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
About this trial
This is an interventional treatment trial for Preterm Premature Rupture of Membrane
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
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
NCT ID
NCT05328817
First Posted
April 7, 2022
Last Updated
April 13, 2022
Sponsor
Eastern Virginia Medical School
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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