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

NCT ID: NCT00589329

Last Updated: 2019-09-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2012-10-31

Brief Summary

Preterm birth remains a major health concern affecting up to 12% of all live births prior to 37 weeks gestation. As preterm birth can often be associated with infection our proposal is to evaluate in a randomized fashion antibiotics for women with advanced cervical exams.

Detailed Description

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.

Conditions

Length of Pregnancy Prolongation in Hours

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

erythromycin and metronidazole (antibiotics)

Intervention Type: DRUG

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

B

Group B will not receive antibiotics for pregnancy prolongation, but will receive a matching masked placebo (IV saline and pill) regimen.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

IV and pill placebo

Interventions

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

Intervention Type: DRUG

placebo

IV and pill placebo

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

MetroHealth Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ted Waters

MFM attending, metroheatlh

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brian Mercer, M.D.

Role: PRINCIPAL_INVESTIGATOR

MetroHealth Medical Center MFM Director

Thaddeus Waters, M.D.

Role: PRINCIPAL_INVESTIGATOR

MetroHealth Medical Center

Locations

MetroHealth Medical Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

IRB01-00012

Identifier Type: -

Identifier Source: org_study_id