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

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ClinicalTrials.gov Identifier: NCT02819570
Recruitment Status : Unknown
Verified December 2016 by Dr. Maya Wolf, Western Galilee Hospital-Nahariya.
Recruitment status was:  Recruiting
First Posted : June 30, 2016
Last Update Posted : December 29, 2016
Sponsor:
Information provided by (Responsible Party):
Dr. Maya Wolf, Western Galilee Hospital-Nahariya

Tracking Information
First Submitted Date  ICMJE June 2, 2016
First Posted Date  ICMJE June 30, 2016
Last Update Posted Date December 29, 2016
Study Start Date  ICMJE November 2015
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2016)
  • EARLY NEONATAL SEPSIS - positive blood culture [ Time Frame: within 3 days of delivery ]
    Number of Participants with early neonatal sepsis
  • latency period [ Time Frame: from date of randomization until the date of delivery assessed up to 10 weeks ]
    time in days
  • Chorioamnionitis rate [ Time Frame: from day of randomization until date of clinical/laboratory chorioamnionitis diagnosis assessed up to 10 weeks ]
    rate of positive cultures
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02819570 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2016)
  • Neonatal weight [ Time Frame: at delivery ]
    grams
  • Apgar score [ Time Frame: 1 minute 5 minute ]
    score from 0 to 10
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 29, 2016)
  • 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)
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Comparison of Two Antibiotic Prophylactic Protocols in Preterm Premature Rupture of the Membranes
Official Title  ICMJE Comparison of Two Antibiotic Prophylactic Protocols in Preterm Premature Rupture of the Membranes. A Randomized Prospective, Open Trial
Brief Summary 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
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Premature Rupture of Membrane
Intervention  ICMJE
  • Drug: I.V cefuroxime 750 mg*3/d for 2 days
  • Drug: I.V ampicillin 2 gram x4/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
  • Drug: P.O moxypen 500 mgx3/d for 5 days
Study Arms  ICMJE
  • 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
    Interventions:
    • 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
    Interventions:
    • Drug: I.V ampicillin 2 gram x4/d for 2 days
    • Drug: P.O roxithromycin 150 mg*2/d for 7 days
    • Drug: P.O moxypen 500 mgx3/d for 5 days
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 29, 2016)
400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2017
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02819570
Other Study ID Numbers  ICMJE 0149-15-NHR
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dr. Maya Wolf, Western Galilee Hospital-Nahariya
Study Sponsor  ICMJE Western Galilee Hospital-Nahariya
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Maya Wolf, MD 1Department of Obstetrics & Gynecology, Galilee Medical Center, 2Faculty of Medicine in the Galilee, Bar Ilan University, Nahariya, Israel
PRS Account Western Galilee Hospital-Nahariya
Verification Date December 2016

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