Antibiotics and the Prolongation of Pregnancy in Preterm Labor With an Advanced Cervical Exam - Full Text View

Purpose

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.

Condition	Intervention
Length of Pregnancy Prolongation in Hours	Drug: erythromycin and metronidazole (antibiotics) Drug: placebo


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Antibiotics and the Prolongation of Pregnancy in Preterm Labor With an Advanced Cervical Exam

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics

Drug Information available for: Erythromycin Metronidazole Erythromycin stearate Erythromycin ethylsuccinate Erythromycin phosphate Metronidazole hydrochloride

U.S. FDA Resources

Further study details as provided by MetroHealth Medical Center:

Primary Outcome Measures:

Length of pregnancy prolongation [ Time Frame: Measured from randomization to delivery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Respiratory distress [ Time Frame: newborn nursery ] [ Designated as safety issue: No ]


Enrollment:	50
Study Start Date:	December 2007
Study Completion Date:	October 2012
Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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
Placebo Comparator: B Group B will not receive antibiotics for pregnancy prolongation, but will receive a matching masked placebo (IV saline and pill) regimen.	Drug: placebo IV and pill placebo

Eligibility


Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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.
Cervical exam 4 cm or greater
Intact membranes

Exclusion Criteria:

Multiple gestation (>2)
Clinical evidence of chorioamnionitis, such as maternal fever, uterine tenderness, fetal tachycardia
Lethal fetal anomaly
Persistent vaginal bleeding, abruption, or placenta previa
Rupture of membranes
Maternal illness or fetal indication requiring delivery
Inability to give informed consent
Serious allergy to study medications. GI discomfort will not be considered a drug allergy

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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589329

Locations


United States, Ohio
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109

Sponsors and Collaborators

MetroHealth Medical Center

Investigators


Principal Investigator:	Brian Mercer, M.D.	MetroHealth Medical Center MFM Director
Principal Investigator:	Thaddeus Waters, M.D.	MetroHealth Medical Center

More Information

No publications provided


Responsible Party:	Thaddeus Waters, MFM attending, metroheatlh, MetroHealth Medical Center
ClinicalTrials.gov Identifier:	NCT00589329 History of Changes
Other Study ID Numbers:	IRB01-00012
Study First Received:	December 27, 2007
Last Updated:	October 23, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by MetroHealth Medical Center:


Preterm birth antibiotics preterm labor respiratory distress pergnancy

Additional relevant MeSH terms:


Anti-Bacterial Agents Antibiotics, Antitubercular Erythromycin Erythromycin Estolate Erythromycin Ethylsuccinate Erythromycin stearate Metronidazole Anti-Infective Agents Antiparasitic Agents	Antiprotozoal Agents Antitubercular Agents Enzyme Inhibitors Gastrointestinal Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Protein Synthesis Inhibitors Radiation-Sensitizing Agents Therapeutic Uses

ClinicalTrials.gov processed this record on March 01, 2015