compare safety and tolerability of monthly IPTp with SP vs SP+DP. The findings of this trial may have important policy implications, and the evidence generated will inform practice for PNG and sub-Saharan Africa.
Papua New Guinea (PNG) is characterized by moderate intensity co-transmission of P. falciparum and P. vivax and a high burden of adverse pregnancy outcomes. PNG is the only country outside of Africa that has a policy of IPTp with SP. However, P. vivax resistance to SP is now common, high-grade P. falciparum resistance to SP may be emerging, and DP could provide enhanced antimalarial protection. However, given the high burden of adverse pregnancy outcomes from malaria- and non-malaria related causes, simply replacing SP with DP for IPTp in PNG may not lead to a reduction in adverse birth outcomes. Instead, combining DP with SP for IPTp has the potential to substantially improve health outcomes by reducing the risk of malaria infection whilst harnessing the non-malaria-related benefits of SP.
A double-blinded randomized controlled clinical trial will (1) compare the risk of malaria infection among pregnant women randomized to receive monthly IPTp with SP vs. SP+DP; (2) compare the risk of adverse pregnancy outcomes among pregnant women randomized to receive monthly IPTp with SP vs. SP+DP; and (3) compare safety and tolerability of monthly IPTp with SP vs SP+DP. The findings of this trial may have important policy implications, and the evidence generated will inform practice for PNG and sub-Saharan Africa.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: