Overview

This trial is active, not recruiting.

Conditions malaria, human immunodeficiency virus
Treatments monthly dihydroartemisinin-piperaquine (dp) for adult women during pregnancy, monthly dihydroartemisinin-piperaquine (dp) for infants, placebo
Phase phase 3
Sponsor University of California, San Francisco
Collaborator Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Start date December 2014
End date August 2018
Trial size 200 participants
Trial identifier NCT02282293, PROMOTE-BC2

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 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(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. Infants will be given DP (half strength tablets once a day for 3 consecutive days) every four weeks from 2 months to 24 months of age. Infants will be given TS daily starting at 6 weeks of life using weight-based guidelines.
monthly dihydroartemisinin-piperaquine (dp) for adult women during pregnancy Duo-Cotexin (Holley-Cotec)
monthly dihydroartemisinin-piperaquine (dp) for infants Duo-Cotexin (Holley-Cotec)
(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. Infants will be given DP placebo (tablets once a day for 3 consecutive days) every four weeks from 2 months to 24 months of age. Infants will be given TS daily starting at 6 weeks of life using weight-based guidelines.
placebo

Primary Outcomes

Measure
Prevalence of placental malaria
time frame: at delivery estimated to be within 10 to 30 weeks of study entry
Incidence of malaria, pregnant women
time frame: Time at risk will begin at birth and will end when study participants reaches 24 months of age, when the intervention will be stopped, or early study termination (if prior to 24 months of age).
Incidence of malaria, infants during the first 24 months of life
time frame: Time at risk will begin at birth and will end at 24 months of life
Virologic suppression in pregnant women
time frame: at delivery estimated to be within 10 to 30 weeks of study entry
Incidence of malaria, infants during 24 - 36 months of life
time frame: 24 - 36 months of life

Secondary Outcomes

Measure
Placental malaria (Proportion of placentas with histopathologic evidence of malaria)
time frame: at delivery estimated to be within 10 to 30 weeks of study entry
Placental parasitemia (Proportion of placental blood samples positive for malaria by microscopy or PCR)
time frame: at delivery estimated to be within 10 to 30 weeks of study entry
Maternal clinical malaria during pregnancy (Incidence of malaria while on malaria chemoprevention)
time frame: Gestational Age between 12-28 weeks (at study entry) up to delivery
Clinical malaria in children after stopping DP or DP placebo
time frame: From age 24 months to age 36 months.
Prevalence of asymptomatic parasitemia
time frame: Women: Gestational age between 12-28 weeks (at study entry) up to delivery; Infants: Birth up to 24 months of age or early
Incidence of adverse events in pregnant women and infants
time frame: For women, starting at the time of their first study drugs approximately gestational age between 12-28 weeks up to one month post-deliver; For infants: from birth up to up to 108 weeks of age
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 estimated to be within 10 to 30 weeks of study entry
HIV virologic suppression
time frame: Gestational age between 12 and 28 weeks to 3 years postpartum
HIV-free survival in children
time frame: 36 months old
WHO HIV conditions (WHO stage 3 and 4 conditions)
time frame: Women: Gestational age between 12-20 weeks (at study entry) up to delivery; Infants: Birth up to 24 months of age or early study termination
ARV adherence and exposure (72 hour pill recall, ARV levels in paired hair and blood samples)
time frame: Gestational age between 12-20 weeks (at study entry) up to delivery

Eligibility Criteria

Female participants at least 16 years old.

Inclusion Criteria: 1. Intrauterine pregnancy confirmed by ultrasound 2. Estimated gestational age between 12-28 weeks 3. Confirmed to be HIV-infected by Uganda country standard rapid HIV test 4. 16 years of age or older 5. Residency within 30 km of the study clinic 6. Provision of informed consent 7. Agreement to come to the study clinic for any febrile episode or other illness and avoid medications given outside the study protocol 8. Plan to deliver in the hospital Exclusion Criteria: 1. History of serious adverse event to TS or DP 2. Refusal to take cART during pregnancy or as part of routine HIV care 3. Active medical problem requiring inpatient evaluation at the time of screening 4. Intention of moving more than 30 km from the study clinic 5. Active WHO stage 4 condition not stable under treatment 6. Signs or symptoms of early or active labor 7. Currently on ritonavir 8. Currently taking drugs associated with known risk of Torsades de pointes 9. Currently taking CYP3A inhibitor medications which potentially inhibit the metabolism of piperaquine 10. History of cardiac problems or fainting

Additional Information

Official title Reducing the Burden of Malaria in HIV-Infected Pregnant Women and Their HIV-Exposed Children (PROMOTE Birth Cohort 2)
Principal investigator Diane V Havlir, MD
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 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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2015.
Information provided to ClinicalTrials.gov by University of California, San Francisco.