Trial record 8 of 8 for:    nichd Preeclampsia/Eclampsia

Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women (PROMOTE-PIs)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Diana Havlir, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00993031
First received: October 8, 2009
Last updated: October 15, 2013
Last verified: October 2013
  Purpose

This study is an open-label, single site, randomized controlled trial comparing protease inhibitor (PI)-based antiretroviral therapy (ART) to non-PI based ART for HIV-infected pregnant and breastfeeding women of all CD4 cell counts at high risk of malaria. The study is designed to test the hypothesis that pregnant women receiving a PI-based ART regimen will have lower risk of placental malaria compared to pregnant women receiving a non-PI based ART regimen. The primary study endpoint of the study is placental malaria. This study also enrolls the infants of these women at the time of delivery.


Condition Intervention Phase
Malaria
HIV Infections
Drug: Lopinavir/ritonavir
Drug: Efavirenz
Drug: Zidovudine
Drug: Lamivudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Prevalence of malaria defined as positive placental blood smear or positive placental blood PCR [ Time Frame: Delivery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Placental malaria defined as positive placental histopathology or positive rapid diagnostic test [ Time Frame: Delivery ] [ Designated as safety issue: No ]
  • Maternal malaria defined as the number of treatments for new episodes of malaria per time at risk [ Time Frame: Time from randomization until 24 months after delivery or cessation of breastfeeding ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in maternal CD4 cell counts and % CD4 [ Time Frame: From ART initiation to delivery and from delivery to the cessation of breastfeeding ] [ Designated as safety issue: No ]
  • Development of one or more new maternal HIV antiretroviral resistance mutations [ Time Frame: Measured at delivery and 24 weeks postpartum. ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 391
Study Start Date: December 2009
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg
Drug: Lopinavir/ritonavir
LPV 200mg/r 50mg
Other Names:
  • Kaletra
  • Aluvia
Drug: Zidovudine
Zidovudine 300 mg
Drug: Lamivudine
Lamivudine 150 mg
Active Comparator: Group B
ZDV 300mg/3TC 150mg/EFV 600mg
Drug: Efavirenz
600mg
Drug: Zidovudine
Zidovudine 300 mg
Drug: Lamivudine
Lamivudine 150 mg

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 16 years (if <18 years old, living independently from parents)
  2. Documentation of HIV status must come from two assays. Assays include DNA PCR, HIV RNA, Western blot, or rapid HIV antibody test
  3. Confirmed pregnancy by positive serum or urine pregnancy test or ultrasound
  4. Estimated gestational age between 12 and 28 weeks (based on first day of last menstrual period with physical exam confirmation and ultrasound confirmation) at time of enrollment
  5. Residency within 30 km of the study site
  6. Willing to provide informed consent

Exclusion Criteria:

  1. Current or prior use of HAART
  2. Exposure to single-dose NVP (alone or with zidovudine or zidovudine/lamivudine or other abbreviated monotherapy or dual therapy for PMTCT) less than 24 months prior to enrollment
  3. Prior dose-limited toxicity to TS within 14 days of study enrollment
  4. Receipt of any contraindicated medications within 14 days of study enrollment (See Appendix III.)
  5. Active tuberculosis or other WHO Stage 4 diseases
  6. Screening laboratory values:

    1. Hemoglobin: <7.5 g/dL (Note: Women found to have a hemoglobin <7.5 at screening may receive iron and folic acid and/or a blood transfusion at the physician's discretion. If a repeat hemoglobin is ≥7.5 g/dL, the woman may be considered for study inclusion.)
    2. Absolute neutrophil count (ANC): <750/mm3
    3. Platelet count: <50,000/mm3
    4. ALT: >225 U/L (>5.0x ULN)
    5. AST: >225 U/L (>5.0x ULN)
    6. Bilirubin (total): > 2.5x ULN
    7. Creatinine: > 1.8x ULN
  7. Known cardiac conduction abnormalities or structural heart defect

NOTE: A woman will be excluded from study participation during the current pregnancy if she goes into labor, experiences ruptured membranes or develops active tuberculosis or a WHO stage 4 condition following study enrollment but prior to study drug initiation.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00993031

Locations
Uganda
Tororo District Hospital
Tororo, Uganda
Sponsors and Collaborators
University of California, San Francisco
Investigators
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
  More Information

Additional Information:
Publications:

Responsible Party: Diana Havlir, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00993031     History of Changes
Other Study ID Numbers: H5741-34342, PO1HD059454, 2009-141, HS-670, 592/ESR/NDA/DID-09/2009, H5741-34342 and 10-02958
Study First Received: October 8, 2009
Last Updated: October 15, 2013
Health Authority: United States: Food and Drug Administration
Uganda: National Drug Authority
Uganda: National Council for Science and Technology

Keywords provided by University of California, San Francisco:
HIV
Placental Malaria
Pregnancy
Uganda
Protease inhibitors
Trimethoprim-sulfamethoxazole
Treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Malaria
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protozoan Infections
Parasitic Diseases
Protease Inhibitors
Ritonavir
Lopinavir
HIV Protease Inhibitors
Efavirenz
Trimethoprim-Sulfamethoxazole Combination
Zidovudine
Lamivudine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014