MalariaPhase 3NCT02282293
Reducing the Burden of Malaria in HIV-Infected Pregnant Women and Their HIV-Exposed Children (PROMOTE-BC2)
A Phase 3 study testing Monthly dihydroartemisinin-piperaquine (DP) + daily trimethoprim/sulfamethoxazole (TS) in people with Malaria and Human Immunodeficiency Virus, run by University of California, San Francisco at 1 site in Uganda.
Trial summary
This is a double-blinded, randomized controlled trial of 200 HIV-infected pregnant women living in Tororo, Uganda, an area of high malaria transmission. HIV-infected pregnant women between 12 and 28 weeks gestation will be randomized to receive enhanced malaria chemoprevention with 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, Human Immunodeficiency Virus
- What is being tested?
- Monthly dihydroartemisinin-piperaquine (DP) + daily trimethoprim/sulfamethoxazole (TS)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUganda
- Study dates
- 9 Dec 2014to 26 May 2016
- 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
- Intrauterine pregnancy confirmed by ultrasound
- Estimated gestational age between 12-28 weeks
- Confirmed to be HIV-infected by Uganda country standard rapid HIV test
- 16 years of age or older
- Residency within 30 km of the study clinic
- Provision of informed consent
- Agreement to come to the study clinic for any febrile episode or other illness and avoid medications given outside the study protocol
- Plan to deliver in the hospital
Who cannot join
- History of serious adverse event to TS or DP
- Refusal to take cART during pregnancy or as part of routine HIV care
- Active medical problem requiring inpatient evaluation at the time of screening
- Intention of moving more than 30 km from the study clinic
- Active WHO stage 4 condition not stable under treatment
- Signs or symptoms of early or active labor
Show all 10Show fewer
- Currently on ritonavir
- Currently taking drugs associated with known risk of Torsades de pointes
- Currently taking CYP3A inhibitor medications which potentially inhibit the metabolism of piperaquine
- History of cardiac problems or fainting
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Reducing the Burden of Malaria in HIV-Infected Pregnant Women and Their HIV-Exposed Children (PROMOTE Birth Cohort 2)
This is a double-blinded, randomized controlled trial of 200 HIV-infected pregnant women living in Tororo, Uganda, an area of high malaria transmission. HIV-infected pregnant women between 12 and 28 weeks gestation will be randomized to receive enhanced malaria chemoprevention with monthly dihydroartemisinin-piperaquine (DP) versus monthly DP placebo. Their HIV-exposed children will receive the same prevention regimen from 2 to 24 months of age to which the mothers were randomized. All women will receive daily trimethoprim-sulfamethoxazole (TS) throughout the study per Uganda Ministry of Health guidelines. Children will also receive daily TS from 6 weeks to 24 months of age. TS will be considered a study drug only in infants and children beginning 6 weeks after cessation of breastfeeding and upon exclusion of HIV infection. Women and their children will be followed for 36 months after delivery. In a subset of the study population, the investigators will conduct an intensive pharmacokinetic study that will evaluate pharmacokinetic exposure of DP and EFV. The investigators will also measure HIV-related outcomes among the women enrolled in the study. The investigators will test the hypothesis that for HIV-infected mothers and HIV-exposed infants, that enhanced versus standard malaria chemoprevention in HIV-infected pregnant women and their children will reduce the incidence of malaria among children from 0 to 24 months of age and improve the development of naturally acquired antimalarial immunity.
Read the detailed description
Pregnant women will be scheduled to be seen in the study clinic every 4 weeks during their pregnancy. Women will be seen at 1 week, 6 weeks, and 3 months postpartum and every 3 months thereafter. 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. Women will be provided all routine HIV care at the clinic according to Uganda MOH guidelines. All women will have ARVs and TS dispensed at the study clinic. Counseling on breastfeeding and infant feeding will be provided per Uganda MOH guidelines. HIV care and breastfeeding and infant feeding recommendations may be changed to reflect the most recent standard of care per MOH guidelines. 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. Children will have care for HIV-exposed children according to MOH guidelines, with the exception that TS will be continued until 2 years of life. 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. 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, study drugs will be administered at the time of each routine visit.
- Conditions
- Malaria, Human Immunodeficiency Virus
- Being tested
- Monthly dihydroartemisinin-piperaquine (DP) + daily trimethoprim/sulfamethoxazole (TS), Monthly placebo + daily trimethoprim/sulfamethoxazole (TS)
- Keywords
- Chemoprevention, Malaria, Uganda, Dihydroartemisinin-piperaquine, Trimethoprim-sulfamethoxazole, Human Immunodeficiency Virus
- Medical subject headings
- Malaria, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Monthly dihydroartemisinin-piperaquine (DP) + daily trimethoprim/sulfamethoxazole (TS)Drug
Also called Duo-Cotexin (Holley-Cotec)
Monthly placebo + daily trimethoprim/sulfamethoxazole (TS)Drug
| Study group | Role | What they receive |
|---|---|---|
| Daily TS + Monthly DP 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. During pregancy, TS will be given to women at a dose of 960mg once daily. Receives: Drug: Monthly dihydroartemisinin-piperaquine (DP) + daily trimethoprim/sulfamethoxazole (TS) |
| Daily TS + DP Placebo pregnancy | Placebo comparator | Women will be given DP placebo (3 tabs, given once a day for 3 consecutive days) every 4 weeks during pregnancy. During pregnancy, TS will be given to women at a dose of 960mg once daily. Receives: Drug: Monthly placebo + daily trimethoprim/sulfamethoxazole (TS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Placental Malaria
The primary outcome will be the prevalence of placental malaria based on placental histopathology and dichotomized into any evidence of placental infection (parasites or pigment) vs. no evidence of placental infection.
Measured: at delivery estimated to be within 10 to 30 weeks of study entry
Incidence of Malaria, Pregnant Women
The primary outcome will be the 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 following administration of first dose of study drug to delivery
Secondary outcomes (5)
Maternal Parasitemia at Delivery by Microscopy and LAMP
Proportion of women with parasitemia detected by microscopy or LAMP at delivery
Measured: At delivery
Placental Parasitemia (Number of Women With Placental Blood Samples Positive for Malaria by Microscopy or PCR)
Proportion of placental blood samples positive for malaria by microscopy or PCR
Measured: At delivery
Number of Monthly Routine Visits With Positive Blood Samples for Parasites
Proportion of monthly routine blood samples positive by LAMP for parasites
Measured: Following administration of first dose of study drug to delivery
Composite Adverse Birth Outcome (Proportion With Low Birth Weight (<2500 gm), Spontaneous Abortion (<28 Weeks), Stillbirth (Fetal Demise ≥28 Weeks), Congenital Anomaly, or Preterm Delivery (<37 Weeks)
Proportion with low birth weight (<2500 gm), spontaneous abortion (<28 weeks), stillbirth (fetal demise ≥28 weeks), congenital anomaly, or preterm delivery (<37 weeks)
Measured: At delivery
Number of Routine Visits Measured Every 8 Weeks During Pregnancy for Which the Participants Had Anemia
Anemia (hemoglobin less than 11g/dL) measured every 8 weeks during pregnancy
Measured: Following administration of first dose of study drugs to delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2014 (estimated)
- Study start9 Dec 2014
- Primary completion26 May 2016
- Study completion26 May 2016
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.
- 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
- 200 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)
- Responsible party
- Principal investigator, Diana Havlir, University of California, San Francisco
- Investigators
- Diane V Havlir, MD, Principal investigator, University of California, San FranciscoGrant Dorsey, MD, PhD, Principal investigator, University of California, San FranciscoMoses R Kamya, MBChB, MMed, PhD, Principal investigator, Makerere University; Infectious Diseases Research Collaboration
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02282293
- Sponsor's protocol ID
- PROMOTE-BC2
- Status last verified
- Feb 2019
- First submitted
- 30 Oct 2014
- Last updated
- 5 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kajubi R, Huang L, Jagannathan P, Chamankhah N, Were M, Ruel T, Koss CA, Kakuru A, Mwebaza N, Kamya M, Havlir D, Dorsey G, Rosenthal PJ, Aweeka FT. Antiretroviral Therapy With Efavirenz Accentuates Pregnancy-Associated Reduction of Dihydroartemisinin-Piperaquine Exposure During Malaria Chemoprevention. Clin Pharmacol Ther. 2017 Sep;102(3):520-528. doi: 10.1002/cpt.664. Epub 2017 May 30.
PubMed 28187497Sonoiki E, Nsanzabana C, Legac J, Sindhe KM, DeRisi J, Rosenthal PJ. Altered Plasmodium falciparum Sensitivity to the Antiretroviral Protease Inhibitor Lopinavir Associated with Polymorphisms in pfmdr1. Antimicrob Agents Chemother. 2016 Dec 27;61(1):e01949-16. doi: 10.1128/AAC.01949-16. Print 2017 Jan.
PubMed 27821443Natureeba P, Kakuru A, Muhindo M, Ochieng T, Ategeka J, Koss CA, Plenty A, Charlebois ED, Clark TD, Nzarubara B, Nakalembe M, Cohan D, Rizzuto G, Muehlenbachs A, Ruel T, Jagannathan P, Havlir DV, Kamya MR, Dorsey G. Intermittent Preventive Treatment With Dihydroartemisinin-Piperaquine for the Prevention of Malaria Among HIV-Infected Pregnant Women. J Infect Dis. 2017 Jul 1;216(1):29-35. doi: 10.1093/infdis/jix110.
PubMed 28329368Prahl M, Jagannathan P, McIntyre TI, Auma A, Wamala S, Nalubega M, Musinguzi K, Naluwu K, Sikyoma E, Budker R, Odorizzi P, Kakuru A, Havlir DV, Kamya MR, Dorsey G, Feeney ME. Sex Disparity in Cord Blood FoxP3+ CD4 T Regulatory Cells in Infants Exposed to Malaria In Utero. Open Forum Infect Dis. 2017 Feb 11;4(1):ofx022. doi: 10.1093/ofid/ofx022. eCollection 2017 Winter.
PubMed 28480292Odorizzi PM, Feeney ME. Impact of In Utero Exposure to Malaria on Fetal T Cell Immunity. Trends Mol Med. 2016 Oct;22(10):877-888. doi: 10.1016/j.molmed.2016.08.005. Epub 2016 Sep 7.
PubMed 27614925Prahl M, Jagannathan P, McIntyre TI, Auma A, Farrington L, Wamala S, Nalubega M, Musinguzi K, Naluwu K, Sikyoma E, Budker R, Vance H, Odorizzi P, Nayebare P, Ategeka J, Kakuru A, Havlir DV, Kamya MR, Dorsey G, Feeney ME. Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation. Malar J. 2016 Oct 7;15(1):497. doi: 10.1186/s12936-016-1545-6.
PubMed 27717402Roh ME, Shiboski S, Natureeba P, Kakuru A, Muhindo M, Ochieng T, Plenty A, Koss CA, Clark TD, Awori P, Nakalambe M, Cohan D, Jagannathan P, Gosling R, Havlir DV, Kamya MR, Dorsey G. Protective Effect of Indoor Residual Spraying of Insecticide on Preterm Birth Among Pregnant Women With HIV Infection in Uganda: A Secondary Data Analysis. J Infect Dis. 2017 Dec 19;216(12):1541-1549. doi: 10.1093/infdis/jix533.
PubMed 29029337Pons-Duran C, Wassenaar MJ, Yovo KE, Marin-Carballo C, Briand V, Gonzalez R. Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women. Cochrane Database Syst Rev. 2024 Sep 26;9(9):CD006689. doi: 10.1002/14651858.CD006689.pub3.
PubMed 39324693Hughes 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 33020153Wallender E, Zhang N, Conrad M, Kakuru A, Muhindo M, Tumwebaze P, Kajubi R, Mota D, Legac J, Jagannathan P, Havlir D, Kamya M, Dorsey G, Aweeka F, Rosenthal PJ, Savic RM. Modeling Prevention of Malaria and Selection of Drug Resistance with Different Dosing Schedules of Dihydroartemisinin-Piperaquine Preventive Therapy during Pregnancy in Uganda. Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01393-18. doi: 10.1128/AAC.01393-18. Print 2019 Feb.
PubMed 30530597Wallender E, Vucicevic K, Jagannathan P, Huang L, Natureeba P, Kakuru A, Muhindo M, Nakalembe M, Havlir D, Kamya M, Aweeka F, Dorsey G, Rosenthal PJ, Savic RM. Predicting Optimal Dihydroartemisinin-Piperaquine Regimens to Prevent Malaria During Pregnancy for Human Immunodeficiency Virus-Infected Women Receiving Efavirenz. J Infect Dis. 2018 Mar 5;217(6):964-972. doi: 10.1093/infdis/jix660.
PubMed 29272443
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing the Burden of Malaria in HIV-Infected Pregnant Women and Their HIV-Exposed Children (PROMOTE Birth Cohort 2)
- ClinicalTrials.gov ID
- NCT02282293
- Acronym / sponsor ID
- PROMOTE-BC2
- Conditions
- Malaria, Human Immunodeficiency Virus
- Keywords
- Chemoprevention, Malaria, Uganda, Dihydroartemisinin-piperaquine, Trimethoprim-sulfamethoxazole, Human Immunodeficiency Virus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 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)
- Study start
- 9 Dec 2014 (actual)
- Primary completion
- 26 May 2016 (actual)
- Study completion
- 26 May 2016 (actual)
- First posted
- 4 Nov 2014 (estimated)
- Results
- Posted 5 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double-blinded, randomized controlled trial of 200 HIV-infected pregnant women living in Tororo, Uganda, an area of high malaria transmission. HIV-infected pregnant women between 12 and 28 weeks gestation will be randomized to receive enhanced malaria chemoprevention with monthly dihydroartemisinin-piperaquine (DP) versus monthly DP placebo. Their HIV-exposed children will receive the same prevention regimen from 2 to 24 months of age to which the mothers were randomized. All women will receive daily trimethoprim-sulfamethoxazole (TS) throughout the study per Uganda Ministry of Health guidelines. Children will also receive daily TS from 6 weeks to 24 months of age. TS will be considered a study drug only in infants and children beginning 6 weeks after cessation of breastfeeding and upon exclusion of HIV infection. Women and their children will be followed for 36 months after delivery. In a subset of the study population, the investigators will conduct an intensive pharmacokinetic study that will evaluate pharmacokinetic exposure of DP and EFV. The investigators will also measure HIV-related outcomes among the women enrolled in the study. The investigators will test the hypothesis that for HIV-infected mothers and HIV-exposed infants, that enhanced versus standard malaria chemoprevention in HIV-infected pregnant women and their children will reduce the incidence of malaria among children from 0 to 24 months of age and improve the development of naturally acquired antimalarial immunity.
Detailed description
Pregnant women will be scheduled to be seen in the study clinic every 4 weeks during their pregnancy. Women will be seen at 1 week, 6 weeks, and 3 months postpartum and every 3 months thereafter. 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. Women will be provided all routine HIV care at the clinic according to Uganda MOH guidelines. All women will have ARVs and TS dispensed at the study clinic. Counseling on breastfeeding and infant feeding will be provided per Uganda MOH guidelines. HIV care and breastfeeding and infant feeding recommendations may be changed to reflect the most recent standard of care per MOH guidelines. 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. Children will have care for HIV-exposed children according to MOH guidelines, with the exception that TS will be continued until 2 years of life. 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. 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, study drugs will be administered at the time of each routine visit.
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 |
|---|---|---|
| Daily TS + Monthly DP pregnancy | Active comparator | Drug: Monthly dihydroartemisinin-piperaquine (DP) + daily trimethoprim/sulfamethoxazole (TS)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. During pregancy, TS will be given to women at a dose of 960mg once daily. |
| Daily TS + DP Placebo pregnancy | Placebo comparator | Drug: Monthly placebo + daily trimethoprim/sulfamethoxazole (TS)Women will be given DP placebo (3 tabs, given once a day for 3 consecutive days) every 4 weeks during pregnancy. During pregnancy, TS will be given to women at a dose of 960mg once daily. |
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)
- Intrauterine pregnancy confirmed by ultrasound
- Estimated gestational age between 12-28 weeks
- Confirmed to be HIV-infected by Uganda country standard rapid HIV test
- 16 years of age or older
- Residency within 30 km of the study clinic
Key exclusion criteria (10 listed)
- History of serious adverse event to TS or DP
- Refusal to take cART during pregnancy or as part of routine HIV care
- Active medical problem requiring inpatient evaluation at the time of screening
- Intention of moving more than 30 km from the study clinic
- Active WHO stage 4 condition not stable under treatment
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) + daily trimethoprim/sulfamethoxazole (TS)Also: Duo-Cotexin (Holley-Cotec) | Drug | Daily TS + Monthly DP pregnancy |
| Monthly placebo + daily trimethoprim/sulfamethoxazole (TS) | Drug | Daily TS + DP Placebo pregnancy |
Primary outcome
Number of Participants With Placental Malaria
Time frame: at delivery estimated to be within 10 to 30 weeks of study entry
The primary outcome will be the prevalence of placental malaria based on placental histopathology and dichotomized into any evidence of placental infection (parasites or pigment) vs. no evidence of placental infection.
Incidence of Malaria, Pregnant Women
Time frame: Time at risk will begin following administration of first dose of study drug to delivery
The primary outcome will be the 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.
5 secondary outcomes
Maternal Parasitemia at Delivery by Microscopy and LAMP
Time frame: At delivery
Placental Parasitemia (Number of Women With Placental Blood Samples Positive for Malaria by Microscopy or PCR)
Time frame: At delivery
Number of Monthly Routine Visits With Positive Blood Samples for Parasites
Time frame: Following administration of first dose of study drug to delivery
Composite Adverse Birth Outcome (Proportion With Low Birth Weight (<2500 gm), Spontaneous Abortion (<28 Weeks), Stillbirth (Fetal Demise ≥28 Weeks), Congenital Anomaly, or Preterm Delivery (<37 Weeks)
Time frame: At delivery
Number of Routine Visits Measured Every 8 Weeks During Pregnancy for Which the Participants Had Anemia
Time frame: Following administration of first dose of study drugs to delivery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28187497Kajubi R, Huang L, Jagannathan P, Chamankhah N, Were M, Ruel T, Koss CA, Kakuru A, Mwebaza N, Kamya M, Havlir D, Dorsey G, Rosenthal PJ, Aweeka FT. Antiretroviral Therapy With Efavirenz Accentuates Pregnancy-Associated Reduction of Dihydroartemisinin-Piperaquine Exposure During Malaria Chemoprevention. Clin Pharmacol Ther. 2017 Sep;102(3):520-528. doi: 10.1002/cpt.664. Epub 2017 May 30.
- Background: PubMed 27821443Sonoiki E, Nsanzabana C, Legac J, Sindhe KM, DeRisi J, Rosenthal PJ. Altered Plasmodium falciparum Sensitivity to the Antiretroviral Protease Inhibitor Lopinavir Associated with Polymorphisms in pfmdr1. Antimicrob Agents Chemother. 2016 Dec 27;61(1):e01949-16. doi: 10.1128/AAC.01949-16. Print 2017 Jan.
- Results publication: PubMed 28329368Natureeba P, Kakuru A, Muhindo M, Ochieng T, Ategeka J, Koss CA, Plenty A, Charlebois ED, Clark TD, Nzarubara B, Nakalembe M, Cohan D, Rizzuto G, Muehlenbachs A, Ruel T, Jagannathan P, Havlir DV, Kamya MR, Dorsey G. Intermittent Preventive Treatment With Dihydroartemisinin-Piperaquine for the Prevention of Malaria Among HIV-Infected Pregnant Women. J Infect Dis. 2017 Jul 1;216(1):29-35. doi: 10.1093/infdis/jix110.
- Results publication: PubMed 28480292Prahl M, Jagannathan P, McIntyre TI, Auma A, Wamala S, Nalubega M, Musinguzi K, Naluwu K, Sikyoma E, Budker R, Odorizzi P, Kakuru A, Havlir DV, Kamya MR, Dorsey G, Feeney ME. Sex Disparity in Cord Blood FoxP3+ CD4 T Regulatory Cells in Infants Exposed to Malaria In Utero. Open Forum Infect Dis. 2017 Feb 11;4(1):ofx022. doi: 10.1093/ofid/ofx022. eCollection 2017 Winter.
- Results publication: PubMed 27614925Odorizzi PM, Feeney ME. Impact of In Utero Exposure to Malaria on Fetal T Cell Immunity. Trends Mol Med. 2016 Oct;22(10):877-888. doi: 10.1016/j.molmed.2016.08.005. Epub 2016 Sep 7.
- Results publication: PubMed 27717402Prahl M, Jagannathan P, McIntyre TI, Auma A, Farrington L, Wamala S, Nalubega M, Musinguzi K, Naluwu K, Sikyoma E, Budker R, Vance H, Odorizzi P, Nayebare P, Ategeka J, Kakuru A, Havlir DV, Kamya MR, Dorsey G, Feeney ME. Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation. Malar J. 2016 Oct 7;15(1):497. doi: 10.1186/s12936-016-1545-6.
- Results publication: PubMed 29029337Roh ME, Shiboski S, Natureeba P, Kakuru A, Muhindo M, Ochieng T, Plenty A, Koss CA, Clark TD, Awori P, Nakalambe M, Cohan D, Jagannathan P, Gosling R, Havlir DV, Kamya MR, Dorsey G. Protective Effect of Indoor Residual Spraying of Insecticide on Preterm Birth Among Pregnant Women With HIV Infection in Uganda: A Secondary Data Analysis. J Infect Dis. 2017 Dec 19;216(12):1541-1549. doi: 10.1093/infdis/jix533.
- Derived from this study: PubMed 39324693Pons-Duran C, Wassenaar MJ, Yovo KE, Marin-Carballo C, Briand V, Gonzalez R. Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women. Cochrane Database Syst Rev. 2024 Sep 26;9(9):CD006689. doi: 10.1002/14651858.CD006689.pub3.
- 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 30530597Wallender E, Zhang N, Conrad M, Kakuru A, Muhindo M, Tumwebaze P, Kajubi R, Mota D, Legac J, Jagannathan P, Havlir D, Kamya M, Dorsey G, Aweeka F, Rosenthal PJ, Savic RM. Modeling Prevention of Malaria and Selection of Drug Resistance with Different Dosing Schedules of Dihydroartemisinin-Piperaquine Preventive Therapy during Pregnancy in Uganda. Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01393-18. doi: 10.1128/AAC.01393-18. Print 2019 Feb.
- Derived from this study: PubMed 29272443Wallender E, Vucicevic K, Jagannathan P, Huang L, Natureeba P, Kakuru A, Muhindo M, Nakalembe M, Havlir D, Kamya M, Aweeka F, Dorsey G, Rosenthal PJ, Savic RM. Predicting Optimal Dihydroartemisinin-Piperaquine Regimens to Prevent Malaria During Pregnancy for Human Immunodeficiency Virus-Infected Women Receiving Efavirenz. J Infect Dis. 2018 Mar 5;217(6):964-972. doi: 10.1093/infdis/jix660.
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
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.
Diane V Havlir, MD principal investigator
University of California, San Francisco
Grant Dorsey, MD, PhD principal investigator
University of California, San Francisco
Moses R 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?
A Phase 3 study testing Monthly dihydroartemisinin-piperaquine (DP) + daily trimethoprim/sulfamethoxazole (TS) in people with Malaria and Human Immunodeficiency Virus, 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 10 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 5 Mar 2019. 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. Some participants in this study may receive a placebo. 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 5 Mar 2019). 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 With Placental Malaria (time frame: at delivery estimated to be within 10 to 30 weeks of study entry). The study lists 2 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 NCT02282293, 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 5 Mar 2019.