Reducing the Burden of Malaria in HIV-uninfected Pregnant Women and Infants
PROMOTE-BC1
2 other identifiers
interventional
300
1 country
1
Brief Summary
This will be a double-blinded randomized controlled phase III trial of 300 HIV uninfected pregnant women and the children born to them. The study interventions will be divided into two phases. In the first phase, HIV uninfected women at 12-20 weeks gestation will be randomized in equal proportions to one of three intermittent preventive therapy in pregnancy (IPTp) treatment arms: 1) 3 doses of sulfadoxine-pyrimethamine (SP), 2) 3 doses of dihydroartemisinin-piperaquine (DP), or 3) monthly DP. All three interventions arms will have either SP or DP placebo to ensure adequate blinding is achieved. Follow-up for the pregnant women will end approximately 6 weeks after giving birth. In the second phase of the study, all children born to mothers enrolled in the study will be followed from birth until they reach 36 months of age. Children born to mothers randomized to receive 3 doses of SP during pregnancy will receive DP every 3 months between 2-24 months of age. Children born to mothers randomized to receive 3 doses of DP or monthly DP during pregnancy will receive either DP every 3 months or monthly DP between 2-24 months of age. To ensure adequate blinding, children who will receive DP every 3 months will be given DP placebo during the months they will not be taking DP. Children will then be followed an additional year between 24-36 months of age following the interventions. We will test the hypothesis that IPT with DP will significantly reduce the burden of malaria in pregnancy and infancy and improve the development of naturally acquired antimalarial immunity.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2014
Typical duration for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 5, 2014
CompletedFirst Posted
Study publicly available on registry
June 13, 2014
CompletedStudy Start
First participant enrolled
June 23, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 14, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
May 14, 2018
CompletedResults Posted
Study results publicly available
November 14, 2018
CompletedDecember 18, 2024
December 1, 2024
3.9 years
June 5, 2014
August 17, 2018
December 16, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Prevalence of Placental Malaria
Prevalence of placental malaria based on placental histopathology dichotomized into any evidence of placental infection (parasites or pigment) vs. no evidence and by histopathology as a categorical variable based on Rogerson et al criteria.
Delivery
Incidence of Malaria in Pregnant Women
Incidence of malaria, defined as the number of incident episodes per time at risk. Incident cases will include all treatments for malaria not proceeded by another treatment in the previous 14 days.
Time at risk will begin after first dose of study drug and will end when study participants deliver or early study termination
Incidence of Malaria in Infants
Incident cases will include all treatments for malaria not proceeded by another treatment in the previous 14 days. The study investigators will test the hypotheses that A) infants born to mothers randomized to receive IPTp with 3 dose DP or monthly DP will have a lower incidence of malaria during the first 24 months of life compared to infants born to mothers who were randomized to receive IPTp with 3 doses of SP, and, B) infants randomized to receive monthly DP between 2-24 months of age will have a lower incidence of malaria between 24-36 months of age after the intervention is stopped compared to infants randomized q 3 monthly DP between 2-24 months of age.
Time at risk will begin at birth and will end when study participants reaches 24 months of age or early study termination (if prior to 24 months of age)
Incidence of Malaria in Infants
Incident cases will include all treatments for malaria not proceeded by another treatment in the previous 14 days. The study investigators will test the hypotheses that A) infants born to mothers randomized to receive IPTp with 3 dose DP or monthly DP will have a lower incidence of malaria during the first 24 months of life compared to infants born to mothers who were randomized to receive IPTp with 3 doses of SP, and, B) infants randomized to receive monthly DP between 2-24 months of age will have a lower incidence of malaria between 24-36 months of age after the intervention is stopped compared to infants randomized q 3 monthly DP between 2-24 months of age.
Time at risk will begin at 24 months of age and will end when study participants reaches 36 months of age or termination
Secondary Outcomes (10)
Number of Participants With Blood Samples Positive for Parasites by Microscopy or LAMP
Delivery
Number of Participants With Maternal Blood Samples Positive for Parasites by Microscopy and LAMP at Delivery
At delivery
Number of Participants With One or More Birth Outcomes: Congenital Malformations, Spontaneous Abortion, LBW (<2500g), Still Birth, Pre-term Delivery
Delivery
Prevalence of Anemia in Pregnant Women
After first dose of study drugs up to delivery or early termination
Incidence of Complicated Malaria in Infants
Birth up to 24 months of age or early study termination
- +5 more secondary outcomes
Study Arms (5)
3 dose SP pregnancy / 3 monthly DP infancy
ACTIVE COMPARATORWomen will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill 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. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug.
3 dose DP pregnancy / 3 monthly DP infancy
ACTIVE COMPARATORWomen will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill 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. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug.
3 dose DP pregnancy / monthly DP infancy
ACTIVE COMPARATORWomen will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill 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. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age.
monthly DP pregnancy / 3 monthly DP infancy
ACTIVE COMPARATORWomen will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill 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. Infants will be given DP (once a day for 3 consecutive days) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug.
monthly DP pregnancy / monthly DP infancy
ACTIVE COMPARATORWomen will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill 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. Infants will be given DP (once a day for 3 consecutive days) every 4 weeks between 8 and 104 weeks of age.
Interventions
Eligibility Criteria
You may qualify if:
- Pregnancy confirmed by positive urine pregnancy test or intrauterine pregnancy by ultrasound
- Estimated gestational age between 12-20 weeks
- Confirmed to be HIV uninfected by rapid test
- years of age or older
- Residency within 30km of the study clinic
- Provision of informed consent by the pregnant woman for herself and her unborn child
- Agreement to come to the study clinic for any febrile episode or other illness and avoid medications given outside the study protocol
- Plan 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 more than 30km from the study clinic
- Chronic medical condition requiring frequent medical attention
- Prior SP preventive therapy or any other antimalarial therapy during this pregnancy
- Early or active labor (documented by cervical change with uterine contractions)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
IDRC Research Clinic -Tororo District Hospital
Tororo, Uganda
Related Publications (11)
Kakuru A, Jagannathan P, Muhindo MK, Natureeba P, Awori P, Nakalembe M, Opira B, Olwoch P, Ategeka J, Nayebare P, Clark TD, Feeney ME, Charlebois ED, Rizzuto G, Muehlenbachs A, Havlir DV, Kamya MR, Dorsey G. Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy. N Engl J Med. 2016 Mar 10;374(10):928-39. doi: 10.1056/NEJMoa1509150.
PMID: 26962728RESULTMuhindo MK, Kakuru A, Natureeba P, Awori P, Olwoch P, Ategeka J, Nayebare P, Clark TD, Muehlenbachs A, Roh M, Mpeka B, Greenhouse B, Havlir DV, Kamya MR, Dorsey G, Jagannathan P. Reductions in malaria in pregnancy and adverse birth outcomes following indoor residual spraying of insecticide in Uganda. Malar J. 2016 Aug 26;15(1):437. doi: 10.1186/s12936-016-1489-x.
PMID: 27566109RESULTConrad MD, Mota D, Foster M, Tukwasibwe S, Legac J, Tumwebaze P, Whalen M, Kakuru A, Nayebare P, Wallender E, Havlir DV, Jagannathan P, Huang L, Aweeka F, Kamya MR, Dorsey G, Rosenthal PJ. Impact of Intermittent Preventive Treatment During Pregnancy on Plasmodium falciparum Drug Resistance-Mediating Polymorphisms in Uganda. J Infect Dis. 2017 Nov 15;216(8):1008-1017. doi: 10.1093/infdis/jix421.
PMID: 28968782RESULTKapisi J, Kakuru A, Jagannathan P, Muhindo MK, Natureeba P, Awori P, Nakalembe M, Ssekitoleko R, Olwoch P, Ategeka J, Nayebare P, Clark TD, Rizzuto G, Muehlenbachs A, Havlir DV, Kamya MR, Dorsey G, Gaw SL. Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes. Malar J. 2017 Oct 5;16(1):400. doi: 10.1186/s12936-017-2040-4.
PMID: 28982374RESULTJagannathan P, Kakuru A, Okiring J, Muhindo MK, Natureeba P, Nakalembe M, Opira B, Olwoch P, Nankya F, Ssewanyana I, Tetteh K, Drakeley C, Beeson J, Reiling L, Clark TD, Rodriguez-Barraquer I, Greenhouse B, Wallender E, Aweeka F, Prahl M, Charlebois ED, Feeney ME, Havlir DV, Kamya MR, Dorsey G. Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy and risk of malaria in early childhood: A randomized controlled trial. PLoS Med. 2018 Jul 17;15(7):e1002606. doi: 10.1371/journal.pmed.1002606. eCollection 2018 Jul.
PMID: 30016328RESULTMuhindo MK, Jagannathan P, Kakuru A, Opira B, Olwoch P, Okiring J, Nalugo N, Clark TD, Ruel T, Charlebois E, Feeney ME, Havlir DV, Dorsey G, Kamya MR. Intermittent preventive treatment with dihydroartemisinin-piperaquine and risk of malaria following cessation in young Ugandan children: a double-blind, randomised, controlled trial. Lancet Infect Dis. 2019 Sep;19(9):962-972. doi: 10.1016/S1473-3099(19)30299-3. Epub 2019 Jul 12.
PMID: 31307883RESULTConroy AL, Bangirana P, Muhindo MK, Kakuru A, Jagannathan P, Opoka RO, Liechty EA, Nakalembe M, Kamya MR, Dorsey G, John CC. Case Report: Birth Outcome and Neurodevelopment in Placental Malaria Discordant Twins. Am J Trop Med Hyg. 2019 Mar;100(3):552-555. doi: 10.4269/ajtmh.18-0659.
PMID: 30628574RESULTWallender E, Ali AM, Hughes E, Kakuru A, Jagannathan P, Muhindo MK, Opira B, Whalen M, Huang L, Duvalsaint M, Legac J, Kamya MR, Dorsey G, Aweeka F, Rosenthal PJ, Savic RM. Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children. Nat Commun. 2021 Nov 18;12(1):6714. doi: 10.1038/s41467-021-27051-8.
PMID: 34795281DERIVEDHughes E, Imperial M, Wallender E, Kajubi R, Huang L, Jagannathan P, Zhang N, Kakuru A, Natureeba P, Mwima MW, Muhindo M, Mwebaza N, Clark TD, Opira B, Nakalembe M, Havlir D, Kamya M, Rosenthal PJ, Dorsey G, Aweeka F, Savic RM. Piperaquine Exposure Is Altered by Pregnancy, HIV, and Nutritional Status in Ugandan Women. Antimicrob Agents Chemother. 2020 Nov 17;64(12):e01013-20. doi: 10.1128/AAC.01013-20. Print 2020 Nov 17.
PMID: 33020153DERIVEDWhalen ME, Kajubi R, Chamankhah N, Huang L, Orukan F, Wallender E, Kamya MR, Dorsey G, Jagannathan P, Rosenthal PJ, Mwebaza N, Aweeka FT. Reduced Exposure to Piperaquine, Compared to Adults, in Young Children Receiving Dihydroartemisinin-Piperaquine as Malaria Chemoprevention. Clin Pharmacol Ther. 2019 Dec;106(6):1310-1318. doi: 10.1002/cpt.1534. Epub 2019 Jul 22.
PMID: 31173649DERIVEDSavic RM, Jagannathan P, Kajubi R, Huang L, Zhang N, Were M, Kakuru A, Muhindo MK, Mwebaza N, Wallender E, Clark TD, Opira B, Kamya M, Havlir DV, Rosenthal PJ, Dorsey G, Aweeka FT. Intermittent Preventive Treatment for Malaria in Pregnancy: Optimization of Target Concentrations of Dihydroartemisinin-Piperaquine. Clin Infect Dis. 2018 Sep 14;67(7):1079-1088. doi: 10.1093/cid/ciy218.
PMID: 29547881DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Grant Dorsey
- Organization
- UCSF
Study Officials
- PRINCIPAL INVESTIGATOR
Grant Dorsey, MD, PhD
University of California, San Francisco
- PRINCIPAL INVESTIGATOR
Diane V Havlir, MD
University of California, San Francisco
- PRINCIPAL INVESTIGATOR
Moses Kamya, MBChB, MMed, PhD
Makerere University; Infectious Diseases Research Collaboration
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
June 5, 2014
First Posted
June 13, 2014
Study Start
June 23, 2014
Primary Completion
May 14, 2018
Study Completion
May 14, 2018
Last Updated
December 18, 2024
Results First Posted
November 14, 2018
Record last verified: 2024-12