Evaluating Strategies to Reduce Mother-to-Child Transmission of HIV Infection in Populations Using Formula Feeding (PROMISE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01253538
First received: December 1, 2010
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to examine effective methods of preventing the transmission of HIV from mother to child during pregnancy, labor, and delivery. This is one part of the three-part PROMISE study. This study will be conducted at resource-limited locations in Africa and other parts of the world where women typically receive a short course of highly active antiretroviral therapy (HAART) during pregnancy and where formula feeding (FF) is standard.


Condition Intervention
HIV
Drug: Zidovudine (ZDV)
Drug: Nevirapine (NVP)
Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])
Drug: Lamivudine-Zidovudine (3TC-ZDV)
Drug: Lopinavir-ritonavir (LPV-RTV)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Formula Feeding Version of the PROMISE Study (Promoting Maternal and Infant Survival Everywhere)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Maternal Health Component: Composite endpoint of progression to AIDS-defining illness or death [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Antepartum Component: Confirmed presence of infant HIV infection [ Time Frame: Measured at birth or Week 1 ] [ Designated as safety issue: No ]
    Defined as HIV nucleic acid test (NAT) positivity of the specimen drawn at either the birth (Day 0-5) or Week 1 (Day 6-14) visit, confirmed by HIV NAT positivity of a second specimen collected at a different time point

  • Antepartum Component: Grade 3 or higher toxicity (for women, also selected Grade 2 hematologic, renal, and hepatic adverse events) [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Antepartum Component: Obstetrical complications [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Antepartum Component: Adverse pregnancy outcomes (e.g., stillbirth, preterm delivery at less than 37 weeks gestation, low birth weight less than 2,500 grams, and congenital anomalies) [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maternal Health Component: Death [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: AIDS-defining illness [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Composite endpoint of progression to AIDS-defining illness, death, or a serious non-AIDS cardiovascular, hepatic, or renal event [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: HIV/AIDS-related events [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Cardiovascular or other metabolic events [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Other targeted medical conditions [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Composite endpoint of HIV/AIDS-related event or death [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Composite endpoint of HIV/AIDS-related event or World Health Organization (WHO) Clinical Stage 2 or 3 event [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Composite endpoint of any condition outlined in Appendix IV of the protocol or death [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Tuberculosis [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Maternal Health Component: Toxicity, defined as Grade 3 or greater laboratory results or signs and symptoms and selected Grade 2 renal and hepatic laboratory results [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: Yes ]
  • Maternal Health Component: Viral resistance [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Maternal Health Component: Self-reported adherence [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Maternal Health Component: Quality of life [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Maternal Health Component: Changes in plasma concentrations of inflammatory and thrombogenic markers [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Maternal Health Component: Cost-effectiveness [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Antepartum Component: Infant HIV infection detected by HIV NAT positivity in the birth sample [ Time Frame: Measured at the end of the 5-year study period ] [ Designated as safety issue: No ]
  • Antepartum Component: Overall and HIV-free infant survival [ Time Frame: Measured through 24 months post-delivery ] [ Designated as safety issue: Yes ]
  • Antepartum Component: Adherence to the maternal ARV regimen, measured by maternal report [ Time Frame: Measured throughout study ] [ Designated as safety issue: No ]
  • Antepartum Component: Cost-effectiveness and feasibility of the trial ARV regimens [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
  • Antepartum Component: Maternal and infant viral resistance to the maternal and infant ARV strategies [ Time Frame: Measured throughout study ] [ Designated as safety issue: No ]
  • Antepartum Component: Antepartum change in HBV DNA viral load (using log HBV DNA) among women with detectable HBV DNA viral loads at baseline and other HBV outcome measures [ Time Frame: Measured at Week 8 ] [ Designated as safety issue: No ]
  • Antepartum Component: Maternal HIV RNA less than 400 copies/mL at delivery [ Time Frame: Measured at the time of delivery ] [ Designated as safety issue: No ]

Estimated Enrollment: 1000
Study Start Date: April 2011
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Antepartum: Arm A (Maternal Regimen)
Participants will receive ZDV + sdNVP + TRV.
Drug: Zidovudine (ZDV)
Antepartum Arm A: 300 mg orally twice daily beginning at greater than or equal to 14 weeks gestation (at study entry) through delivery
Other Names:
  • ZDV
  • AZT
  • Retrovir
Drug: Nevirapine (NVP)
For women, 200 mg orally (one single dose) at onset of labor; for infants with birth weight greater than or equal to 2,500 gm: 1.5 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or through the Week 6 study visit, whichever is later; for infants with a birth weight of 2,000 to 2, 499 gm: 1.0 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or until the Week 6 study visit, whichever is later; for infants with a birth weight of less than 2,000 gm: 2 mg/kg based on birth weight orally once a day beginning as soon as possible after birth through 3 weeks of age and 4 mg/kg based on weight at 3 weeks of age orally once a day beginning at 3 weeks of age through 42 days of age or through the Week 6 visit, whichever is later.
Other Name: NVP
Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])

Antepartum Arm A: 200 mg/300 mg x 2 tablets for a total dose of 400 mg/600 mg orally once ideally at onset of labor or as soon as possible thereafter; 200 mg/300 mg (1 tablet) orally each day after delivery for 7 days or the date of the Week 1 visit (up to 14 days), whichever is later.

Antepartum Arm C: 200 mg/300 mg orally once daily beginning at greater than or equal to 14 weeks gestation (at study entry) until Week 1 postpartum visit (up to 14 days)

Other Names:
  • TRV
  • FTC/TDF
Experimental: Antepartum: Arm B (Maternal Regimen)
Participants will receive 3TC-ZDV + LPV-RTV.
Drug: Lamivudine-Zidovudine (3TC-ZDV)
Antepartum Arm B: 150 mg/300 mg orally twice daily beginning at greater than or equal to 14 weeks gestation (at study entry) through delivery and until 1 week postpartum visit (up to 14 days)
Other Names:
  • 3TC-ZDV
  • Combivir
Drug: Lopinavir-ritonavir (LPV-RTV)

Antepartum Arm B: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days).

Antepartum Arm C: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).

Other Names:
  • LPV-RTV
  • LPV/r
  • Kaletra
Experimental: Antepartum: Arm C (Maternal Regimen)
Participants will receive TRV + LPV-RTV.
Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])

Antepartum Arm A: 200 mg/300 mg x 2 tablets for a total dose of 400 mg/600 mg orally once ideally at onset of labor or as soon as possible thereafter; 200 mg/300 mg (1 tablet) orally each day after delivery for 7 days or the date of the Week 1 visit (up to 14 days), whichever is later.

Antepartum Arm C: 200 mg/300 mg orally once daily beginning at greater than or equal to 14 weeks gestation (at study entry) until Week 1 postpartum visit (up to 14 days)

Other Names:
  • TRV
  • FTC/TDF
Drug: Lopinavir-ritonavir (LPV-RTV)

Antepartum Arm B: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days).

Antepartum Arm C: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).

Other Names:
  • LPV-RTV
  • LPV/r
  • Kaletra
Experimental: Infant Prophylaxis Regimen
All infants in the antepartum part of the study will receive NVP each day through 42 days of age or until the Week 6 study visit, whichever is later, regardless of the mother's study arm assignment.
Drug: Nevirapine (NVP)
For women, 200 mg orally (one single dose) at onset of labor; for infants with birth weight greater than or equal to 2,500 gm: 1.5 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or through the Week 6 study visit, whichever is later; for infants with a birth weight of 2,000 to 2, 499 gm: 1.0 mL suspension orally once a day beginning as soon as possible after birth through 42 days of age or until the Week 6 study visit, whichever is later; for infants with a birth weight of less than 2,000 gm: 2 mg/kg based on birth weight orally once a day beginning as soon as possible after birth through 3 weeks of age and 4 mg/kg based on weight at 3 weeks of age orally once a day beginning at 3 weeks of age through 42 days of age or through the Week 6 visit, whichever is later.
Other Name: NVP
Experimental: Maternal Health: Arm A (Continue triple ARV regimen)
Participants will continue receiving the triple ARV regimen (TRV + LPV-RTV).
Drug: Emtricitabine-tenofovir disoproxil fumarate (Truvada [TRV])

Antepartum Arm A: 200 mg/300 mg x 2 tablets for a total dose of 400 mg/600 mg orally once ideally at onset of labor or as soon as possible thereafter; 200 mg/300 mg (1 tablet) orally each day after delivery for 7 days or the date of the Week 1 visit (up to 14 days), whichever is later.

Antepartum Arm C: 200 mg/300 mg orally once daily beginning at greater than or equal to 14 weeks gestation (at study entry) until Week 1 postpartum visit (up to 14 days)

Other Names:
  • TRV
  • FTC/TDF
Drug: Lopinavir-ritonavir (LPV-RTV)

Antepartum Arm B: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at >/= 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning at >/= 28 weeks gestation or at next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until Week 1 postpartum visit (up to 14 days).

Antepartum Arm C: 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily beginning at > 14 weeks gestation (at study entry) through 28 weeks gestation (through second trimester); 200 mg/50 mg x 3 tablets for a dose of 600 mg/150 mg orally twice daily beginning > 28 weeks gestation, or at the next visit (during third trimester) through delivery; 200 mg/50 mg x 2 tablets for a dose of 400 mg/100 mg orally twice daily after delivery until week 1 postpartum visit (up to 14 days).

Other Names:
  • LPV-RTV
  • LPV/r
  • Kaletra
No Intervention: Maternal Health: Arm B (Discontinue triple ARV regimen)
Participants will discontinue the triple ARV regimen.

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Antepartum Component Inclusion Criteria (Step 1):

  • Confirmed HIV-1 infection, documented by the results of testing performed on two separate specimens at any time prior to study entry. More information on this criterion can be found in the protocol.
  • Currently pregnant and at greater than 14 weeks gestation based on clinical or other obstetrical measurements
  • CD4 count greater than or equal 350 cells/mm^3 or greater than or equal to the country-specific threshold for initiation of treatment, if that threshold is greater than 350 cells/mm^3 on a specimen obtained within 30 days prior to study entry
  • Results of HBV screening (hepatitis B surface antigen [HBsAg] testing) available from specimen obtained within 30 days prior to entry
  • Certain laboratory values from a specimen obtained within 30 days prior to study entry. More information on this criterion can be found in the protocol.
  • Plans to deliver in the study-affiliated clinic or hospital
  • Has no plans to move outside of the study site area during the 24 months following delivery
  • Age of legal majority for the respective country and willing and able to provide written informed consent
  • Intends to formula feed

Antepartum Component Exclusion Criteria (Step 1):

  • Participation in PROMISE for a prior pregnancy
  • Ingestion of any ARV regimen with three or more drugs (regardless of duration) or more than 30 days of a single or dual ARV regimen during current pregnancy, according to self report or available medical records
  • Requires triple-ARV therapy (HAART) for own health based on local standard guidelines
  • WHO Stage 4 disease
  • Prior receipt of HAART for maternal treatment indications (e.g., CD4 count less than 350 cells/mm^3 or clinical indications); however, could have received prior ARVs for the sole purpose of PMTCT in previous pregnancies; prior PMTCT regimens could have included a triple-ARV regimen, ZDV, 3TC-ZDV, and/or single-dose NVP for PMTCT as well as use of a short dual-nucleoside reverse transcriptase inhibitor (NRTI) "tail" to reduce risk of NVP resistance
  • In labor, onset or beyond
  • Clinically significant illness or condition requiring systemic treatment and/or hospitalization within 30 days prior to study entry
  • Current or history of tuberculosis (TB) disease (positive purified protein derivative [PPD] without TB disease is not exclusionary)
  • Use of prohibited medications within 14 days prior to study entry (refer to protocol for list of prohibited medications)
  • Fetus detected with serious congenital malformation (ultrasound not required to rule out this condition)
  • Current documented conduction heart defect (specialized assessments to rule out this condition are not required; a heart murmur alone and/or type 1 second-degree atrioventricular block (also known as Mobitz I or Wenckebach) is not considered exclusionary)
  • Known to meet the local standard criteria for treatment of HBV. More information on this criterion can be found in the protocol.
  • Social or other circumstances that would hinder long-term follow-up, in the opinion of the site investigator
  • Currently incarcerated

Antepartum Component Inclusion Criteria (Step 2):

  • On Antepartum Step 1 Arm A (ZDV + single dose NVP + TRV tail); OR
  • On Antepartum Step 1 Arm B or C (maternal triple-ARV prophylaxis) and currently receiving triple-ARV prophylaxis but does not meet the criteria for switching to a second line regimen (has not failed HAART) and Step 3 entry; OR
  • On Step 1 Arm B or C (maternal triple-ARV prophylaxis) and not enrolled in the Maternal Health Component but remains in observational follow-up and is not currently receiving a triple-ARV regimen (stopped the regimen)
  • Reached an indication for triple-ARV therapy (HAART) for own health, as specified in protocol
  • Willing and able to initiate HAART

Antepartum Component Exclusion Criteria (Step 2):

No exclusion criteria for this step.

Antepartum Component Inclusion Criteria (Step 3):

  • On Step 1 Arm B or C or on Step 2
  • Met the criteria for switching to a second-line regimen (as specified in the protocol) while on a triple-ARV regimen
  • Willing and able to continue a triple-ARV regimen

Antepartum Component Exclusion Criteria (Step 3):

- Women on 1077FA Step 1 Arm B or C who were not enrolled in the Maternal Health Component but remain in observational follow-up and are not currently receiving a triple-ARV regimen

Maternal Health Component Inclusion Criteria (Step 1):

  • Randomized to triple-ARV prophylaxis as part of the Antepartum Component and has continued triple-ARV prophylaxis until the current randomization (7 to 12 days postpartum) without treatment interruption (defined as more than 7 consecutive days of missed dosing) within the previous 30 days
  • Provided written informed consent
  • CD4 cell count greater than or equal to 350 cells/mm^3 or greater than or equal to the country-specific threshold for initiation of treatment, if that threshold is greater than 350 cells/mm^3, on specimen obtained within 30 days prior to study entry. More information on this criterion can be found in the protocol.
  • Certain laboratory values on a specimen obtained within 30 days prior to study entry. More information on this criterion can be found in the protocol.
  • Intend to remain in current geographical area of residence for the duration of study

Maternal Health Component Exclusion Criteria (Step 1):

  • WHO Stage 4 disease
  • Clinically significant illness or condition requiring systemic treatment and/or hospitalization within 30 days prior to entry in Maternal Health Component
  • Current or history of TB disease (positive PPD without TB disease is not exclusionary)
  • Use of prohibited medications within 14 days prior to entry in Maternal Health Component
  • Social or other circumstances that would hinder long-term follow-up, as judged by the site investigator
  • Current documented conduction heart defect (specialized assessments to rule out this condition are not required; a heart murmur alone and/or type 1 second-degree atrioventricular block (also known as Mobitz I or Wenckebach) is not considered exclusionary)
  • Requires triple-ARV therapy for own health (includes women who are on Step 2 of the Antepartum Component and women who are on Step 3 of the Antepartum Component who entered Step 3 for immunologic/clinical disease progression requiring a change in their triple-ARV regimen (HAART). More information on this criterion can be found in the protocol.

Maternal Health Component Inclusion Criteria (Step 2):

  • On Step 1 Arm B (discontinue the study triple-ARV regimen arm); OR
  • On Step 1 Arm A (triple-ARV regimen) and currently on the triple-ARV regimen but does not meet the criteria for switching to a second-line regimen and entry into Step 3
  • Reached an indication for triple-ARV treatment for her own health, as specified in the protocol
  • Willing and able to reinitiate or continue triple-ARV therapy

Maternal Health Component Exclusion Criteria (Step 2):

No exclusion criteria for this step.

Maternal Health Component Inclusion Criteria (Step 3):

  • On Step 1 Arm A or Step 2
  • Meets the criteria for switching to a second-line regimen as specified in protocol while on a triple-ARV regimen
  • Willing and able to continue an alternative triple-ARV regimen (HAART)

Maternal Health Component Exclusion Criteria (Step 3):

- On Step 1 Arm B

  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: NCT01253538

Locations
India
BJ Medical College CRS Recruiting
Pune, Maharashtra, India, 411001
Contact: Nishi Suryavanshi, Ph.D.    91-20-26052419    nishi@jhumitpune.com   
South Africa
Soweto IMPAACT CRS Recruiting
Johannesburg, Gauteng, South Africa, 2001
Contact: Nasreen Abrahams    27-11-9899742    abrahamsn@phru.co.za   
Shandukani Research CRS Withdrawn
Johannesburg, Gauteng, South Africa, 2001
Durban Paediatric HIV CRS Recruiting
Durban, KwaZulu-Natal, South Africa, 4001
Contact: Rosie Mngqibisa, MBBS    27-31-2604669    mngqibisa@ukzn.ac.za   
Stellenbosch Univ. CRS Recruiting
Cape Town, South Africa, 7505
Contact: Joan Coetzee    27-21-9384157    joan@sun.ac.za   
Sponsors and Collaborators
Investigators
Study Chair: Mary Glenn Fowler, MD, MPH Johns Hopkins Medical Institute
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01253538     History of Changes
Other Study ID Numbers: 1077FF (PROMISE), 10778, IMPAACT 1077 FF
Study First Received: December 1, 2010
Last Updated: December 2, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Mother-to-Child Transmission of HIV
HAART

Additional relevant MeSH terms:
Zidovudine
Nevirapine
Lamivudine
Tenofovir
Tenofovir disoproxil
Lamivudine, zidovudine drug combination
Ritonavir
Lopinavir
Emtricitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on July 10, 2014