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

• Sponsor: MetroHealth Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00589329
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 58
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Length of Pregnancy Prolongation in Hours	Drug: erythromycin and metronidazole (antibiotics); Drug: placebo	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Antibiotics and the Prolongation of Pregnancy in Preterm Labor With an Advanced Cervical Exam
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Length of Pregnancy Prolongation [Measured from randomization to delivery in hours]

   The length of time (in hours) from initiation of therapy to delivery will establish the latency

Secondary Outcome Measures

1. Respiratory Distress [newborn nursery]

   Respiratory distress will be defined by the clinical record documentation of the neonatal team.

Eligibility Criteria

Criteria

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ted Waters, MFM attending, metroheatlh, MetroHealth Medical Center
• ClinicalTrials.gov Identifier: NCT00589329
• Other Study ID Numbers: IRB01-00012
• First Posted: Jan 9, 2008
• Last Update Posted: Sep 4, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Ted Waters, MFM attending, metroheatlh, MetroHealth Medical Center: Preterm birth; antibiotics; preterm labor; respiratory distress; pergnancy
• Additional relevant MeSH terms: Obstetric Labor, Premature; Anti-Bacterial Agents; Metronidazole; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin stearate

Study Results

Participant Flow

Arm/Group Title	Group A	Group B
Arm/Group Description	Group 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. 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	Group B will not receive antibiotics for pregnancy prolongation, but will receive a matching masked placebo (IV saline and pill) regimen. placebo: IV and pill placebo
Period Title: Overall Study
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Group A	Group B	Total
Arm/Group Description	Antibiotic group	Non antibiotic group	Total of all reporting groups
Overall Participants	10	10	20
Age, Customized (Count of Participants)
Count of Participants [Participants]	10 100%	10 100%	20 100%
Sex: Female, Male (Count of Participants)
Female	10 100%	10 100%	20 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Length of Pregnancy Prolongation
Description	The length of time (in hours) from initiation of therapy to delivery will establish the latency
Time Frame	Measured from randomization to delivery in hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B
Arm/Group Description	Group 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. 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	Group B will not receive antibiotics for pregnancy prolongation, but will receive a matching masked placebo (IV saline and pill) regimen. placebo: IV and pill placebo
Measure Participants	10	10
Mean (Full Range) [hours]	4	4

2. Secondary Outcome

Title	Respiratory Distress
Description	Respiratory distress will be defined by the clinical record documentation of the neonatal team.
Time Frame	newborn nursery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B
Arm/Group Description	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. 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	Group B will not receive antibiotics for pregnancy prolongation, but will receive a matching masked placebo (IV saline and pill) regimen. placebo: IV and pill placebo
Measure Participants	10	10
Count of Participants [Participants]	2 20%	1 10%

Adverse Events

Arm/Group Title	Group A		Group B
Arm/Group Description	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. 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		Group B will not receive antibiotics for pregnancy prolongation, but will receive a matching masked placebo (IV saline and pill) regimen. placebo: IV and pill placebo
All Cause Mortality
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.