Efficacy of Nevirapine Compared to ZDV + 3TC Administered in Labor and Again at Postdelivery in HIV Positive Women

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02181933
First received: July 2, 2014
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

The primary objective of the study was to evaluate the efficacy of nevirapine versus ZDV+3TC (Zidovudine + Lamivudine), when administered in labor and again at postdelivery, in reducing peripartum mother to child transmission of HIV (Human Immunodeficiency Virus).

The secondary objective was to assess the overall HIV transmission rate between the 2 groups (intrauterine, intrapartum and postpartum up to 6 weeks) as well as to explore the relationship between infection and timing of maternal dose relative to birth, infant feeding method, maternal peripheral blood viral load, and other potential risk factors for transmission.

Following the introduction of the second and third Amendments to the Protocol, 2 substudies were added. The objectives of these substudies were to evaluate the frequency of resistance-conferring mutations to nevirapine (Amendment 2) and to ZDV+3TC (Amendment 3); to determine whether there was a reversion of any resistant virus to the wild type; and to determine if the resistant virus was transmitted from the mother to the child.


Condition Intervention Phase
HIV Infections
Drug: Nevirapine
Drug: Zidovudine (ZDV)
Drug: Lamivudine (3TC)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Randomised Open Label Clinical Trial to Determine the Efficacy of Nevirapine, Compared With a Combination of ZDV + 3TC, in Decreasing the Peripartum Mother to Child Transmission of HIV. Women, Who Present After 38 Weeks Gestation or in Labour After 35 Weeks Gestation and Who Are Anti-retroviral Naive, Will be Included.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Incidence of HIV transmission from a HIV positive mother to her exposed infant during the intrapartum and early postpartum period [ Time Frame: Day 28, 42 and 56-84 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall HIV transmission rate (including intrauterine, intrapartum and postpartum) [ Time Frame: up to 84 days ] [ Designated as safety issue: No ]
  • Time to infection [ Time Frame: up to 84 days ] [ Designated as safety issue: No ]
  • Relationship between infection and timing of maternal dose relative to birth [ Time Frame: up to 84 days ] [ Designated as safety issue: No ]
  • Relationship between infection and infant feeding method [ Time Frame: up to 84 days ] [ Designated as safety issue: No ]
  • Relationship between infection and maternal peripheral blood viral load [ Time Frame: Day 0 and 28 ] [ Designated as safety issue: No ]
  • Relationship between infection and other potential risk factors [ Time Frame: up to 84 days ] [ Designated as safety issue: No ]
  • Number of patients with adverse events [ Time Frame: up to 84 days ] [ Designated as safety issue: No ]

Enrollment: 2648
Study Start Date: April 1999
Primary Completion Date: January 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nevirapine
Mother: two doses, Infant: one dose
Drug: Nevirapine
Active Comparator: Zidovudine (ZDV) + Lamivudine (3TC) Drug: Zidovudine (ZDV) Drug: Lamivudine (3TC)

  Eligibility

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

Inclusion Criteria:

  • Pregnant women who present after 38 weeks gestation or in labour after 35 weeks gestation who are tested HIV positive. Estimated gestational age will be determined by one or more of the following:

    • Reliable menstrual history, which corresponds with uterine size
    • Physical examination
    • Estimated fetal weight
  • A consent form for the mother and neonate will be signed by either the mother or the guardian prior to inclusion

Exclusion Criteria:

  • Mothers who have taken any antiretrovirals in the last 12 months
  • Mothers who are not able to take oral medication
  • Mothers who present with ARDS (acute respiratory distress syndrome), septic shock or eclampsia
  • Mothers presenting in discomfort, i.e. regular painful uterine contractions, or other factors that may contribute to her not being able to understand and sign the informed consent for HIV testing and study participation
  • Use of another investigational drug or concurrent participation in another investigational protocol during the current pregnancy
  • Unwillingness or inability to reasonably comply with the protocol (i.e., mother and neonate/infant could not be followed for the full 6 weeks of the trial)
  • Grade 4 SGPT (Serum glutamate pyruvate transaminase) (>10 times the upper limit of normal value), if known prior to delivery
  • A recent history (6 months preceding the study) or current evidence of drug abuse and/or alcoholism
  • Mothers with fetuses with anomalies incompatible with life, if known prior to delivery
  • Decision to deliver the infant by elective Cesarean section
  • Amniocentesis was indicated
  • Infants with severe growth retardation diagnosed before birth

Infants who fall into the following groups will not receive treatment, but the mother-infant pair will remain in the trial

  • Infants with malformations incompatible with life
  • Life-threatening perinatal conditions which do not allow oral therapy (e.g., sepsis)
  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.

No Contacts or Locations Provided
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02181933     History of Changes
Other Study ID Numbers: 1100.1287
Study First Received: July 2, 2014
Last Updated: July 11, 2014
Health Authority: South Africa: Department of Health

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
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
Lamivudine
Zidovudine
Nevirapine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
Antimetabolites

ClinicalTrials.gov processed this record on October 01, 2014