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Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes

Primary Purpose

Preterm Premature Rupture of Membrane

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Antibiotics
Sponsored by
Eastern Virginia Medical School
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Preterm Premature Rupture of Membrane

Eligibility Criteria

18 Years - 50 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Singleton pregnancy
  • PPROM from 22 weeks 0 days to 31 weeks 6 days at Sentara Norfolk General Hospital
  • Membrane rupture within 36 hours of randomization, cervical dilation 3 cm or less, and 4 or fewer contractions in the 60-minutes monitoring before randomization

Exclusion Criteria:

  • Non-reassuring fetal heart tracing
  • Vaginal bleeding
  • Indications for delivery
  • Received any antibiotic therapy within 7 days other than initiation of Ampicillin treatment as part of latency antibiotics prior to transfer to Sentara Norfolk General Hospital
  • Allergy to penicillin, erythromycin, or azithromycin

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Erythromycin

    Azithromycin

    Arm Description

    Receive 1) erythromycin 250 mg iv every 6 hours for 48 hours followed by 333 mg orally (pills) every 8 hours for 5 days

    Receive azithromycin 500 mg iv daily for 48 hours followed by 500 mg orally (pills) for 5 days.

    Outcomes

    Primary Outcome Measures

    Latency Period
    The time interval between the first antibiotic dose to time of delivery.

    Secondary Outcome Measures

    Full Information

    First Posted
    April 7, 2022
    Last Updated
    April 13, 2022
    Sponsor
    Eastern Virginia Medical School
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05328817
    Brief Title
    Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes
    Official Title
    Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes: A Randomized Controlled Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    May 1, 2022 (Anticipated)
    Primary Completion Date
    May 1, 2025 (Anticipated)
    Study Completion Date
    July 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Eastern Virginia Medical School

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Aim 1. To examine the latency period according to antibiotic regimens (erythromycin iv for two days followed by orally for 5 days vs. azithromycin iv for 2 days followed by 5 days orally). Aim 2. To examine the latency period according to races stratified by antibiotic regimens. Aim 3: To examine if there is a difference in neonatal morbidity and mortality stratified by antibiotic regimen.
    Detailed Description
    Significant differences exist in the pharmacokinetics and pharmacodynamics pathways of macrolide antibiotics between different races and ethnicities. Erythromycin compared to azithromycin interacts with more proteins and is likely affected by genetic variation. Therefore, the investigators hypothesize that the optimal latency antibiotic regimens for PPROM could potentially differ between races. Due to the paucity of data regarding the use of an azithromycin regimen for latency antibiotics, the Eastern Virginia Medical School MFM team uses an erythromycin regimen even though azithromycin requires less frequent dosing, has lower rates of side effects, and is more cost effective. The Center for Maternal and Child Health Equity at Eastern Virginia Medical School was developed to address health disparities for mothers and their children, and the investigator team is committed to working with the center to address this research gap regarding latency antibiotic use in PPROM. The aim is to determine the optimal antibiotic regimen for women with PPROM. The hypothesis to be tested are 1) The antibiotic regimen with azithromycin (iv for 2 days followed by 5 days orally) is associated with a longer latency period compared to the antibiotic regimen with erythromycin, and 2) The antibiotic regimen with azithromycin reduces disparity in latency period compared to the antibiotic regimen with erythromycin.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Preterm Premature Rupture of Membrane

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    In order to maintain balanced groups, block randomization will be used. Pregnant women will be randomized in blocks of 6 with a total number of blocks to be 40. This will be conducted using STATA16 software, which will generate random permutations of sequential IDs of eligible study participants and their assignment to the treatment arms. This will be transferred to the REDCap in which a database will be created to facilitate random assignment during recruitment while maintaining concealment of randomization.
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    240 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Erythromycin
    Arm Type
    Experimental
    Arm Description
    Receive 1) erythromycin 250 mg iv every 6 hours for 48 hours followed by 333 mg orally (pills) every 8 hours for 5 days
    Arm Title
    Azithromycin
    Arm Type
    Experimental
    Arm Description
    Receive azithromycin 500 mg iv daily for 48 hours followed by 500 mg orally (pills) for 5 days.
    Intervention Type
    Drug
    Intervention Name(s)
    Antibiotics
    Other Intervention Name(s)
    Latency antibiotics, Broad-spectrum antibiotics
    Intervention Description
    In the absence of labor, broad-spectrum antibiotics (often called latency antibiotics) are recommended for women with PPROM less than 34 weeks to reduce chorioamnionitis, prolong latency, and decrease neonatal sepsis (12,13).
    Primary Outcome Measure Information:
    Title
    Latency Period
    Description
    The time interval between the first antibiotic dose to time of delivery.
    Time Frame
    At delivery

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Singleton pregnancy PPROM from 22 weeks 0 days to 31 weeks 6 days at Sentara Norfolk General Hospital Membrane rupture within 36 hours of randomization, cervical dilation 3 cm or less, and 4 or fewer contractions in the 60-minutes monitoring before randomization Exclusion Criteria: Non-reassuring fetal heart tracing Vaginal bleeding Indications for delivery Received any antibiotic therapy within 7 days other than initiation of Ampicillin treatment as part of latency antibiotics prior to transfer to Sentara Norfolk General Hospital Allergy to penicillin, erythromycin, or azithromycin
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Tetsuya Kawakita, MD
    Phone
    757-446-7900
    Email
    kawakit@evms.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Kristin Ayers, MPH
    Phone
    7574460579
    Email
    ayerskl@evms.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Tetsuya Kawakita, MD
    Organizational Affiliation
    Eastern Virginia Medical School
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    21508700
    Citation
    Waters TP, Mercer B. Preterm PROM: prediction, prevention, principles. Clin Obstet Gynecol. 2011 Jun;54(2):307-12. doi: 10.1097/GRF.0b013e318217d4d3.
    Results Reference
    background
    PubMed Identifier
    3578431
    Citation
    Meis PJ, Ernest JM, Moore ML. Causes of low birth weight births in public and private patients. Am J Obstet Gynecol. 1987 May;156(5):1165-8. doi: 10.1016/0002-9378(87)90133-5.
    Results Reference
    background
    PubMed Identifier
    3752169
    Citation
    Beydoun SN, Yasin SY. Premature rupture of the membranes before 28 weeks: conservative management. Am J Obstet Gynecol. 1986 Sep;155(3):471-9. doi: 10.1016/0002-9378(86)90257-7.
    Results Reference
    background
    PubMed Identifier
    7070724
    Citation
    Garite TJ, Freeman RK. Chorioamnionitis in the preterm gestation. Obstet Gynecol. 1982 May;59(5):539-45.
    Results Reference
    background
    PubMed Identifier
    32109463
    Citation
    Pergialiotis V, Bellos I, Fanaki M, Antsaklis A, Loutradis D, Daskalakis G. The impact of residual oligohydramnios following preterm premature rupture of membranes on adverse pregnancy outcomes: a meta-analysis. Am J Obstet Gynecol. 2020 Jun;222(6):628-630. doi: 10.1016/j.ajog.2020.02.022. Epub 2020 Feb 25. No abstract available.
    Results Reference
    background
    PubMed Identifier
    23212881
    Citation
    Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ. 2012 Dec 4;345:e7976. doi: 10.1136/bmj.e7976.
    Results Reference
    background
    PubMed Identifier
    15635108
    Citation
    Marlow N, Wolke D, Bracewell MA, Samara M; EPICure Study Group. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med. 2005 Jan 6;352(1):9-19. doi: 10.1056/NEJMoa041367.
    Results Reference
    background
    PubMed Identifier
    7493703
    Citation
    Averbuch B, Mazor M, Shoham-Vardi I, Chaim W, Vardi H, Horowitz S, Shuster M. Intra-uterine infection in women with preterm premature rupture of membranes: maternal and neonatal characteristics. Eur J Obstet Gynecol Reprod Biol. 1995 Sep;62(1):25-9. doi: 10.1016/0301-2115(95)02176-8.
    Results Reference
    background
    PubMed Identifier
    18667175
    Citation
    Shen TT, DeFranco EA, Stamilio DM, Chang JJ, Muglia LJ. A population-based study of race-specific risk for preterm premature rupture of membranes. Am J Obstet Gynecol. 2008 Oct;199(4):373.e1-7. doi: 10.1016/j.ajog.2008.05.011. Epub 2008 Jul 29.
    Results Reference
    background
    PubMed Identifier
    27245741
    Citation
    Drassinower D, Friedman AM, Obican SG, Levin H, Gyamfi-Bannerman C. Prolonged latency of preterm prelabour rupture of membranes and neurodevelopmental outcomes: a secondary analysis. BJOG. 2016 Sep;123(10):1629-35. doi: 10.1111/1471-0528.14133. Epub 2016 May 31.
    Results Reference
    background
    PubMed Identifier
    31405887
    Citation
    Boghossian NS, Geraci M, Lorch SA, Phibbs CS, Edwards EM, Horbar JD. Racial and Ethnic Differences Over Time in Outcomes of Infants Born Less Than 30 Weeks' Gestation. Pediatrics. 2019 Sep;144(3):e20191106. doi: 10.1542/peds.2019-1106. Epub 2019 Aug 12.
    Results Reference
    background
    PubMed Identifier
    24297389
    Citation
    Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev. 2013 Dec 2;(12):CD001058. doi: 10.1002/14651858.CD001058.pub3.
    Results Reference
    background
    PubMed Identifier
    32080050
    Citation
    Prelabor Rupture of Membranes: ACOG Practice Bulletin, Number 217. Obstet Gynecol. 2020 Mar;135(3):e80-e97. doi: 10.1097/AOG.0000000000003700.
    Results Reference
    background
    PubMed Identifier
    1550145
    Citation
    Mercer BM, Moretti ML, Prevost RR, Sibai BM. Erythromycin therapy in preterm premature rupture of the membranes: a prospective, randomized trial of 220 patients. Am J Obstet Gynecol. 1992 Mar;166(3):794-802. doi: 10.1016/0002-9378(92)91336-9.
    Results Reference
    background
    PubMed Identifier
    9307346
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    18476121
    Citation
    Edwards MS, Newman RB, Carter SG, Leboeuf FW, Menard MK, Rainwater KP. Randomized Clinical Trial of Azithromycin vs. Erythromycin for the Treatment of Chlamydia Cervicitis in Pregnancy. Infect Dis Obstet Gynecol. 1996;4(6):333-7. doi: 10.1155/S1064744996000671.
    Results Reference
    background
    PubMed Identifier
    1656742
    Citation
    Hopkins S. Clinical toleration and safety of azithromycin. Am J Med. 1991 Sep 12;91(3A):40S-45S. doi: 10.1016/0002-9343(91)90401-i.
    Results Reference
    background
    PubMed Identifier
    30904320
    Citation
    Navathe R, Schoen CN, Heidari P, Bachilova S, Ward A, Tepper J, Visintainer P, Hoffman MK, Smith S, Berghella V, Roman A. Azithromycin vs erythromycin for the management of preterm premature rupture of membranes. Am J Obstet Gynecol. 2019 Aug;221(2):144.e1-144.e8. doi: 10.1016/j.ajog.2019.03.009. Epub 2019 Mar 20.
    Results Reference
    background
    PubMed Identifier
    28637060
    Citation
    Finneran MM, Appiagyei A, Templin M, Mertz H. Comparison of Azithromycin versus Erythromycin for Prolongation of Latency in Pregnancies Complicated by Preterm Premature Rupture of Membranes. Am J Perinatol. 2017 Sep;34(11):1102-1107. doi: 10.1055/s-0037-1603915. Epub 2017 Jun 21. No abstract available.
    Results Reference
    background
    PubMed Identifier
    25162251
    Citation
    Pierson RC, Gordon SS, Haas DM. A retrospective comparison of antibiotic regimens for preterm premature rupture of membranes. Obstet Gynecol. 2014 Sep;124(3):515-519. doi: 10.1097/AOG.0000000000000426.
    Results Reference
    background
    PubMed Identifier
    32694907
    Citation
    Martingano D, Singh S, Mitrofanova A. Azithromycin in the Treatment of Preterm Prelabor Rupture of Membranes Demonstrates a Lower Risk of Chorioamnionitis and Postpartum Endometritis with an Equivalent Latency Period Compared with Erythromycin Antibiotic Regimens. Infect Dis Obstet Gynecol. 2020 Jul 9;2020:2093530. doi: 10.1155/2020/2093530. eCollection 2020.
    Results Reference
    background
    PubMed Identifier
    25385446
    Citation
    Tsai D, Jamal JA, Davis JS, Lipman J, Roberts JA. Interethnic differences in pharmacokinetics of antibacterials. Clin Pharmacokinet. 2015 Mar;54(3):243-60. doi: 10.1007/s40262-014-0209-3.
    Results Reference
    background
    PubMed Identifier
    28146011
    Citation
    Fohner AE, Sparreboom A, Altman RB, Klein TE. PharmGKB summary: Macrolide antibiotic pathway, pharmacokinetics/pharmacodynamics. Pharmacogenet Genomics. 2017 Apr;27(4):164-167. doi: 10.1097/FPC.0000000000000270. No abstract available.
    Results Reference
    background
    PubMed Identifier
    27238715
    Citation
    Kumar D, Moore RM, Mercer BM, Mansour JM, Redline RW, Moore JJ. The physiology of fetal membrane weakening and rupture: Insights gained from the determination of physical properties revisited. Placenta. 2016 Jun;42:59-73. doi: 10.1016/j.placenta.2016.03.015. Epub 2016 Apr 1.
    Results Reference
    background

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    Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes

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