Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes

Preterm Premature Rupture of Membrane Clinical Trial

Official title:

Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes: A Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05328817
• Other study ID #: 22-01-FB-0001
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 1, 2022
• Est. completion date: July 1, 2025

Study information

• Verified date: April 2022
• Source: Eastern Virginia Medical School
• Contact: Tetsuya Kawakita, MD
• Phone: 757-446-7900
• Email: kawakit[@]evms.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 240
• Est. completion date: July 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Fetal Membranes, Premature Rupture
• Premature Birth
• Preterm Premature Rupture of Membrane
• Rupture

Intervention

Drug:
• Antibiotics
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).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Eastern Virginia Medical School

References & Publications (24)

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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). pii: e20191106. doi: 10.1542/peds.2019-1106. Epub 2019 Aug 12. — View Citation

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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. — View Citation

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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. — View Citation

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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. — View Citation

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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. — View 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. — View 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. — View 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. — View Citation

Prelabor Rupture of Membranes: ACOG Practice Bulletin, Number 217. Obstet Gynecol. 2020 Mar;135(3):e80-e97. doi: 10.1097/AOG.0000000000003700. — View 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. — View 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. Review. — View Citation

Waters TP, Mercer B. Preterm PROM: prediction, prevention, principles. Clin Obstet Gynecol. 2011 Jun;54(2):307-12. doi: 10.1097/GRF.0b013e318217d4d3. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Latency Period	The time interval between the first antibiotic dose to time of delivery.	At delivery