Erythromycin Versus Azithromycin for Preterm Prelabor Rupture of Membranes

Premature Rupture of Membrane Clinical Trial

— PRACET  

Official title:

Erythromycin Versus Azithromycin for Preterm Prelabor Rupture of Membranes: A Cluster Randomized Comparative Effectiveness Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06273891
• Other study ID #: INOVA-2023-58
• Status: Recruiting
• Phase: Phase 3
• Start date: March 8, 2024
• Est. completion date: October 1, 2025

Study information

• Verified date: March 2024
• Source: Inova Fairfax Hospital
• Contact: Antonio Saad, MD, MBA
• Phone: 7037766040
• Email: antonio.saad[@]inova.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to help identify the best antibiotic treatment for pregnant people when their water breaks prematurely (a condition abbreviated as PPROM). Current practice is to attempt to maintain the pregnancy until at least 34 weeks gestational age, when the risks of prematurity to the baby are lessened. Research shows that antibiotics help the pregnancy last longer, but there have been limited studies about which combination works best. Currently, both azithromycin and erythromycin are accepted antibiotic treatments, in addition to ampicillin and amoxicillin. Participants diagnosed with PPROM will be randomized to receive ampicillin and amoxicillin plus either azithromycin or erythromycin, in addition to the care they would normally receive. Studying these two drugs will help decide the best care for future patients with PPROM.

Description:

Preterm pre-labor rupture of membranes (PPROM) complicates 3% of pregnancies and accounts for one-fourth to one-third of preterm births. PPROM is associated with significant maternal and neonatal morbidities, including chorioamnionitis, endometritis, neonatal sepsis, prematurity-related pathologies. In the absence of labor or indication for immediate delivery, patients who present at less than 34 weeks gestational age are treated with antibiotics to prolong pregnancy until 34 weeks when the risks of prematurity are decreased. Based on randomized trials, both the American College of Obstetrics and Gynecology (ACOG) and the Society of Maternal Fetal Medicine (SMFM) recommend IV ampicillin and IV erythromycin for 2 days, followed by an oral regimen of amoxicillin and erythromycin for 5 days. Due to the recent limited availability of erythromycin, azithromycin has been used a substitute. There have been observational studies showing no difference in duration of pregnancy between azithromycin and erythromycin, however no randomized controlled trial has been carried out to our knowledge. This study performs a cluster randomized controlled trial to examine the efficacy of azithromycin versus erythromycin as a component of the "latency antibiotics" used to prolong pregnancy in PPROM patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: October 1, 2025
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Pregnancy at 22 weeks 0 days to 32 weeks 6 days of gestation.
• Rupture of membranes confirmed by biochemical testing.
• Membrane rupture within the past 36 hours.
• Cervical dilation 3 cm or less and 4 or fewer contractions within 60-minutes at the time of admission.
• Age =18 and <50 years.

Exclusion Criteria:

• Non-reassuring fetal heart tracing, vaginal bleeding, chorioamnionitis or any indication for delivery at admission.
• Allergy to penicillin, erythromycin, or azithromycin.
• Multiple gestations.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Erythromycin
Erythromycin 250 mg IV every 6 hours for 48 hours, followed by 250 mg PO or 333 mg PO every 8 hours for 5 days in addition to Ampicillin 2 gm IV every 6 hours for 2 days followed by Amoxicillin 250 mg PO every 8 hours for 5 days
• Azithromycin
Azithromycin 1 gm PO once or 500 mg PO followed by 250 mg PO daily for a total of 5 days in addition to Ampicillin 2 gm IV every 6 hours for 2 days followed by Amoxicillin 250 mg PO every 8 hours for 5 days

Locations

Country	Name	City	State
United States	Inova Fairfax Medical Campus	Falls Church	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Inova Fairfax Hospital

Country where clinical trial is conducted

United States, 

References & Publications (3)

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

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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Latency period	Time from PPROM to delivery between the two treatments	Number of days from PPROM to delivery, assessed up to 105 days