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

NCT ID: NCT02819570

Last Updated: 2016-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2017-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Premature Rupture of Membrane

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

early-onset neonatal sepsis Prophylactic antibiotics Pregnancy PPROM EOS

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

Group Type EXPERIMENTAL

I.V cefuroxime 750 mg*3/d for 2 days

Intervention Type DRUG

P.O cefuroxime 500 mgx2/d for 5 days

Intervention Type DRUG

P.O roxithromycin 150 mg*2/d for 7 days

Intervention Type DRUG

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

Group Type ACTIVE_COMPARATOR

I.V ampicillin 2 gram x4/d for 2 days

Intervention Type DRUG

P.O roxithromycin 150 mg*2/d for 7 days

Intervention Type DRUG

P.O moxypen 500 mgx3/d for 5 days

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

I.V cefuroxime 750 mg*3/d for 2 days

Intervention Type DRUG

I.V ampicillin 2 gram x4/d for 2 days

Intervention Type DRUG

P.O cefuroxime 500 mgx2/d for 5 days

Intervention Type DRUG

P.O roxithromycin 150 mg*2/d for 7 days

Intervention Type DRUG

P.O moxypen 500 mgx3/d for 5 days

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Western Galilee Hospital-Nahariya

OTHER_GOV

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Dr. Maya Wolf

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Maya Wolf, MD

Role: PRINCIPAL_INVESTIGATOR

1Department of Obstetrics & Gynecology, Galilee Medical Center, 2Faculty of Medicine in the Galilee, Bar Ilan University, Nahariya, Israel

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Galil Medical Center

Nahariya, Israel, Israel

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Israel

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Maya Wolf, MD

Role: CONTACT

Phone: 972-507887800

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Maya Wolf, MD

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

Mercer BM. Preterm premature rupture of the membranes: current approaches to evaluation and management. Obstet Gynecol Clin North Am. 2005 Sep;32(3):411-28. doi: 10.1016/j.ogc.2005.03.003.

Reference Type BACKGROUND
PMID: 16125041 (View on PubMed)

Newton ER. Chorioamnionitis and intraamniotic infection. Clin Obstet Gynecol. 1993 Dec;36(4):795-808. doi: 10.1097/00003081-199312000-00004.

Reference Type BACKGROUND
PMID: 8293582 (View on PubMed)

Sperling RS, Newton E, Gibbs RS. Intraamniotic infection in low-birth-weight infants. J Infect Dis. 1988 Jan;157(1):113-7. doi: 10.1093/infdis/157.1.113.

Reference Type BACKGROUND
PMID: 3335795 (View on PubMed)

Practice bulletins No. 139: premature rupture of membranes. Obstet Gynecol. 2013 Oct;122(4):918-930. doi: 10.1097/01.AOG.0000435415.21944.8f.

Reference Type BACKGROUND
PMID: 24084566 (View on PubMed)

Carlan SJ, O'Brien WF, Parsons MT, Lense JJ. Preterm premature rupture of membranes: a randomized study of home versus hospital management. Obstet Gynecol. 1993 Jan;81(1):61-4.

Reference Type BACKGROUND
PMID: 8416463 (View on PubMed)

Turnbull DA, Wilkinson C, Gerard K, Shanahan M, Ryan P, Griffith EC, Kruzins G, Stamp GE. Clinical, psychosocial, and economic effects of antenatal day care for three medical complications of pregnancy: a randomised controlled trial of 395 women. Lancet. 2004 Apr 3;363(9415):1104-9. doi: 10.1016/S0140-6736(04)15893-5.

Reference Type BACKGROUND
PMID: 15064028 (View on PubMed)

Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD004454. doi: 10.1002/14651858.CD004454.pub2.

Reference Type BACKGROUND
PMID: 16856047 (View on PubMed)

Harding JE, Pang J, Knight DB, Liggins GC. Do antenatal corticosteroids help in the setting of preterm rupture of membranes? Am J Obstet Gynecol. 2001 Jan;184(2):131-9. doi: 10.1067/mob.2001.108331.

Reference Type BACKGROUND
PMID: 11174492 (View on PubMed)

Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev. 2013 Dec 2;2013(12):CD001058. doi: 10.1002/14651858.CD001058.pub3.

Reference Type BACKGROUND
PMID: 24297389 (View on PubMed)

Mercer BM, Miodovnik M, Thurnau GR, Goldenberg RL, Das AF, Ramsey RD, Rabello YA, Meis PJ, Moawad AH, Iams JD, Van Dorsten JP, Paul RH, Bottoms SF, Merenstein G, Thom EA, Roberts JM, McNellis D. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. JAMA. 1997 Sep 24;278(12):989-95.

Reference Type BACKGROUND
PMID: 9307346 (View on PubMed)

Workowski KA, Berman S; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17;59(RR-12):1-110.

Reference Type BACKGROUND
PMID: 21160459 (View on PubMed)

Grigsby PL, Novy MJ, Sadowsky DW, Morgan TK, Long M, Acosta E, Duffy LB, Waites KB. Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model. Am J Obstet Gynecol. 2012 Dec;207(6):475.e1-475.e14. doi: 10.1016/j.ajog.2012.10.871. Epub 2012 Oct 23.

Reference Type BACKGROUND
PMID: 23111115 (View on PubMed)

Wolf MF, Miron D, Peleg D, Rechnitzer H, Portnov I, Salim R, Keness Y, Reich D, Ami MB, Peretz A, Koshnir A, Shachar IB. Reconsidering the Current Preterm Premature Rupture of Membranes Antibiotic Prophylactic Protocol. Am J Perinatol. 2015 Nov;32(13):1247-50. doi: 10.1055/s-0035-1552935. Epub 2015 May 29.

Reference Type BACKGROUND
PMID: 26023907 (View on PubMed)

Sgayer I, Francis YN, Miron D, Shprits E, Sheffer VF, Rechnitzer H, Lowenstein L, Wolf MF. Compared perinatal outcomes of two prophylactic antibiotic regimens for preterm premature rupture of membranes: a randomized controlled trial. Am J Obstet Gynecol MFM. 2023 May;5(5):100900. doi: 10.1016/j.ajogmf.2023.100900. Epub 2023 Feb 13.

Reference Type DERIVED
PMID: 36791845 (View on PubMed)

Wolf MF, Sgayer I, Miron D, Krencel A, Sheffer VF, Idriss SS, Sammour RN, Peleg D, Shachar IB, Rechnitzer H, Bornstein J. A novel extended prophylactic antibiotic regimen in preterm pre-labor rupture of membranes: A randomized trial. Int J Infect Dis. 2020 Jul;96:254-259. doi: 10.1016/j.ijid.2020.05.005. Epub 2020 May 11.

Reference Type DERIVED
PMID: 32407901 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

0149-15-NHR

Identifier Type: -

Identifier Source: org_study_id