MalariaPhase 3PROMOTE-BC1NCT02163447

Reducing the Burden of Malaria in HIV-uninfected Pregnant Women and Infants

A Phase 3 study testing Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy, 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy and 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy in people with Malaria, run by Grant Dorsey, M.D, Ph.D. at 1 site in Uganda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 16 years and older, women onlyHealthy volunteers can take part
Conditions the study is for: Malaria
What is being tested?: Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy, 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy and 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 300 participants
Where: 1 siteUganda
Study dates: 23 Jun 2014to 14 May 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 years and older
Women only
Healthy volunteers accepted
Child, Adult, Older adult

Who may be able to join

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
16 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

Who cannot join

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)

Trial locations and contacts

1 site in 1 country.

Uganda1 site

IDRC Research Clinic -Tororo District Hospital
Tororo

Other trials in Uganda

About this study

Official title: Reducing the Burden of Malaria in HIV-uninfected Pregnant Women and Infants (PROMOTE Birth Cohort 1)

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.

Read the detailed description

Pregnant women will be scheduled to be seen in the clinic every 4 weeks during their pregnancy and 6 weeks following delivery. In addition, pregnant women will be instructed to come to the study clinic for all their medical care and avoid the use of any outside medications. Children will be scheduled to be seen in the clinic every 4 weeks and parents /guardians of children will be instructed to bring their child to the study clinic for all medical care and avoid the use of any outside medications. The study clinic will remain open 7 days a week from 8 a.m. to 5 p.m.

Each time a study participant is seen in the clinic a standardized history and physical exam will be performed. Patients who are febrile (tympanic temperature > 3 8.0˚C) or report history of fever in the past 24 hours will have blood obtained by finger prick for a thick blood smear. If the thick blood smear is positive, the patient will be diagnosed with malaria. If the thick blood smear is negative, the patient will be managed by study physicians for a non-malarial febrile illness. If the patient is afebrile and does not report a recent fever, a thick blood smear will not be obtained, except when following routine testing schedules.

Routine assessments will be done in the clinic every 4 weeks for both pregnant women and children. Pregnant women and children will receive standards of care as designated in the Uganda MOH guidelines. Routine care in children will use Integrated Management of Childhood Illness (IMCI) guidelines. During routine assessments subjects will be asked about visits to outside health facilities and the use of any medications outside the study protocol. Standardized assessment of adherence will also be done for study drugs administered at home and Insecticide Treated Net use. A routine history and physical exam will be performed using a standardized clinical assessment form. Blood will be collected by finger prick for thick smear, collection of plasma for PK studies, and filter paper samples. Phlebotomy for routine laboratory tests (CBC and ALT) to monitor for potential adverse events from study medications and for immunology studies will be performed every 8 weeks in pregnant women and every 16 weeks in children. Non malaria screening will also include stool ova and parasite examination, circulating filarial antigens (by ICT card for Wucheria), and blood smear for microfilaremia (including Mansonella perstans) using Knott's technique. For pregnant women and children 2-24 months of age, study drugs will be administered at the time of each routine visit.

Conditions: Malaria
Being tested: Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy, 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy, 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy, Monthly dihydroartemisinin-piperaquine (DP) for infants, 3-monthly dihydroartemisinin-piperaquine (DP) for infants
Keywords: Chemoprevention, Malaria, Uganda, Sulfadoxine-pyrimethamine, Dihydroartemisinin-piperaquine
Medical subject headings: Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancyDrug
Also called Duo-Cotexin (Holley-Cotec)
3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancyDrug
Also called Duo-Cotexin (Holley-Cotec)
3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancyDrug
Also called Kamsidar (KPI)
Monthly dihydroartemisinin-piperaquine (DP) for infantsDrug
Also called Duo-Cotexin (Holley-Cotec)
3-monthly dihydroartemisinin-piperaquine (DP) for infantsDrug
Also called Duo-Cotexin (Holley-Cotec)

Study groups in NCT02163447
Study group	Role	What they receive
3 dose SP pregnancy / 3 monthly DP infancy	Active comparator	Women 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. Receives: Drug: 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy; Drug: 3-monthly dihydroartemisinin-piperaquine (DP) for infants
3 dose DP pregnancy / 3 monthly DP infancy	Active comparator	Women 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. Receives: Drug: 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; Drug: 3-monthly dihydroartemisinin-piperaquine (DP) for infants
3 dose DP pregnancy / monthly DP infancy	Active comparator	Women 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. Receives: Drug: 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; Drug: Monthly dihydroartemisinin-piperaquine (DP) for infants
monthly DP pregnancy / 3 monthly DP infancy	Active comparator	Women 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. Receives: Drug: Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; Drug: 3-monthly dihydroartemisinin-piperaquine (DP) for infants
monthly DP pregnancy / monthly DP infancy	Active comparator	Women 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. Receives: Drug: Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; Drug: Monthly dihydroartemisinin-piperaquine (DP) for infants

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Prevalence of placental blood samples positive for parasites by microscopy or LAMP
Measured: Delivery
Number of Participants With Maternal Blood Samples Positive for Parasites by Microscopy and LAMP at Delivery
Prevalence of maternal parasitemia at delivery by microscopy and LAMP
Measured: At delivery
Number of Participants With One or More Birth Outcomes: Congenital Malformations, Spontaneous Abortion, LBW (<2500g), Still Birth, Pre-term Delivery
Congenital malformations, spontaneous abortion, LBW (<2500g), still birth, pre-term delivery
Measured: Delivery
Prevalence of Anemia in Pregnant Women
Prevalence of routine hemoglobin measurements < 11 g/dL
Measured: After first dose of study drugs up to delivery or early termination
Incidence of Complicated Malaria in Infants
Any treatment for malaria meeting criteria for severe malaria or danger signs
Measured: Birth up to 24 months of age or early study termination
Incidence of Hospital Admissions in Infants
Admission to a hospital for pediatric inpatient care for any reason
Measured: Birth up to 24 months of age or early study termination
Prevalence of Gametocytemia in Pregnant Women
Proportion of urgent blood smears positive for gametocytes
Measured: Gestational age between 12-20 weeks (at study entry) up to delivery
Prevalence of Parasitemia in Infants
Proportion of routine monthly samples positive for parasites by LAMP. Proportion of routine samples (LAMP or blood smears) positive for asexual parasites.
Measured: Birth up to 24 months of age or early study termination
Prevalence of Parasitemia at the Time of Monthly Routine Visits During Pregnancy
Detection of malaria parasites by LAMP during pregnancy
Measured: After first dose of study drug through delivery or early termination
Prevalence of Gametocytemia in Infants
Proportion of routine blood smears positive for gametocytes
Measured: Birth up to 24 months of age or early study termination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jun 201414 May 2018

First posted13 Jun 2014 (estimated)
Study start23 Jun 2014
Primary completion14 May 2018
Study completion14 May 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (11)Papers the sponsor has linked to this study.
Other trials for MalariaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 300 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02163447
Sponsor's protocol ID: PROMOTE-BC1
Other IDs: P01HD059454
Acronym: PROMOTE-BC1
Status last verified: Dec 2024
First submitted: 5 Jun 2014
Last updated: 18 Dec 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 26962728
Muhindo 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.
PubMed 27566109
Conrad 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.
PubMed 28968782
Kapisi 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.
PubMed 28982374
Jagannathan 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.
PubMed 30016328
Muhindo 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.
PubMed 31307883
Conroy 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.
PubMed 30628574
Wallender 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.
PubMed 34795281
Hughes 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.
PubMed 33020153
Whalen 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.
PubMed 31173649
Savic 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.
PubMed 29547881

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Reducing the Burden of Malaria in HIV-uninfected Pregnant Women and Infants (PROMOTE Birth Cohort 1)
ClinicalTrials.gov ID: NCT02163447
Acronym / sponsor ID: PROMOTE-BC1 / PROMOTE-BC1
Conditions: Malaria
Keywords: Chemoprevention, Malaria, Uganda, Sulfadoxine-pyrimethamine, Dihydroartemisinin-piperaquine
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 300 participants (actual)
Lead sponsor: Grant Dorsey, M.D, Ph.D.University, hospital or other
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study start: 23 Jun 2014 (actual)
Primary completion: 14 May 2018 (actual)
Study completion: 14 May 2018 (actual)
First posted: 13 Jun 2014 (estimated)
Results: Posted 14 Nov 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
3 dose SP pregnancy / 3 monthly DP infancy	Active comparator	Drug: 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy, Drug: 3-monthly dihydroartemisinin-piperaquine (DP) for infantsWomen 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 comparator	Drug: 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy, Drug: 3-monthly dihydroartemisinin-piperaquine (DP) for infantsWomen 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 comparator	Drug: 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy, Drug: Monthly dihydroartemisinin-piperaquine (DP) for infantsWomen 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 comparator	Drug: Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy, Drug: 3-monthly dihydroartemisinin-piperaquine (DP) for infantsWomen 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 comparator	Drug: Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy, Drug: Monthly dihydroartemisinin-piperaquine (DP) for infantsWomen 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.

Who may qualify

Ages: 16 years and older
Sex: Female only
Healthy volunteers: Accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

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
16 years of age or older
Residency within 30km of the study clinic

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancyAlso: Duo-Cotexin (Holley-Cotec)	Drug	monthly DP pregnancy / 3 monthly DP infancy, monthly DP pregnancy / monthly DP infancy
3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancyAlso: Duo-Cotexin (Holley-Cotec)	Drug	3 dose DP pregnancy / 3 monthly DP infancy, 3 dose DP pregnancy / monthly DP infancy
3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancyAlso: Kamsidar (KPI)	Drug	3 dose SP pregnancy / 3 monthly DP infancy
Monthly dihydroartemisinin-piperaquine (DP) for infantsAlso: Duo-Cotexin (Holley-Cotec)	Drug	3 dose DP pregnancy / monthly DP infancy, monthly DP pregnancy / monthly DP infancy
3-monthly dihydroartemisinin-piperaquine (DP) for infantsAlso: Duo-Cotexin (Holley-Cotec)	Drug	3 dose DP pregnancy / 3 monthly DP infancy, 3 dose SP pregnancy / 3 monthly DP infancy, monthly DP pregnancy / 3 monthly DP infancy

Primary outcome

Prevalence of Placental Malaria
Time frame: Delivery
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.
Incidence of Malaria in Pregnant Women
Time frame: 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, 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.
Incidence of Malaria in Infants
Time frame: 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)
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.
Incidence of Malaria in Infants
Time frame: Time at risk will begin at 24 months of age and will end when study participants reaches 36 months of age or termination
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.

10 secondary outcomes

Number of Participants With Blood Samples Positive for Parasites by Microscopy or LAMP
Time frame: Delivery
Number of Participants With Maternal Blood Samples Positive for Parasites by Microscopy and LAMP at Delivery
Time frame: At delivery
Number of Participants With One or More Birth Outcomes: Congenital Malformations, Spontaneous Abortion, LBW (<2500g), Still Birth, Pre-term Delivery
Time frame: Delivery
Prevalence of Anemia in Pregnant Women
Time frame: After first dose of study drugs up to delivery or early termination
Incidence of Complicated Malaria in Infants
Time frame: Birth up to 24 months of age or early study termination
Incidence of Hospital Admissions in Infants
Time frame: Birth up to 24 months of age or early study termination
Prevalence of Gametocytemia in Pregnant Women
Time frame: Gestational age between 12-20 weeks (at study entry) up to delivery
Prevalence of Parasitemia in Infants
Time frame: Birth up to 24 months of age or early study termination
Prevalence of Parasitemia at the Time of Monthly Routine Visits During Pregnancy
Time frame: After first dose of study drug through delivery or early termination
Prevalence of Gametocytemia in Infants
Time frame: Birth up to 24 months of age or early study termination

Results and safety

Results posted to the registry on 14 Nov 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Mothers - 3 Dose SP	106	100
Mothers - 3 Dose DP	94	88
Mothers - Monthly DP	100	97

Primary outcome: Prevalence of Placental Malaria

Time frame: Delivery. Count of participants. Unit: Participants

Measure	Mothers - 3 Dose SP n = 98	Mothers - 3 Dose DP n = 88	Mothers - Monthly DP n = 96
Value	49	30	26

Population analysed: Only women who delivered and had histopathology results were analyzed. 2 women in 3 Dose SP and 1 woman in monthly DP arms completed the study but did not have histopathology results.

Primary outcome: Incidence of Malaria in Pregnant Women

Time frame: Time at risk will begin after first dose of study drug and will end when study participants deliver or early study termination. Number. Unit: events per person years

Measure	Mothers - 3 Dose SP n = 106	Mothers - 3 Dose DP n = 94	Mothers - Monthly DP n = 100
Value	0.95	0.31	0

Primary outcome: Incidence of Malaria in Infants

Time frame: 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). Number. Unit: Events per person years

Measure	3 Dose SP Pregnancy / 3 Monthly DP Infancy n = 101	3 Dose DP Pregnancy / 3 Monthly DP Infancy n = 44	3 Dose DP Pregnancy / Monthly DP Infancy n = 49	Monthly DP Pregnancy / 3 Monthly DP Infancy n = 48	Monthly DP Pregnancy / Monthly DP Infancy n = 52
Value	0.26	0.30	0.00	0.43	0.03

Population analysed: All live births

Primary outcome: Incidence of Malaria in Infants

Time frame: Time at risk will begin at 24 months of age and will end when study participants reaches 36 months of age or termination. Number. Unit: Events per person years

Measure	3 Dose SP Pregnancy / 3 Monthly DP Infancy n = 85	3 Dose DP Pregnancy / 3 Monthly DP Infancy n = 40	3 Dose DP Pregnancy / Monthly DP Infancy n = 43	Monthly DP Pregnancy / 3 Monthly DP Infancy n = 39	Monthly DP Pregnancy / Monthly DP Infancy n = 44
Value	0.87	0.88	0.83	1.24	0.64

Population analysed: All live births

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: For women, from study drug initiation to 6 weeks postpartum or last observed date in study. For children, from study drug initiation to 4 weeks after last dose of study drugs.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Mothers - 3 Dose SP	6 of 106 (5.7%)	90 of 106 (84.9%)	0 of 106
Mothers - 3 Dose DP	9 of 94 (9.6%)	78 of 94 (83%)	0 of 94
Mothers - Monthly DP	3 of 100 (3%)	89 of 100 (89%)	0 of 100
Infants - Monthly DP	9 of 100 (9%)	94 of 100 (94%)	4 of 100
Infants - 3 Monthly DP	15 of 191 (7.9%)	183 of 191 (95.8%)	3 of 191

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26962728Kakuru 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.
Results publication: PubMed 27566109Muhindo 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.
Results publication: PubMed 28968782Conrad 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.
Results publication: PubMed 28982374Kapisi 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.
Results publication: PubMed 30016328Jagannathan 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.
Results publication: PubMed 31307883Muhindo 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.
Results publication: PubMed 30628574Conroy 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.
Derived from this study: PubMed 34795281Wallender 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.
Derived from this study: PubMed 33020153Hughes 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.
Derived from this study: PubMed 31173649Whalen 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.
Derived from this study: PubMed 29547881Savic 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Grant Dorsey, MD, PhD principal investigator

University of California, San Francisco

Diane V Havlir, MD principal investigator

University of California, San Francisco

Moses Kamya, MBChB, MMed, PhD principal investigator

Makerere University; Infectious Diseases Research Collaboration

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prevalence of Placental Malaria (time frame: Delivery). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02163447, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.