Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women (PROMOTE-PIs)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00993031|
Recruitment Status : Completed
First Posted : October 9, 2009
Results First Posted : December 2, 2017
Last Update Posted : May 14, 2019
|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 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)
- 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 ]
- Number of Participants With Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group [ Time Frame: Time from randomization until one year follow up ]Proportion of women with severe maternal Anemia (hemoglobin < 8g/dl by hemacue or CBC) at any point during the trial in Each Treatment Group
- 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 from randomization until delivery ]Pre-eclampsia Defined by Hypertension > 140/90 on Two Occasions Measured > 6 Hours Apart With ≥1+ Proteinuria on Clean Catch Urine Dipstick
- Number of Participants With Maternal HIV RNA Suppression of <400 Copies/mL [ Time Frame: Time from randomization until delivery, an average of 20 weeks ]Virologic suppression was defined as plasma HIV-1 RNA 400 copies/ml or less based on the lower limit of detection of the available test.
- Change in Maternal CD4 Cell Counts [ Time Frame: Time of randomization to delivery, an average of 20 weeks ]CD4 cell count recovery efavirenz at delivery
- Number of Participants With Maternal to Child Transmission of HIV, Measured by Infant HIV DNA PCR [ Time Frame: Delivery to 48 weeks postpartum ]HIV tested by DNA PCR
- ART Levels in Hair Samples at Delivery [ Time Frame: delivery ]antiretroviral hair concentrations (per doubling)
- Number of Participants With Grade 3 or 4 Toxicity in the Two Treatment Groups in Women [ Time Frame: Randomization to one month postpartum ]
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|