Phase 3
N=2,757
Optimal Chemopreventive Regimens to Prevent Malaria and Improve Birth Outcomes in Uganda
Malaria
Bottom Line
View on ClinicalTrials.gov: NCT04336189 ↗Enrolled (actual)
2,757
Serious AEs
2.9%
Results posted
Nov 2025
Primary outcome: Primary: Risk of Having a Composite Adverse Birth Outcome — 222; 261; 255 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sulfadoxine-pyrimethamine (SP) (Drug); Dihydroartemisinin-piperaquine (DP) (Drug)
- Age
- Pediatric, Adult, Older Adult · 16+ yrs
- Sex
- Female
- Sponsor
- Grant Dorsey, M.D, Ph.D.
- Primary completion
- Jul 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Risk of Having a Composite Adverse Birth Outcome |
222; 261; 255 | — |
| PRIMARY Incidence of Serious Adverse Events (SAE) Per Time at Risk |
0.06; 0.06; 0.06 | — |
| PRIMARY Incidence of Any Grade 3 or 4 or Serious Adverse Events Per Time at Risk |
0.23; 0.19; 0.21 | — |
| SECONDARY Number of Participants With Spontaneous Abortion |
12; 16; 13 | — |
| SECONDARY Incidence of Anemia Adverse Event Per Time at Risk |
53; 28; 44 | — |
| SECONDARY Incidence of Grade 3-4 AEs Possibly Related to Study Drugs |
50; 29; 41 | — |
| SECONDARY Risk of Placental Malaria |
472; 324; 393 | — |
| SECONDARY Incidence of Malaria During Pregnancy |
1.15; 0.02; 0.04 | — |
| SECONDARY Microscopic Parasitemia During Pregnancy |
771; 25; 60 | — |
| SECONDARY Prevalence of Anemia During Pregnancy |
965; 827; 880 | — |
| SECONDARY Stillbirth |
15; 16; 7 | — |
| SECONDARY Low Birth Rate |
47; 59; 71 | — |
| SECONDARY Preterm Delivery |
48; 25; 44 | — |
| SECONDARY Small-for-gestational Age |
152; 206; 194 | — |
| SECONDARY Neonatal Death |
4; 5; 12 | — |
| SECONDARY Microscopic or Sub-microscopic Parasitemia During Pregnancy |
2099; 551; 60 | — |
| SECONDARY Prevalence of Severe Anemia During Pregnancy |
29; 9; 12 | — |
| SECONDARY Incidence of Stillbirth Adverse Event Per Time at Risk |
15; 16; 7 | — |
| SECONDARY Incidence of Congenital Anomaly Adverse Event Per Time at Risk |
4; 13; 10 | — |
| SECONDARY Incidence of Neutropenia Adverse Event Per Time at Risk |
5; 10; 7 | — |
| SECONDARY Incidence of Proteinuria Adverse Event Per Time at Risk |
3; 4; 8 | — |
| SECONDARY Incidence of Thrombocytopenia Adverse Event Per Time at Risk |
7; 1; 2 | — |
| SECONDARY Incidence of Postpartum Hemorrhage Adverse Event Per Time at Risk |
2; 3; 2 | — |
| SECONDARY Incidence of Pre-eclampsia Adverse Event Per Time at Risk |
3; 0; 2 | — |
| SECONDARY Incidence of Preterm Birth <28 Gestational Age Adverse Event Per Time at Risk |
0; 0; 3 | — |
| SECONDARY Incidence of Elevated Temperature Adverse Event Per Time at Risk |
2; 1; 0 | — |
Summary
This trial tests the hypothesis that intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) + dihydroartemisin-piperaquine (DP) will significantly reduce the risk of adverse birth outcomes compared to IPTp with SP alone or DP alone. This double-blinded randomized controlled phase III trial of 2757 HIV uninfected pregnant women enrolled at 12-20 weeks gestation will be randomized in equal proportions to one of three IPTp treatment arms: 1) SP given every 4 weeks, or 2) DP given every 4 weeks, or 3) SP+DP given every 4 weeks. SP or DP placebos will be used to ensure adequate blinding is achieved in the study and follow-up will end 28 days after giving birth.
Eligibility Criteria
Inclusion Criteria
- Viable singleton pregnancy confirmed by ultrasound
- Estimated gestational age between 12-20 weeks
- Confirmed to be HIV- uninfected by rapid test
- 16 years of age or older
- Residency within Busia District of Uganda
- Provision of informed consent
- Agreement to come to the study clinic for any febrile episode or other illness and avoid medications given outside the study protocol
- Willing to deliver in the hospital
Exclusion Criteria
- History of serious adverse event to SP or DP
- Active medical problem requiring inpatient evaluation at the time of screening
- Intention of moving outside of Busia District Uganda
- Chronic medical condition requiring frequent medical attention
- Prior chemopreventive therapy or any other antimalarial therapy during this pregnancy
- Early or active labor (documented by cervical change with uterine contractions)
- Multiple pregnancies (i.e. twins/triplets)
Data sourced from ClinicalTrials.gov (NCT04336189). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.