Comparison of Two Antibiotic Prophylactic Protocols in Preterm Premature Rupture of the Membranes

December 28, 2016 updated by: Dr. Maya Wolf, Western Galilee Hospital-Nahariya

Comparison of Two Antibiotic Prophylactic Protocols in Preterm Premature Rupture of the Membranes. A Randomized Prospective, Open Trial

The objective of the study is to compare a new antibiotic protocol with the current prophylactic treatment in routine use and to evaluate obstetric and neonatal outcome: preterm labor, chorioamnionitis and early onset sepsis

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Preterm premature rupture of membranes (PPROM) occurs in approximately 3% of all pregnancies and is associated with approximately one-third of preterm births. The incidence of chorioamnionitis in women with premature rupture of membranes (PROM) at < 27, 28 to 36, and > 37weeks' gestation is 41, 15, and 2%, respectively. Intra-amniotic infection is usually polymicrobial, comprised vaginal or enteric flora including aerobic and anaerobic bacteria and atypical agents, such as Mycoplasma. Group B streptococcus (GBS) has been a frequent pathogen. The American College of Obstetricians and Gynecologists approach to PPROM consists of recommending induction of labor in all women > 34 weeks' gestation. In the absence of intrauterine infection, placental abruption or non-reassuring fetal heart rate, management of women with PPROM < 34 weeks consists of hospitalization from the time of diagnosis until delivery, administration of antenatal corticosteroids, and a 7-day course of antibiotic prophylactic therapy to prolong the latency period. Antibiotic therapy has been associated with significant reductions in chorioamnionitis, deliveries within 48 hours, and early-onset (within 3 days of delivery) neonatal sepsis (EOS). The antibiotic regimen in PPROM usually consists of ampicillin intravenously for 48 hours, followed by oral amoxicillin for 5 days (specifically targeting GBS), and a macrolide targeting atypical agents.

An increase in EOS due to gram negative Enterobacteriaceae have been reported lately with a relative decrease in GBS related EOS . These data may have an impact on the antibiotic regimen used for PPROM. The Local pathogens distribution in cases of EOS and their antibiotic sensitivity profiles in Northern Israel have been explored in a multicenter study There were 27 neonates diagnosed with EOS with positive blood cultures. Aerobic Enterobacteriaceae accounted for 14 cases (52%) and group B streptococcus for 7 cases (26%). Of the Escherichia coli and Klebsiella sp.,only 38% were sensitive to ampicillin. As a result the most effective antibiotic protocol to cover those pathogens is required. The purpose of the current study is to compare a new antibiotic protocol with the current prophylactic treatment in use and to evaluate pregnancy and neonatal outcome.

The diagnosis of preterm premature rupture of membranes (PPROM) is clinical, and is based on visualization of amniotic fluid in the vagina of a woman who presents with a history of leaking fluid. Laboratory tests as "Amniosure" can be used to confirm the clinical diagnosis when it is uncertain.

Women who meet the study criteria and have signed inform consent will be randomly divided in two groups to receive prophylactic antibiotic treatment as follow:

  1. I.V ampicillin 2 gram x4/d for 2 days followed by P.O moxypen 500 mgx3/d for additional 5 days+ P.O roxithromycin 150 mg*2/d for 7 days
  2. I.V cefuroxime 750 mg*3/d for 2days followed by P.O cefuroxime 500 mgx2/d + P.O roxithromycin 150 mg*2/d for 7 days

A course of corticosteroids will be given to all women participating in the study

Expectant management:

  1. Vital signs *3/day
  2. Uterine tenderness evaluation
  3. Complete Blood Count + C-reactive protein every second day
  4. Urine culture and GBS recto-vaginal swab
  5. Fetal heart monitoring*6 /d
  6. Sonography evaluation every 2-3 days
  7. Vaginal swab once a week
  8. Fetal movements follow up

Labor induction will be conducted at 34 weeks of gestation If chorioamnionitis is suspected amniocentesis should be considered or expeditious delivery

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Nahariyya, Israel
        • Recruiting
        • Galil Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Women with PPROM between 24+0 and 34+0 weeks of gestation who are suitable for conservative management

Exclusion Criteria:

  • P-PROM>34 weeks of gestation
  • Suspected fetal distress or chorioamnionitis
  • Active labor
  • Drug allergy to one of the study regiments
  • Immune deficiency
  • Multiple pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: cefuroxime
I.V cefuroxime 750 mg*3/d for 2days followed by P.O cefuroxime 500 mgx2/d in addition to P.O roxithromycin 150 mg*2/d for 7 days
Drug: I.V cefuroxime 750 mg*3/d for 2 days
Drug: P.O cefuroxime 500 mgx2/d for 5 days
Drug: P.O roxithromycin 150 mg*2/d for 7 days
Active Comparator: ampicillin
I.V ampicillin 2 gram x4/d for 2 days followed by P.O moxypen 500 mgx3/d for 5 days in addition to P.O roxithromycin 150 mg*2/d for 7 days
Drug: P.O roxithromycin 150 mg*2/d for 7 days
Drug: I.V ampicillin 2 gram x4/d for 2 days
Drug: P.O moxypen 500 mgx3/d for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EARLY NEONATAL SEPSIS - positive blood culture
Time Frame: within 3 days of delivery
Number of Participants with early neonatal sepsis
within 3 days of delivery
latency period
Time Frame: from date of randomization until the date of delivery assessed up to 10 weeks
time in days
from date of randomization until the date of delivery assessed up to 10 weeks
Chorioamnionitis rate
Time Frame: from day of randomization until date of clinical/laboratory chorioamnionitis diagnosis assessed up to 10 weeks
rate of positive cultures
from day of randomization until date of clinical/laboratory chorioamnionitis diagnosis assessed up to 10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neonatal weight
Time Frame: at delivery
grams
at delivery
Apgar score
Time Frame: 1 minute 5 minute
score from 0 to 10
1 minute 5 minute

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events as assessed by umbilical cord acid-based analysis<7
Time Frame: at delivery
cord ph analysis at delivery (units of moles per liter)
at delivery
Neonatal intensive care unit (NICU) admission duration
Time Frame: days since delivery until rerelease from NICU, assessed up to 6 month
days from admission until rerelease from NICU assessed up to 6 month
days since delivery until rerelease from NICU, assessed up to 6 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Western Galilee Hospital-Nahariya

Investigators

  • Principal Investigator: Maya Wolf, MD, 1Department of Obstetrics & Gynecology, Galilee Medical Center, 2Faculty of Medicine in the Galilee, Bar Ilan University, Nahariya, Israel

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2015

Primary Completion (Anticipated)

December 1, 2017

Study Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

June 2, 2016

First Submitted That Met QC Criteria

June 29, 2016

First Posted (Estimate)

June 30, 2016

Study Record Updates

Last Update Posted (Estimate)

December 29, 2016

Last Update Submitted That Met QC Criteria

December 28, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0149-15-NHR

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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