Optimal Chemopreventive Regimens to Prevent Malaria and Improve Birth Outcomes in Uganda

NCT04336189 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: DPSP
• Study Type: interventional
• Target: 2,757
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria

Keywords

dihydroartemisinin-piperaquine; sulfadoxine-pyrimethamine; IPTp; reproductive tract infection; microbiome; drug resistance

Outcome Measures

Primary Outcomes (3)

• Risk of Having a Composite Adverse Birth Outcome

  Composite adverse birth outcome defined as the occurrence of any of the following: * Spontaneous abortion: Fetal loss at \< 28 weeks gestational age * Stillbirth: Infant born deceased at \> 28 weeks gestational age * Low Birth Weight (LBW): Live birth with birth weight \< 2500 gm * Preterm birth: Live birth at \< 37 weeks gestational age * Small-for-gestational age (SGA): Live birth with weight-for-gestational age \< 10th percentile of reference population * Neonatal death: Live birth with neonatal death within the first 28 days of life

  Time from first dose of study drugs up to 28 days postpartum, an average of 6 months

• Incidence of Serious Adverse Events (SAE) Per Time at Risk

  SAEs as defined by the July 2017 NIH DAIDS Toxicity Tables

  Time from first dose of study drugs up to 28 days postpartum, an average of 6 months

• Incidence of Any Grade 3 or 4 or Serious Adverse Events Per Time at Risk

  Grade 3 and 4 AEs or SAEs as defined by the July 2017 NIH DAIDS Toxicity Tables

  Time from first dose of study drugs up to 28 days postpartum, an average of 6 months

Secondary Outcomes (23)

• Number of Participants With Spontaneous Abortion

  Time of delivery

• Incidence of Anemia Adverse Event Per Time at Risk

  Day study drugs are first given until when study participants reach 28 days postpartum or early study termination, an average of 6 months

• Incidence of Grade 3-4 AEs Possibly Related to Study Drugs

  Day study drugs are first given until when study participants reach 28 days postpartum or early study termination, an average of 6 months

• Risk of Placental Malaria

  At the time of delivery

• Incidence of Malaria During Pregnancy

  Day study drugs first given until delivery, an average of 6 months

Study Arms (3)

SP + DP placebo every 4 weeks

ACTIVE COMPARATOR

Drug: Sulfadoxine-pyrimethamine (SP)

DP + SP placebo every 4 weeks

ACTIVE COMPARATOR

Drug: Dihydroartemisinin-piperaquine (DP)

SP + DP given every 4 weeks

ACTIVE COMPARATOR

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

Interventions

Sulfadoxine-pyrimethamine (SP) DRUG

SP (Kamsidar) will be supplied by Kampala Pharmaceutical Industries (KPI), Uganda. SP will be given as a single dose consisting of 3 full strength tablets.

Also known as: Kamsidar

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

Dihydroartemisinin-piperaquine (DP) DRUG

DP (Duo-Cotecxin) will be supplied by Holley-Cotec, Beijing, China. DP will consist of 3 full strength tablets given once a day for 3 consecutive days.

Also known as: Duo-Cotecxin

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

Eligibility Criteria

• Age: 16 Years+
• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Viable singleton pregnancy confirmed by ultrasound
• Estimated gestational age between 12-20 weeks
• Confirmed to be HIV- uninfected by rapid test
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Grant Dorsey, M.D, Ph.D.: lead
• National Institutes of Health (NIH): collaborator
• Infectious Diseases Research Collaboration, Uganda: collaborator

Study Sites (1)

Infectious Diseases Research Collaboration Clinic - Masafu Hospital

Masafu, Busia, Uganda

Location

Related Publications (1)

• Kakuru A, Kizza J, Aguti M, Adrama H, Ategeka J, Olwoch P, Nakalembe M, Nankabirwa JI, Opira B, Ozarslan N, Ranjit A, Dela Cruz E, Clark TD, Roh ME, Gaw SL, Jagannathan P, Rosenthal PJ, Kamya MR, Dorsey G. Dihydroartemisinin-piperaquine plus sulfadoxine-pyrimethamine versus either drug alone for intermittent preventive treatment of malaria in pregnancy: A double-blind, randomized, controlled phase 3 trial from Uganda. PLoS Med. 2025 Sep 18;22(9):e1004582. doi: 10.1371/journal.pmed.1004582. eCollection 2025 Sep.

  PMID: 40966190 DERIVED

MeSH Terms

Conditions

Malaria; Reproductive Tract Infections

Interventions

fanasil, pyrimethamine drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases

Results Point of Contact

• Title: Grant Dorsey
• Organization: UCSF

grant.dorsey@ucsf.edu

415-310-0525

Study Officials

• Grant Dorsey, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Phil Rosenthal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Moses Kamya, MBChB, MMed, PhD

  Makerere University; Infectious Diseases Research Collaboration

  PRINCIPAL INVESTIGATOR

• Abel Kakuru, MBChB, PhD

  Infectious Diseases Research Collaboration

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• 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 DP and placebo or SP and DP) followed by one drug on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. 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 3 treatment arms using permuted variable sized blocks of 6 and 9.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle Investigator

Model Details: Double blinded randomized controlled trial

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 7, 2020
• Study Start: December 28, 2020
• Primary Completion: July 28, 2024
• Study Completion: July 28, 2024
• Last Updated: November 6, 2025
• Results First Posted: November 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)