Antibiotics and the Prolongation of Pregnancy in Preterm Labor With an Advanced Cervical Exam

This study has been terminated.
(published data suggest potential harm in other investigations.)
Sponsor:
Information provided by (Responsible Party):
Thaddeus Waters, MetroHealth Medical Center
ClinicalTrials.gov Identifier:
NCT00589329
First received: December 27, 2007
Last updated: October 23, 2012
Last verified: October 2012

December 27, 2007
October 23, 2012
December 2007
October 2012   (final data collection date for primary outcome measure)
Length of pregnancy prolongation [ Time Frame: Measured from randomization to delivery ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00589329 on ClinicalTrials.gov Archive Site
Respiratory distress [ Time Frame: newborn nursery ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Antibiotics and the Prolongation of Pregnancy in Preterm Labor With an Advanced Cervical Exam
Antibiotics and the Prolongation of Pregnancy in Preterm Labor With an Advanced Cervical Exam

Preterm birth, its causes, prevention, complications and ramifications persist as an important focus of obstetrical research. In the United States 11.8% of all live births occur prior to 37 weeks gestation. As many as 45% of these deliveries will have been proceeded by preterm labor with intact membranes.(2) Both preterm labor and preterm premature rupture of membranes have both been associated with evidence intrauterine infection. While antibiotic treatment in conservative management of preterm PROM remote from term has been shown to significantly prolong pregnancy and reduce infant morbidity, (16) data regarding the effectiveness of antibiotics for pregnancy prolongation in preterm labor are inconsistent. (3-15) Currently, narrow spectrum antibiotics (penicillin or clindamycin) are given prior to delivery to reduce the risk of neonatal Group B Beta Streptococcus (GBS) sepsis, however broad spectrum antibiotic treatment of women with preterm labor for pregnancy prolongation is not recommended.

Review of the literature regarding antibiotic treatment for pregnancy prolongation in preterm labor reveals that most studies utilized single agent therapy, and no study has evaluated the use of antibiotics for pregnancy prolongation in women with an advanced cervical exam (>4cm). While a number of studies have shown significant pregnancy prolongation in unselected populations,(5,12,13) only one study of 12 reviewed was able to show a neonatal benefit to adjunctive antibiotic use.(12,20) Norman, et al was able to show a reduction in the incidence of necrotising enterocolitis with the use of antibiotics. Given the number of studies in this area, and the lack of supporting evidence, this likely represents an alpha error. Another study by Svare et al was able to show a significant decrease in NICU admissions for women treated with antibiotics in the setting of preterm labor, however no change was reported in neonatal morbidities.

Our proposed study is designed to evaluate patients at particular risk for preterm delivery; those with advanced cervical exam. In this randomized prospective controlled study, we intend to examine the influence of adjunctive antibiotic use in preterm labor complicated by a cervical exam of 4 cm or greater. We plan to compare a study group receiving broad-spectrum antibiotics with a control group that will not receive antibiotics for pregnancy prolongation. Both groups will receive antibiotics for GBS prophylaxis as indicated. We hope to see a delay in delivery in the study group as a primary outcome. Secondary outcomes will include the use of steroids, neonatal complications including sepsis, intraventricular hemorrhage, periventricular leukomalacea, mechanical ventilation and respiratory distress syndrome, retinopathy of prematurity and necrotizing enterocolitis, and neonatal ICU stay.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Length of Pregnancy Prolongation in Hours
  • Drug: erythromycin and metronidazole (antibiotics)

    Erythromycin 250 mg IV q 6 hours x 8 doses, followed erythromycin 250 mg tabs, 1 PO q 8 hours for five days.

    Metronidazole, 1 gm IV loading dose followed by 500 mg IV q 12 hours x 4 doses, followed by metronidazole 500 mg tabs, 1 PO q 8 hours for five days

  • Drug: placebo
    IV and pill placebo
  • Experimental: A

    roup A will be assigned to receive antibiotics:

    • Erythromycin 250 mg IV q 6 hours x 8 doses, followed erythromycin 250 mg tabs, 1 PO q 8 hours for five days.
    • Metronidazole, 1 gm IV loading dose followed by 500 mg IV q 12 hours x 4 doses, followed by metronidazole 500 mg tabs, 1 PO q 8 hours for five days.
    Intervention: Drug: erythromycin and metronidazole (antibiotics)
  • Placebo Comparator: B
    Group B will not receive antibiotics for pregnancy prolongation, but will receive a matching masked placebo (IV saline and pill) regimen.
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
50
October 2012
October 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. All patients admitted with the diagnosis of preterm labor between 24 0/7 and 33 6/7 weeks gestation. Preterm labor will be defined by regular contractions and/or cervical change from last documented exam.
  2. Cervical exam 4 cm or greater
  3. Intact membranes

Exclusion Criteria:

  1. Multiple gestation (>2)
  2. Clinical evidence of chorioamnionitis, such as maternal fever, uterine tenderness, fetal tachycardia
  3. Lethal fetal anomaly
  4. Persistent vaginal bleeding, abruption, or placenta previa
  5. Rupture of membranes
  6. Maternal illness or fetal indication requiring delivery
  7. Inability to give informed consent
  8. Serious allergy to study medications. GI discomfort will not be considered a drug allergy
Female
18 Years to 40 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00589329
IRB01-00012
Yes
Thaddeus Waters, MetroHealth Medical Center
MetroHealth Medical Center
Not Provided
Principal Investigator: Brian Mercer, M.D. MetroHealth Medical Center MFM Director
Principal Investigator: Thaddeus Waters, M.D. MetroHealth Medical Center
MetroHealth Medical Center
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP