Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women (PROMOTE-PIs)
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|ClinicalTrials.gov Identifier: NCT00993031|
Recruitment Status : Completed
First Posted : October 9, 2009
Results First Posted : December 2, 2017
Last Update Posted : December 2, 2017
|Condition or disease||Intervention/treatment||Phase|
|Malaria HIV Infections||Drug: Lopinavir/ritonavir Drug: Efavirenz Drug: Zidovudine Drug: Lamivudine||Phase 3|
The study site will be the Tororo district hospital campus situated in Eastern Uganda, an area of high malaria transmission. Using convenience sampling, we will enroll 500 HIV-infected pregnant women and their infants from the Tororo community. Eligible women between 12-28 weeks gestation will be randomized at enrollment to receive either a PI- based or an NNRTI-based ART regimen after stratification by gravidity (G1 versus G2+) and gestational age (<24 weeks versus ≥ 24 weeks at enrollment).
Treatment group A will receive Zidovudine 300mg + Lamivudine 150mg + Lopinavir/ritonavir 200mg/50mg. Treatment group B will receive Zidovudine 300mg + Lamivudine 150mg + Efavirenz 600mg.
At enrollment, all study participants will receive a long lasting ITN and, as available, a basic care package including a safe water vessel, multivitamins and condoms, as per current standard of care for HIV-infected pregnant women in Uganda, if they have not already received these interventions from the referral site. Two ITNs will be provided for each mother-infant pair. Participants will receive all routine and acute medical care at a designated study clinic open 7 days a week from 8 a.m. to 5 p.m. If medical care is needed after hours, participants will be instructed to come to Tororo District Hospital premises (where the study clinic is located) and request that the study physician on-call be contacted. They will be followed up from the time of enrollment during pregnancy and through the cessation of breastfeeding; seen monthly for routine assessments and laboratory evaluations. Following delivery, the infants of enrolled women will be followed until 6 weeks following the cessation of breastfeeding but not beyond 58 weeks of life. Study participants will be followed closely for adverse events potentially due to study drugs and for malaria and HIV treatment outcomes. During the follow-up period, all patients presenting to the clinic with a new episode of fever will undergo standard evaluation (history, physical examination and Giemsa-stained blood smear) for the diagnosis of malaria.
Women will receive the study treatment from the time of study entry and randomization (12-28 weeks gestation) until 1 week following the cessation of breastfeeding (but no longer than 1 year + 1 week postpartum). If a subject experiences a toxicity endpoint, ART will be changed to provide antiviral activity prior to delivery. Exclusive breastfeeding will be encouraged until 24 weeks postpartum which is the standard of care in Uganda. As per updated WHO guidelines, women will be encouraged to introduce food at 6 months of life and continue breastfeeding until 1 year of life. Women will be counseled to wean over the course of 1 month and continue antiretrovirals for at least 1 week following weaning. Furthermore, if an infant is found to be HIV-infected, Uganda MOH and WHO guidelines recommend the continuation of breastfeeding until 2 years of life and daily TS. All women will receive daily oral trimethoprim/sulfamethoxazole (TS) per Ugandan MOH guidelines.
Per Ugandan MOH guidelines, all newborns will receive nevirapine syrup (10mg/ml) starting within 12 hours after birth for 6 weeks, daily oral TS from 6 weeks of life until 6 weeks following the cessation of breastfeeding, and their mothers will be instructed on ITN use for their infants.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||389 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women|
|Actual Study Start Date :||December 15, 2009|
|Actual Primary Completion Date :||July 2013|
|Actual Study Completion Date :||July 2013|
Experimental: Group A
ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg
LPV 200mg/r 50mg
Zidovudine 300 mg
Lamivudine 150 mg
Active Comparator: Group B
ZDV 300mg/3TC 150mg/EFV 600mg
Zidovudine 300 mg
Lamivudine 150 mg
- Prevalence of Malaria Defined as Positive Placental Blood Smear [ Time Frame: Delivery ]Number of participants with positive placental blood smear for malaria
- Prevalence of Malaria Defined as Positive Placental Blood PCR [ Time Frame: Delivery ]Number of participants with positive placental blood PCR for malaria
- Placental Malaria Defined as Positive Placental RDT [ Time Frame: Delivery ]Number of participants with positive placental RDT for malaria. Malaria rapid diagnostic tests (RDTs) assist in the diagnosis of malaria by detecting evidence of malaria parasites (antigens) in human blood. RDTs permit a reliable detection of malaria infections particularly in remote areas with limited access to good quality microscopy services.
- Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk During Pregnancy [ Time Frame: Number of treatments given for clinical malaria based on postive blood smear from time from randomization until 24 months after delivery or cessation of breastfeeding ]
- Prevalence of Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group [ Time Frame: Time from randomization until 24 months postpartum or cessation of breastfeeding ]number of evaluated participants with severe maternal anemia defined by hemoglobin < 8g/dl at any point during the trial in each treatment group
- Prevalence of Composite Clinical Outcome Defined by LBW, Stillbirth(Intrauterine Fetal Demise >20wks GA), Late Spontaneous Abortion(Miscarriage 12-20wks GA), Preterm Delivery(<37wks Gestation), Neonatal Death(Death of Liveborn Infant Within First 28days) [ Time Frame: Time from randomization until 24 months postpartum or cessation of breastfeeding ]Percent of evaluated participants with composite clinical outcome defined by LBW, stillbirth (intrauterine fetal demise >20wks GA), late spontaneous abortion(miscarriage 12-20wks GA), preterm delivery(<37wks gestation), neonatal death(death of live-born infant within first 28 days)
- Incidence of Pre-eclampsia Defined by Hypertension > 140/90 on Two Occasions Measured > 6 Hours Apart With ≥1+ Proteinuria on Clean Catch Urine Dipstick [ Time Frame: Time of randomization until 4 weeks postpartum ]
- Maternal HIV RNA Suppression of <400 Copies/mL and of <50 Copies/mL [ Time Frame: At delivery and 24 weeks after the start of the treatment regimen ]
- Change in Maternal CD4 Cell Counts and % CD4 [ Time Frame: From ART initiation to delivery and from delivery to the cessation of breastfeeding ]
- Development of One or More New Maternal HIV Antiretroviral Resistance Mutations [ Time Frame: Measured at delivery and 24 weeks postpartum. ]
- Incidence of Maternal to Child Transmission of HIV, Measured by Infant HIV DNA PCR [ Time Frame: From delivery to 24 weeks of life or the cessation of breastfeeding if that occurs prior to 24 weeks of life ]
- ART Levels in Plasma and Hair Samples [ Time Frame: Women at 30-34 weeks gestation and 12 weeks postpartum; Infants at delivery, 12 weeks and 24 weeks of life. ]
- Prevalence of Grade 3 or 4 Toxicity at Any Point During the Trial in the Two Treatment Groups in Women and in Infants [ Time Frame: Time from randomization until 24 months postpartum or cessation of breastfeeding ]
- Placental Malaria Defined Placental Histopathologic Analysis [ Time Frame: Delivery ]Number of participants with positive placental histopathology slide for malaria
- Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk After Pregnancy [ Time Frame: Number of treatments given for clinical malaria based on postive blood smear from time from delivery until 24 months after delivery or cessation of breastfeeding ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00993031
|Tororo District Hospital|
|Principal Investigator:||Diane Havlir, MD||University of California, San Francisco|
|Study Chair:||Deborah Cohan, MD, MPH||University of California, San Francisco|
|Principal Investigator:||Moses R Kamya, MBChB, MMed, PhD||Makerere University|
|Study Chair:||Pius Okong, MMed, PhD||Ugandan Ministry of Health|
|Principal Investigator:||Grant Dorsey, MD, PhD||University of California, San Francisco|