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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

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

Condition or disease Intervention/treatment Phase
Premature Rupture of Membrane 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 Phase 4

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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


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Comparison of Two Antibiotic Prophylactic Protocols in Preterm Premature Rupture of the Membranes. A Randomized Prospective, Open Trial
Study Start Date : November 2015
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics Tears
Drug Information available for: Cefuroxime

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: 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



Primary Outcome Measures :
  1. EARLY NEONATAL SEPSIS - positive blood culture [ Time Frame: within 3 days of delivery ]
    Number of Participants with early neonatal sepsis

  2. latency period [ Time Frame: from date of randomization until the date of delivery assessed up to 10 weeks ]
    time in days

  3. Chorioamnionitis rate [ Time Frame: from day of randomization until date of clinical/laboratory chorioamnionitis diagnosis assessed up to 10 weeks ]
    rate of positive cultures


Secondary Outcome Measures :
  1. Neonatal weight [ Time Frame: at delivery ]
    grams

  2. Apgar score [ Time Frame: 1 minute 5 minute ]
    score from 0 to 10


Other Outcome Measures:
  1. 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)

  2. 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



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02819570


Contacts
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Contact: Maya Wolf, MD 972-507887800 homesickid@yahoo.com

Locations
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Israel
Galil Medical Center Recruiting
Nahariyya, Israel
Contact: Maya Wolf, MD    972-507887800    homesickid@yahoo.com   
Sponsors and Collaborators
Western Galilee Hospital-Nahariya
Investigators
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Principal Investigator: Maya Wolf, MD 1Department of Obstetrics & Gynecology, Galilee Medical Center, 2Faculty of Medicine in the Galilee, Bar Ilan University, Nahariya, Israel

Publications:

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Responsible Party: Dr. Maya Wolf, MD, Western Galilee Hospital-Nahariya
ClinicalTrials.gov Identifier: NCT02819570     History of Changes
Other Study ID Numbers: 0149-15-NHR
First Posted: June 30, 2016    Key Record Dates
Last Update Posted: December 29, 2016
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Dr. Maya Wolf, Western Galilee Hospital-Nahariya:
early-onset neonatal sepsis
Prophylactic antibiotics
Pregnancy
PPROM
EOS
Additional relevant MeSH terms:
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Ampicillin
Premature Birth
Fetal Membranes, Premature Rupture
Rupture
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Wounds and Injuries
Anti-Bacterial Agents
Cefuroxime
Cefuroxime axetil
Roxithromycin
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents