Clinical trial NCT00386230: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Pregnancy
Keywords: transmission
infant
HIV
pregnancy
HIV-1 infection
HIV Seronegativity
Lead sponsor: Institut de Recherche pour le Developpement
Sponsor class: OTHER_GOV
Collaborators: name: Harvard School of Public Health (HSPH)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2006-10-11
Enrollment: 1554
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Definitive HIV infection in children as assessed by positive PCR on two peripheral blood samples collected at two separate occasions.
Secondary outcomes:
measure: Safety: clinical and biological assessment.
Other outcomes:
Locations:
city: Chiang Mai
country: Thailand
facility: Phpt - Ird 174
Study officials:
affiliation: Institut de Recherche pour le Developpement
name: Marc Lallemant, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.