MalariaPhase 3PROMOTE-BC3NCT02793622
Prevention of Malaria in HIV-uninfected Pregnant Women and Infants
A Phase 3 study testing Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy and Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy in people with Malaria, run by University of California, San Francisco at 1 site in Uganda.
Trial summary
This will be a double-blinded randomized controlled phase III trial of 782 HIV uninfected pregnant women and the children born to them. HIV uninfected women at 12-20 weeks gestation will be randomized in equal proportions to one of two intermittent preventive treatment in pregnancy (IPTp) treatment arms: 1) monthly… Read more about this study
- 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 Sulfadoxine-Pyrimethamine (SP) During Pregnancy and Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 782 participants
- Where
- 1 siteUganda
- Study dates
- Sep 2016to 4 Dec 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
- Resident of Busia District, Uganda
- 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 outside of Busia District, Uganda
- 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.
About this study
This will be a double-blinded randomized controlled phase III trial of 782 HIV uninfected pregnant women and the children born to them. HIV uninfected women at 12-20 weeks gestation will be randomized in equal proportions to one of two intermittent preventive treatment in pregnancy (IPTp) treatment arms: 1) monthly sulfadoxine-pyrimethamine (SP), or 2) monthly dihydroartemisinin-piperaquine (DP). Both interventions arms will have either SP or DP placebo to ensure adequate blinding is achieved in the study. Follow-up for the pregnant women will end approximately 6 weeks after giving birth. All children born to mothers enrolled in the study will be followed from birth until they reach 12 months of age.
Read the detailed description
Pregnant women will be scheduled to be seen in the clinic every 4 weeks during their pregnancy and then 1 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 at 1, 4, 6, and 8 weeks of age and then every 4 weeks until they reach 52 weeks of age. Parents/guardians will be instructed to bring their children 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. Study participants not seen in the clinic for their every 4 week routine visits will be visited at home and requested to come to the study clinic as soon as possible. Pregnant women and children will receive standard of care as designated in the Uganda Ministry of Health guidelines. Routine antenatal care will include screening and treatment for sexually transmitted infections, blood pressure assessment, urine dipstick for proteinuria, prescription of iron, folate, multivitamins and mebendazole. Routine care in children will include immunizations, vitamin A supplementation, and management of anemia using 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 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 (in very young children, heel sticks may be substituted for finger pricks), capillary plasma (for routine visits where phlebotomy is not done in pregnant women only) and filter paper samples. If a pregnant woman or parent/guardian of a child reports a fever in the last 24 hours or the patient has a documented temperature > 38.0˚C tympanic, the patient's thick blood smear will be read immediately and if positive the patient will be diagnosed and treated for 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. In pregnant mothers, thick blood smears other than those done when a mother has fever will not be used for clinical care of study participants. Phlebotomy for routine laboratory tests (CBC and ALT) to monitor for potential adverse events from study medications, storage of plasma and for immunology studies will be performed every 8 weeks in pregnant women. Phlebotomy for routine laboratory tests (CBC) and immunology studies will be performed at 12, 28, and 52 weeks of age in children. For pregnant women, study drugs will be administered at the time of each routine visit. ECGs will be performed to measure the QTc interval in all pregnant women just prior to the 1st dose of study drugs and 2-3 hours after their 3rd dose of study drugs at 20, 28 and 36 weeks of gestation. In addition a finger prick capillary plasma sample will be collected just prior to performing the ECGs after the 3rd dose of study drugs at 20, 28, and 36 weeks of gestation in pregnant women.
- Conditions
- Malaria
- Being tested
- Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy, Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
- Keywords
- Chemoprevention, Malaria, 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 Sulfadoxine-Pyrimethamine (SP) During PregnancyDrug
Also called Kamsidar (KPI)
Monthly Dihydroartemisinin-Piperaquine (DP) During PregnancyDrug
Also called Duo-Cotexin (Holley-Cotec)
| Study group | Role | What they receive |
|---|---|---|
| Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy | Active comparator | Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, 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) 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. Receives: Drug: Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy |
| Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy | 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 drugs on day 1 (SP and placebo or DP and placebo) 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. Receives: Drug: Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Deliver With a Composite Adverse Birth Outcome
Composite adverse birth outcome defined as any one of the following: 1) Low birth weight (< 2500 gm); 2) Preterm delivery (< 37 weeks gestational age); 3) Small for gestational age (< 10th percentile relative to an external growth reference)
Measured: Delivery
Incidence of Malaria in Infants
episodes per person year
Measured: Time at risk will begin at birth and end when study participants reaches 12 months of age or early study termination
Mean Gestational Age in Weeks at Birth
Gestational age in weeks determined by ultrasound dating (gold standard) and by the metabolic profiling outcome from biological specimens including placental tissue and placental blood.
Measured: At the time of delivery
Secondary outcomes (11)
Prevalence of Placental Malaria by Histology
Any evidence of placental infection (parasites or pigment). Number of participants with placental tissue positive for malaria parasites or pigment.
Measured: Delivery
Prevalence of Placental Parasitemia
Proportion of placental blood samples positive for parasites by Loop-mediated isothermal amplification (LAMP) or microscopy
Measured: Delivery
Prevalence of Maternal Malaria
Maternal blood positive for malaria parasites by microscopy.
Measured: Gestational age between 12-20 weeks (at study entry) up to delivery
Number of Participants With Adverse Events
All grade 3 and 4 adverse events
Measured: Starting at the time of their first study drug administration, approximately gestational age between 12-20 weeks, up to one month post-delivery
Prevalence of Anemia in Pregnant Women
hemoglobin < 11 g/dL
Measured: Starting at the time of their first study drug administration, approximately gestational age between 12-20 weeks, up to one month post-delivery
Prevalence of Anemia in Infants
Defined as the proportion with hemoglobin < 10 g/dL measure routinely at 12, 28, and 52 weeks of age. Number of cases per person year (PPY).
This is a prevalence measure but are repeated measures during infancy. In other words we measured this outcome up to 3 times for each participant during infancy (at 12, 28 and 52 weeks of age).
Measured: Birth up to 12 months of age or early termination
Prevalence of Asymptomatic Parasitemia in Pregnant Women
Proportion of routine monthly samples positive for parasites by microscopy and LAMP
Measured: Starting at the time of their first study drug administration, approximately gestational age between 12-20 weeks, up to one month post-delivery
Prevalence of Asymptomatic Parasitemia in Infants
Proportion of routine monthly samples positive for parasites by microscopy and LAMP
Measured: Birth up to 12 months of age or early termination
Incidence of Complicated Malaria in Infants
Complicated malaria defined as an episode of malaria with danger signs (any of the following: less than 3 convulsions over 24 h, inability to sit or stand, vomiting everything, unable to breastfeed or drink) or the meeting standardized criteria for severe malaria.
Measured: Birth up to 12 months of age or early termination
Incidence of Hospital Admissions in Infants
Admission to the pediatric ward for any cause
Measured: Birth up to 12 months of age or early termination
Infant Mortality Rate
Any deaths occurring after birth
Measured: Birth up to 12 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2016 (estimated)
- Study startSep 2016
- Primary completion4 Dec 2018
- Study completion4 Dec 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 (12)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- 782 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bill and Melinda Gates Foundation
- Responsible party
- Principal investigator, Grant Dorsey, M.D, Ph.D., University of California, San Francisco
- Investigators
- Grant Dorsey, MD PhD, Principal investigator, University of California, San FranciscoDiane V Havlir, MD, Principal investigator, University of California, San FranciscoMoses Kamya, MBChB MMed PhD, Principal investigator, Makarere Univeritys ; Infectious Disease Research Collaboration
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02793622
- Sponsor's protocol ID
- PROMOTE-BC3
- Acronym
- PROMOTE-BC3
- Status last verified
- Apr 2021
- First submitted
- 20 May 2016
- Last updated
- 14 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Kajubi R, Ochieng T, Kakuru A, Jagannathan P, Nakalembe M, Ruel T, Opira B, Ochokoru H, Ategeka J, Nayebare P, Clark TD, Havlir DV, Kamya MR, Dorsey G. Monthly sulfadoxine-pyrimethamine versus dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnancy: a double-blind, randomised, controlled, superiority trial. Lancet. 2019 Apr 6;393(10179):1428-1439. doi: 10.1016/S0140-6736(18)32224-4. Epub 2019 Mar 22.
PubMed 30910321Harrington WE, Kakuru A, Jagannathan P. Malaria in pregnancy shapes the development of foetal and infant immunity. Parasite Immunol. 2019 Mar;41(3):e12573. doi: 10.1111/pim.12573. Epub 2018 Aug 28.
PubMed 30019470Briggs J, Ategeka J, Kajubi R, Ochieng T, Kakuru A, Ssemanda C, Wasswa R, Jagannathan P, Greenhouse B, Rodriguez-Barraquer I, Kamya M, Dorsey G. Impact of Microscopic and Submicroscopic Parasitemia During Pregnancy on Placental Malaria in a High-Transmission Setting in Uganda. J Infect Dis. 2019 Jul 2;220(3):457-466. doi: 10.1093/infdis/jiz130.
PubMed 30891605Okiring J, Olwoch P, Kakuru A, Okou J, Ochokoru H, Ochieng TA, Kajubi R, Kamya MR, Dorsey G, Tusting LS. Household and maternal risk factors for malaria in pregnancy in a highly endemic area of Uganda: a prospective cohort study. Malar J. 2019 Apr 23;18(1):144. doi: 10.1186/s12936-019-2779-x.
PubMed 31014336Kakuru A, Jagannathan P, Kajubi R, Ochieng T, Ochokoru H, Nakalembe M, Clark TD, Ruel T, Staedke SG, Chandramohan D, Havlir DV, Kamya MR, Dorsey G. Impact of intermittent preventive treatment of malaria in pregnancy with dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine on the incidence of malaria in infancy: a randomized controlled trial. BMC Med. 2020 Aug 10;18(1):207. doi: 10.1186/s12916-020-01675-x.
PubMed 32772921Savic 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 29547881Ategeka J, Kakuru A, Kajubi R, Wasswa R, Ochokoru H, Arinaitwe E, Yeka A, Jagannathan P, Kamya MR, Muehlenbachs A, Chico RM, Dorsey G. Relationships Between Measures of Malaria at Delivery and Adverse Birth Outcomes in a High-Transmission Area of Uganda. J Infect Dis. 2020 Aug 4;222(5):863-870. doi: 10.1093/infdis/jiaa156.
PubMed 32249917Roh ME, Kuile FOT, Rerolle F, Glymour MM, Shiboski S, Gosling R, Gutman J, Kakuru A, Desai M, Kajubi R, L'Ianziva A, Kamya MR, Dorsey G, Chico RM. Overall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine on birthweight: a mediation analysis. Lancet Glob Health. 2020 Jul;8(7):e942-e953. doi: 10.1016/S2214-109X(20)30119-4.
PubMed 32562650Vaaben AV, Levan J, Nguyen CBT, Callaway PC, Prahl M, Warrier L, Nankya F, Musinguzi K, Kakuru A, Muhindo MK, Dorsey G, Kamya MR, Feeney ME. In Utero Activation of Natural Killer Cells in Congenital Cytomegalovirus Infection. J Infect Dis. 2022 Sep 4;226(4):566-575. doi: 10.1093/infdis/jiac307.
PubMed 35876164Hughes E, Wallender E, Kajubi R, Jagannathan P, Ochieng T, Kakuru A, Kamya MR, Clark TD, Rosenthal PJ, Dorsey G, Aweeka F, Savic RM. Piperaquine-Induced QTc Prolongation Decreases With Repeated Monthly Dihydroartemisinin-Piperaquine Dosing in Pregnant Ugandan Women. Clin Infect Dis. 2022 Aug 31;75(3):406-415. doi: 10.1093/cid/ciab965.
PubMed 34864925Zehner N, Adrama H, Kakuru A, Andra T, Kajubi R, Conrad M, Nankya F, Clark TD, Kamya M, Rodriguez-Barraquer I, Dorsey G, Jagannathan P. Age-Related Changes in Malaria Clinical Phenotypes During Infancy Are Modified by Sickle Cell Trait. Clin Infect Dis. 2021 Nov 16;73(10):1887-1895. doi: 10.1093/cid/ciab245.
PubMed 33738485Kakuru A, Roh ME, Kajubi R, Ochieng T, Ategeka J, Ochokoru H, Nakalembe M, Clark TD, Ruel T, Staedke SG, Chandramohan D, Havlir DV, Kamya MR, Dorsey G, Jagannathan P. Infant sex modifies associations between placental malaria and risk of malaria in infancy. Malar J. 2020 Dec 3;19(1):449. doi: 10.1186/s12936-020-03522-z.
PubMed 33272281
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Malaria in HIV-uninfected Pregnant Women and Infants
- ClinicalTrials.gov ID
- NCT02793622
- Acronym / sponsor ID
- PROMOTE-BC3 / PROMOTE-BC3
- Conditions
- Malaria
- Keywords
- Chemoprevention, Malaria, Sulfadoxine-Pyrimethamine, Dihydroartemisinin-Piperaquine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 782 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bill and Melinda Gates Foundation
- Study start
- Sep 2016
- Primary completion
- 4 Dec 2018 (actual)
- Study completion
- 4 Dec 2018 (actual)
- First posted
- 8 Jun 2016 (estimated)
- Results
- Posted 14 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a double-blinded randomized controlled phase III trial of 782 HIV uninfected pregnant women and the children born to them. HIV uninfected women at 12-20 weeks gestation will be randomized in equal proportions to one of two intermittent preventive treatment in pregnancy (IPTp) treatment arms: 1) monthly sulfadoxine-pyrimethamine (SP), or 2) monthly dihydroartemisinin-piperaquine (DP). Both interventions arms will have either SP or DP placebo to ensure adequate blinding is achieved in the study. Follow-up for the pregnant women will end approximately 6 weeks after giving birth. All children born to mothers enrolled in the study will be followed from birth until they reach 12 months of age.
Detailed description
Pregnant women will be scheduled to be seen in the clinic every 4 weeks during their pregnancy and then 1 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 at 1, 4, 6, and 8 weeks of age and then every 4 weeks until they reach 52 weeks of age. Parents/guardians will be instructed to bring their children 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. Study participants not seen in the clinic for their every 4 week routine visits will be visited at home and requested to come to the study clinic as soon as possible. Pregnant women and children will receive standard of care as designated in the Uganda Ministry of Health guidelines. Routine antenatal care will include screening and treatment for sexually transmitted infections, blood pressure assessment, urine dipstick for proteinuria, prescription of iron, folate, multivitamins and mebendazole. Routine care in children will include immunizations, vitamin A supplementation, and management of anemia using 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 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 (in very young children, heel sticks may be substituted for finger pricks), capillary plasma (for routine visits where phlebotomy is not done in pregnant women only) and filter paper samples. If a pregnant woman or parent/guardian of a child reports a fever in the last 24 hours or the patient has a documented temperature > 38.0˚C tympanic, the patient's thick blood smear will be read immediately and if positive the patient will be diagnosed and treated for 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. In pregnant mothers, thick blood smears other than those done when a mother has fever will not be used for clinical care of study participants. Phlebotomy for routine laboratory tests (CBC and ALT) to monitor for potential adverse events from study medications, storage of plasma and for immunology studies will be performed every 8 weeks in pregnant women. Phlebotomy for routine laboratory tests (CBC) and immunology studies will be performed at 12, 28, and 52 weeks of age in children. For pregnant women, study drugs will be administered at the time of each routine visit. ECGs will be performed to measure the QTc interval in all pregnant women just prior to the 1st dose of study drugs and 2-3 hours after their 3rd dose of study drugs at 20, 28 and 36 weeks of gestation. In addition a finger prick capillary plasma sample will be collected just prior to performing the ECGs after the 3rd dose of study drugs at 20, 28, and 36 weeks of gestation in pregnant women.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy | Active comparator | Drug: Monthly Sulfadoxine-Pyrimethamine (SP) During PregnancyWomen will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, 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) 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. |
| Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy | Active comparator | Drug: Monthly Dihydroartemisinin-Piperaquine (DP) During PregnancyWomen 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 drugs on day 1 (SP and placebo or DP and placebo) 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. |
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
- Resident of Busia District, Uganda
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 outside of Busia District, Uganda
- 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 Sulfadoxine-Pyrimethamine (SP) During PregnancyAlso: Kamsidar (KPI) | Drug | Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy |
| Monthly Dihydroartemisinin-Piperaquine (DP) During PregnancyAlso: Duo-Cotexin (Holley-Cotec) | Drug | Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy |
Primary outcome
Number of Participants Who Deliver With a Composite Adverse Birth Outcome
Time frame: Delivery
Composite adverse birth outcome defined as any one of the following: 1) Low birth weight (< 2500 gm); 2) Preterm delivery (< 37 weeks gestational age); 3) Small for gestational age (< 10th percentile relative to an external growth reference)
Incidence of Malaria in Infants
Time frame: Time at risk will begin at birth and end when study participants reaches 12 months of age or early study termination
episodes per person year
Mean Gestational Age in Weeks at Birth
Time frame: At the time of delivery
Gestational age in weeks determined by ultrasound dating (gold standard) and by the metabolic profiling outcome from biological specimens including placental tissue and placental blood.
11 secondary outcomes
Prevalence of Placental Malaria by Histology
Time frame: Delivery
Prevalence of Placental Parasitemia
Time frame: Delivery
Prevalence of Maternal Malaria
Time frame: Gestational age between 12-20 weeks (at study entry) up to delivery
Number of Participants With Adverse Events
Time frame: Starting at the time of their first study drug administration, approximately gestational age between 12-20 weeks, up to one month post-delivery
Prevalence of Anemia in Pregnant Women
Time frame: Starting at the time of their first study drug administration, approximately gestational age between 12-20 weeks, up to one month post-delivery
Prevalence of Anemia in Infants
Time frame: Birth up to 12 months of age or early termination
Prevalence of Asymptomatic Parasitemia in Pregnant Women
Time frame: Starting at the time of their first study drug administration, approximately gestational age between 12-20 weeks, up to one month post-delivery
Prevalence of Asymptomatic Parasitemia in Infants
Time frame: Birth up to 12 months of age or early termination
Incidence of Complicated Malaria in Infants
Time frame: Birth up to 12 months of age or early termination
Incidence of Hospital Admissions in Infants
Time frame: Birth up to 12 months of age or early termination
Infant Mortality Rate
Time frame: Birth up to 12 months of age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30910321Kajubi R, Ochieng T, Kakuru A, Jagannathan P, Nakalembe M, Ruel T, Opira B, Ochokoru H, Ategeka J, Nayebare P, Clark TD, Havlir DV, Kamya MR, Dorsey G. Monthly sulfadoxine-pyrimethamine versus dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnancy: a double-blind, randomised, controlled, superiority trial. Lancet. 2019 Apr 6;393(10179):1428-1439. doi: 10.1016/S0140-6736(18)32224-4. Epub 2019 Mar 22.
- Results publication: PubMed 30019470Harrington WE, Kakuru A, Jagannathan P. Malaria in pregnancy shapes the development of foetal and infant immunity. Parasite Immunol. 2019 Mar;41(3):e12573. doi: 10.1111/pim.12573. Epub 2018 Aug 28.
- Results publication: PubMed 30891605Briggs J, Ategeka J, Kajubi R, Ochieng T, Kakuru A, Ssemanda C, Wasswa R, Jagannathan P, Greenhouse B, Rodriguez-Barraquer I, Kamya M, Dorsey G. Impact of Microscopic and Submicroscopic Parasitemia During Pregnancy on Placental Malaria in a High-Transmission Setting in Uganda. J Infect Dis. 2019 Jul 2;220(3):457-466. doi: 10.1093/infdis/jiz130.
- Results publication: PubMed 31014336Okiring J, Olwoch P, Kakuru A, Okou J, Ochokoru H, Ochieng TA, Kajubi R, Kamya MR, Dorsey G, Tusting LS. Household and maternal risk factors for malaria in pregnancy in a highly endemic area of Uganda: a prospective cohort study. Malar J. 2019 Apr 23;18(1):144. doi: 10.1186/s12936-019-2779-x.
- Results publication: PubMed 32772921Kakuru A, Jagannathan P, Kajubi R, Ochieng T, Ochokoru H, Nakalembe M, Clark TD, Ruel T, Staedke SG, Chandramohan D, Havlir DV, Kamya MR, Dorsey G. Impact of intermittent preventive treatment of malaria in pregnancy with dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine on the incidence of malaria in infancy: a randomized controlled trial. BMC Med. 2020 Aug 10;18(1):207. doi: 10.1186/s12916-020-01675-x.
- Results publication: 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.
- Results publication: PubMed 32249917Ategeka J, Kakuru A, Kajubi R, Wasswa R, Ochokoru H, Arinaitwe E, Yeka A, Jagannathan P, Kamya MR, Muehlenbachs A, Chico RM, Dorsey G. Relationships Between Measures of Malaria at Delivery and Adverse Birth Outcomes in a High-Transmission Area of Uganda. J Infect Dis. 2020 Aug 4;222(5):863-870. doi: 10.1093/infdis/jiaa156.
- Results publication: PubMed 32562650Roh ME, Kuile FOT, Rerolle F, Glymour MM, Shiboski S, Gosling R, Gutman J, Kakuru A, Desai M, Kajubi R, L'Ianziva A, Kamya MR, Dorsey G, Chico RM. Overall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine on birthweight: a mediation analysis. Lancet Glob Health. 2020 Jul;8(7):e942-e953. doi: 10.1016/S2214-109X(20)30119-4.
- Derived from this study: PubMed 35876164Vaaben AV, Levan J, Nguyen CBT, Callaway PC, Prahl M, Warrier L, Nankya F, Musinguzi K, Kakuru A, Muhindo MK, Dorsey G, Kamya MR, Feeney ME. In Utero Activation of Natural Killer Cells in Congenital Cytomegalovirus Infection. J Infect Dis. 2022 Sep 4;226(4):566-575. doi: 10.1093/infdis/jiac307.
- Derived from this study: PubMed 34864925Hughes E, Wallender E, Kajubi R, Jagannathan P, Ochieng T, Kakuru A, Kamya MR, Clark TD, Rosenthal PJ, Dorsey G, Aweeka F, Savic RM. Piperaquine-Induced QTc Prolongation Decreases With Repeated Monthly Dihydroartemisinin-Piperaquine Dosing in Pregnant Ugandan Women. Clin Infect Dis. 2022 Aug 31;75(3):406-415. doi: 10.1093/cid/ciab965.
- Derived from this study: PubMed 33738485Zehner N, Adrama H, Kakuru A, Andra T, Kajubi R, Conrad M, Nankya F, Clark TD, Kamya M, Rodriguez-Barraquer I, Dorsey G, Jagannathan P. Age-Related Changes in Malaria Clinical Phenotypes During Infancy Are Modified by Sickle Cell Trait. Clin Infect Dis. 2021 Nov 16;73(10):1887-1895. doi: 10.1093/cid/ciab245.
- Derived from this study: PubMed 33272281Kakuru A, Roh ME, Kajubi R, Ochieng T, Ategeka J, Ochokoru H, Nakalembe M, Clark TD, Ruel T, Staedke SG, Chandramohan D, Havlir DV, Kamya MR, Dorsey G, Jagannathan P. Infant sex modifies associations between placental malaria and risk of malaria in infancy. Malar J. 2020 Dec 3;19(1):449. doi: 10.1186/s12936-020-03522-z.
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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
Makarere Univeritys ; Infectious Disease Research Collaboration
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy and Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy in people with Malaria, run by University of California, San Francisco at 1 site in Uganda.
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 14 Apr 2021. 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 Apr 2021). 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?
Number of Participants Who Deliver With a Composite Adverse Birth Outcome (time frame: Delivery). The study lists 3 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 NCT02793622, which also lists 12 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 14 Apr 2021.