Antibiotics to Reduce Chorioamnionitis-Related Perinatal HIV Transmission

NCT ID: NCT00021671

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

3720 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2004-11-30

Brief Summary

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The purpose of this study is to see if antibiotic drugs given to treat an infection of the uterus during pregnancy can reduce the chances of HIV being passed from an HIV-positive mother to her baby.

A link between bacterial disease of the vagina, premature birth, infection of the uterus during pregnancy, and the passing of HIV from a mother to her baby has been found. Early treatment of these problems may reduce the risk of passing HIV from an HIV-positive mother to her baby.

\[Note: As of 02/21/03, enrollment into this study was halted because preliminary data showed that the study antibiotics were not effective in preventing mother-to-child HIV transmission.\]

Detailed Description

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Obstetric risk factors for HIV maternal-child transmission (MCT) include preterm birth, prolonged rupture of the membranes, and chorioamnionitis. Many preterm births are associated with and likely caused by chorioamnionitis. The relationship between bacterial vaginosis, preterm birth, histologic chorioamnionitis, and perinatal transmission of HIV has been consistently demonstrated. Perinatal HIV transmission is more common in preterm infants, and there is now evidence that subclinical chorioamnionitis is a substantial risk factor for MCT. For this study, the primary hypothesis is that early and appropriate treatment of subclinical chorioamnionitis prior to the onset of spontaneous preterm labor, and/or antibiotic treatment during labor, to prevent premature rupture of membrane-associated-chorioamnionitis, will reduce the risk of perinatal HIV transmission.

\[Note: As of 02/21/03, enrollment into this study was halted because preliminary data showed that the study antibiotics were not effective in preventing mother-to-child HIV transmission.\]

At 20 to 24 weeks, women who are randomized to receive antibiotics receive metronidazole and erythromycin for 7 days. Women randomized to the control group receive identically appearing placebos. With the onset of contractions and/or premature rupture of membranes, study participants will initiate a second oral course of antibiotics consisting of metronidazole and ampicillin or placebo every 4 hours, continuing after delivery until the course is completed. All HIV-infected women and their neonates will be offered the HIVNET 012 nevirapine (NVP) regimen. If the mother accepts the NVP for herself and her baby, she will be given 1 dose of NVP to be taken at onset of labor, and her baby will receive 1 dose of NVP at 72 hours post-birth or discharge, whichever occurs earlier. If the mother refuses NVP or is uninfected, she will receive a matched placebo at the 26- to 30-week visit to preserve participant confidentiality. This study takes place in Blantyre and Lilongwe, Malawi, in Lusaka, Zambia, and in Dar es Salaam, Tanzania.

Conditions

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HIV Infections

Keywords

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Drug Therapy, Combination Ampicillin Nevirapine Disease Transmission, Vertical Anti-Infective Agents Erythromycin Reverse Transcriptase Inhibitors Metronidazole Anti-HIV Agents Chorioamnionitis HIV Seronegativity

Study Design

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Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Interventions

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Erythromycin

Intervention Type DRUG

Nevirapine

Intervention Type DRUG

Ampicillin sodium

Intervention Type DRUG

Metronidazole

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV positive.
* 20 to 24 weeks pregnant.
* Willing to take the planned antibiotic treatment.
* Planning to deliver at 1 of the study sites.
* Willing to come back for follow-up visits for 1 year after the baby is born.

Exclusion Criteria

* Have taken antibiotics, except for syphilis or gonorrhea, within the last 2 weeks.
* Are allergic to penicillin, ampicillin, erythromycin, or metronidazole.
* Have major illnesses, such as diabetes, severe kidney or heart disease, or active tuberculosis, which might affect the pregnancy.
* Are having major problems with the pregnancy, such as placenta previa, ruptured membranes, or multiple pregnancy.
* Have a central nervous system disease, such as seizures.
* Are taking anticoagulant drugs.
Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Taha E Taha, MD, PhD

Role: STUDY_CHAIR

Johns Hopkins University

Robert Goldenberg, MD

Role: STUDY_CHAIR

Department of Obstetrics and Gynecology, University of Alabama at Birmingham

Locations

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Megan Valentine

Research Triangle Park, North Carolina, United States

Site Status

Countries

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United States

References

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Goldenberg RL, Andrews WW, Yuan AC, MacKay HT, St Louis ME. Sexually transmitted diseases and adverse outcomes of pregnancy. Clin Perinatol. 1997 Mar;24(1):23-41.

Reference Type BACKGROUND
PMID: 9099500 (View on PubMed)

St Louis ME, Kamenga M, Brown C, Nelson AM, Manzila T, Batter V, Behets F, Kabagabo U, Ryder RW, Oxtoby M, et al. Risk for perinatal HIV-1 transmission according to maternal immunologic, virologic, and placental factors. JAMA. 1993 Jun 9;269(22):2853-9.

Reference Type BACKGROUND
PMID: 8098783 (View on PubMed)

Hauth JC, Goldenberg RL, Andrews WW, DuBard MB, Copper RL. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. N Engl J Med. 1995 Dec 28;333(26):1732-6. doi: 10.1056/NEJM199512283332603.

Reference Type BACKGROUND
PMID: 7491136 (View on PubMed)

Mercer BM, Miodovnik M, Thurnau GR, Goldenberg RL, Das AF, Ramsey RD, Rabello YA, Meis PJ, Moawad AH, Iams JD, Van Dorsten JP, Paul RH, Bottoms SF, Merenstein G, Thom EA, Roberts JM, McNellis D. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. JAMA. 1997 Sep 24;278(12):989-95.

Reference Type BACKGROUND
PMID: 9307346 (View on PubMed)

Chi BH, Wang L, Read JS, Sheriff M, Fiscus S, Brown ER, Taha TE, Valentine M, Goldenberg R. Timing of maternal and neonatal dosing of nevirapine and the risk of mother-to-child transmission of HIV-1: HIVNET 024. AIDS. 2005 Nov 4;19(16):1857-64. doi: 10.1097/01.aids.0000189863.82429.2f.

Reference Type RESULT
PMID: 16227794 (View on PubMed)

Goldenberg RL, Mudenda V, Read JS, Brown ER, Sinkala M, Kamiza S, Martinson F, Kaaya E, Hoffman I, Fawzi W, Valentine M, Taha TE; HPTN 024 Study Team. HPTN 024 study: histologic chorioamnionitis, antibiotics and adverse infant outcomes in a predominantly HIV-1-infected African population. Am J Obstet Gynecol. 2006 Oct;195(4):1065-74. doi: 10.1016/j.ajog.2006.05.046. Epub 2006 Jul 26.

Reference Type RESULT
PMID: 16875654 (View on PubMed)

Goldenberg RL, Mwatha A, Read JS, Adeniyi-Jones S, Sinkala M, Msmanga G, Martinson F, Hoffman I, Fawzi W, Valentine M, Emel L, Brown E, Mudenda V, Taha TE; Hptn024 Team. The HPTN 024 Study: the efficacy of antibiotics to prevent chorioamnionitis and preterm birth. Am J Obstet Gynecol. 2006 Mar;194(3):650-61. doi: 10.1016/j.ajog.2006.01.004.

Reference Type RESULT
PMID: 16522393 (View on PubMed)

Mwinga K, Vermund SH, Chen YQ, Mwatha A, Read JS, Urassa W, Carpenetti N, Valentine M, Goldenberg RL. Selected hematologic and biochemical measurements in African HIV-infected and uninfected pregnant women and their infants: the HIV Prevention Trials Network 024 protocol. BMC Pediatr. 2009 Aug 7;9:49. doi: 10.1186/1471-2431-9-49.

Reference Type DERIVED
PMID: 19664210 (View on PubMed)

Chi BH, Wang L, Read JS, Taha TE, Sinkala M, Brown ER, Valentine M, Martinson F, Goldenberg RL. Predictors of stillbirth in sub-saharan Africa. Obstet Gynecol. 2007 Nov;110(5):989-97. doi: 10.1097/01.AOG.0000281667.35113.a5.

Reference Type DERIVED
PMID: 17978109 (View on PubMed)

Goldenberg RL, Andrews WW, Hoffman I, Fawzi W, Valentine M, Young A, Read JS, Brown ER, Mudenda V, Kafulafula G, Mwinga K, Taha TE. Fetal fibronectin and adverse infant outcomes in a predominantly human immunodeficiency virus-infected African population: a randomized controlled trial. Obstet Gynecol. 2007 Feb;109(2 Pt 1):392-401. doi: 10.1097/01.AOG.0000247628.68415.00.

Reference Type DERIVED
PMID: 17267841 (View on PubMed)

Other Identifiers

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11622

Identifier Type: REGISTRY

Identifier Source: secondary_id

HIVNET 024

Identifier Type: -

Identifier Source: org_study_id