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Shortened Zidovudine Regimens to Prevent Mother-to-Child Transmission of HIV Type 1

Primary Purpose

HIV Infections, Pregnancy

Status
Completed
Phase
Phase 3
Locations
Thailand
Study Type
Interventional
Intervention
ZDV Short (mother)-Short (infant): Comparison of zidovudine durations
ZDV Short (mother)-Long (infant): Comparison of zidovudine durations
ZDV Long (mother)-Short (infant): Comparison of zidovudine durations
ZDV Long (mother)-Long (infant): Comparison of zidovudine durations
Sponsored by
Institut de Recherche pour le Developpement
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring transmission, infant, HIV, pregnancy, HIV-1 infection, HIV Seronegativity

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

Pre-inclusion

Women are eligible for Pre-Entry if they:

  • have evidence of HIV infection (confirmed on a second sample);
  • present themselves for prenatal care before 26 weeks GA, based on last menstrual period and/or sonogram results;
  • intend to stay in the province for at least 18 months after delivery;
  • can provide informed consent;
  • have given written informed consent to participate in the study;
  • intend to carry the pregnancy to term.

Inclusion Criteria:

  • all pre-entry criteria;
  • date of enrollment: 28 weeks GA, based on last menstrual period and/or sonogram results;
  • the following laboratory values within 21 days prior to randomization:
  • hemoglobin > 8.0 g/dL;
  • absolute neutrophil count > 750 cells/mm3;
  • SGPT < 5 x upper limit of normal;
  • serum creatinine < 1.5 mg/dL (women with a serum creatinine > 1.5 mg/dL must have a measured eight-hour urine creatinine clearance > 70 mL/min.);
  • agreement not to breastfeed.

Exclusion Criteria:

  • AIDS according to the Thai Communicable Diseases Control (CDC) classification;
  • pre-existing maternal/fetal condition that contraindicates the use of ZDV
  • oligohydramnios, unexplained polyhydramnios, fetal hydrops or ascites or other evidence of pre-existing in-utero anemia;
  • clinically significant history of intolerance to ZDV treatment resulting in discontinuation of therapy for more than 4 weeks;
  • receipt of ZDV during the current pregnancy for any indication, or women who need ZDV for their own health (women are then followed separately);
  • receipt of other antiretroviral agents, passive immunotherapy, anti-HIV vaccines, cytolytic agents (usually referred as chemotherapy), radiation therapy, or corticosteroids during this pregnancy except steroids less than 7 (see Zidovudine Investigator's Brochure);
  • simultaneous participation in another clinical trial.

Sites / Locations

  • Phpt - Ird 174

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

1

2

3

4

Arm Description

Maternal ZDV treatment starting at 35 weeks Gestational Age (GA) and continuing through labor and delivery, and three days of infant ZDV treatment starting at birth (Smother-Sinfant)

Maternal ZDV treatment starting at 35 weeks Gestational Age (GA) and continuing through labor and delivery, and six weeks of infant ZDV treatment starting at birth (Smother-Linfant)

Maternal ZDV treatment starting at 28 weeks Gestational Age (GA) and continuing through labor and delivery, and three days of infant ZDV treatment starting at birth (Lmother-Sinfant)

Maternal ZDV treatment starting at 28 weeks Gestational Age (GA) and continuing through labor and delivery, and six weeks of infant ZDV treatment starting at birth (Lmother-Linfant). This study arm was the reference regimen.

Outcomes

Primary Outcome Measures

Definitive HIV infection in children as assessed by positive PCR on two peripheral blood samples collected at two separate occasions.

Secondary Outcome Measures

Safety: clinical and biological assessment.

Full Information

First Posted
October 10, 2006
Last Updated
May 1, 2008
Sponsor
Institut de Recherche pour le Developpement
Collaborators
Harvard School of Public Health (HSPH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT00386230
Brief Title
Shortened Zidovudine Regimens to Prevent Mother-to-Child Transmission of HIV Type 1
Official Title
Short ZDV Course to Prevent Perinatal HIV in Thailand
Study Type
Interventional

2. Study Status

Record Verification Date
May 2008
Overall Recruitment Status
Completed
Study Start Date
June 1997 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 2000 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Institut de Recherche pour le Developpement
Collaborators
Harvard School of Public Health (HSPH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

5. Study Description

Brief Summary
The purpose of the study was to test the equivalence of a short zidovudine (ZDV) regimen as compared to a longer, ACTG-076-like, ZDV regimen in reducing the risk of mother-to-child transmission of HIV: and to assess and compare the safety and tolerance of the long and shortened ZDV regimens.
Detailed Description
Multicenter, randomized, four arms, double-blind, controlled study. Consenting pregnant women were tested for HIV from the beginning of pregnancy until 26 of gestational age (GA). If HIV-positive and eligible, women completed a Pre-entry baseline check-up. Enrollment took place at 28 weeks' gestational age. Women meeting selection criteria were randomly assigned to one of four study arms (see below). AMENDMENT (March 20, 1999) Data Safety and Monitory Board interim review (March 17, 1999) The DSMB reported that the transmission rate in the longest arm (long treatment of both mother and baby), was significantly lower than that in the shortest arm (short treatment of both the mother and the baby) and this discrepancy was larger than the previously agreed on difference which, if found, would call for changing the study design. In addition, the transmission rates in the remaining two arms of the study were similar to that in the longest arm. The difference that was found could not be explained by any baseline characteristics of the participants, such as maternal age, gestational age at delivery, birth weight, cesarean section rate, or any others. The DSMB recommended that enrollment into the shortest arm of the study be terminated, and the study be continued with a modification of design so that new enrollees would enter one of the three remaining arms. All women enrolled before this amendment was effective and delivering after March 20th, 1999, and previously randomized to the Smother-Sinfant arm, were unblinded in order to give their infants open label zidovudine for 6 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Pregnancy
Keywords
transmission, infant, HIV, pregnancy, HIV-1 infection, HIV Seronegativity

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
1554 (false)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Maternal ZDV treatment starting at 35 weeks Gestational Age (GA) and continuing through labor and delivery, and three days of infant ZDV treatment starting at birth (Smother-Sinfant)
Arm Title
2
Arm Type
Experimental
Arm Description
Maternal ZDV treatment starting at 35 weeks Gestational Age (GA) and continuing through labor and delivery, and six weeks of infant ZDV treatment starting at birth (Smother-Linfant)
Arm Title
3
Arm Type
Experimental
Arm Description
Maternal ZDV treatment starting at 28 weeks Gestational Age (GA) and continuing through labor and delivery, and three days of infant ZDV treatment starting at birth (Lmother-Sinfant)
Arm Title
4
Arm Type
Active Comparator
Arm Description
Maternal ZDV treatment starting at 28 weeks Gestational Age (GA) and continuing through labor and delivery, and six weeks of infant ZDV treatment starting at birth (Lmother-Linfant). This study arm was the reference regimen.
Intervention Type
Drug
Intervention Name(s)
ZDV Short (mother)-Short (infant): Comparison of zidovudine durations
Intervention Description
Maternal ZDV treatment (300 mg, twice daily) starting at 35 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Three days of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Smother-Sinfant)
Intervention Type
Drug
Intervention Name(s)
ZDV Short (mother)-Long (infant): Comparison of zidovudine durations
Intervention Description
Maternal ZDV treatment (300 mg, twice daily) starting at 35 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Six weeks of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Smother-Linfant)
Intervention Type
Drug
Intervention Name(s)
ZDV Long (mother)-Short (infant): Comparison of zidovudine durations
Intervention Description
Maternal ZDV treatment (300 mg, twice daily) starting at 28 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Three days of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Lmother-Sinfant)
Intervention Type
Drug
Intervention Name(s)
ZDV Long (mother)-Long (infant): Comparison of zidovudine durations
Intervention Description
Maternal ZDV treatment (300 mg, twice daily) starting at 28 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Six weeks of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Lmother-Linfant)
Primary Outcome Measure Information:
Title
Definitive HIV infection in children as assessed by positive PCR on two peripheral blood samples collected at two separate occasions.
Secondary Outcome Measure Information:
Title
Safety: clinical and biological assessment.

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
No
Eligibility Criteria
Pre-inclusion Women are eligible for Pre-Entry if they: have evidence of HIV infection (confirmed on a second sample); present themselves for prenatal care before 26 weeks GA, based on last menstrual period and/or sonogram results; intend to stay in the province for at least 18 months after delivery; can provide informed consent; have given written informed consent to participate in the study; intend to carry the pregnancy to term. Inclusion Criteria: all pre-entry criteria; date of enrollment: 28 weeks GA, based on last menstrual period and/or sonogram results; the following laboratory values within 21 days prior to randomization: hemoglobin > 8.0 g/dL; absolute neutrophil count > 750 cells/mm3; SGPT < 5 x upper limit of normal; serum creatinine < 1.5 mg/dL (women with a serum creatinine > 1.5 mg/dL must have a measured eight-hour urine creatinine clearance > 70 mL/min.); agreement not to breastfeed. Exclusion Criteria: AIDS according to the Thai Communicable Diseases Control (CDC) classification; pre-existing maternal/fetal condition that contraindicates the use of ZDV oligohydramnios, unexplained polyhydramnios, fetal hydrops or ascites or other evidence of pre-existing in-utero anemia; clinically significant history of intolerance to ZDV treatment resulting in discontinuation of therapy for more than 4 weeks; receipt of ZDV during the current pregnancy for any indication, or women who need ZDV for their own health (women are then followed separately); receipt of other antiretroviral agents, passive immunotherapy, anti-HIV vaccines, cytolytic agents (usually referred as chemotherapy), radiation therapy, or corticosteroids during this pregnancy except steroids less than 7 (see Zidovudine Investigator's Brochure); simultaneous participation in another clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Lallemant, MD
Organizational Affiliation
Institut de Recherche pour le Developpement
Official's Role
Principal Investigator
Facility Information:
Facility Name
Phpt - Ird 174
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand

12. IPD Sharing Statement

Citations:
PubMed Identifier
11018164
Citation
Lallemant M, Jourdain G, Le Coeur S, Kim S, Koetsawang S, Comeau AM, Phoolcharoen W, Essex M, McIntosh K, Vithayasai V. A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1. Perinatal HIV Prevention Trial (Thailand) Investigators. N Engl J Med. 2000 Oct 5;343(14):982-91. doi: 10.1056/NEJM200010053431401.
Results Reference
result
PubMed Identifier
25992639
Citation
Sripan P, Le Coeur S, Amzal B, Ingsrisawang L, Traisathit P, Ngo-Giang-Huong N, McIntosh K, Cressey TR, Sangsawang S, Rawangban B, Kanjanavikai P, Treluyer JM, Jourdain G, Lallemant M, Urien S. Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the Efficacy of Interventions for the Prevention of Perinatal HIV. PLoS One. 2015 May 19;10(5):e0126647. doi: 10.1371/journal.pone.0126647. eCollection 2015. Erratum In: PLoS One. 2015;10(6):e0130917. PLoS One. 2015;10(8):e0137368.
Results Reference
derived

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Shortened Zidovudine Regimens to Prevent Mother-to-Child Transmission of HIV Type 1

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