Treatment of ppROM With Erythromycin vs. Azithromycin Trial

NCT03060473 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 16-0323
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

Brief Summary

Preterm premature rupture of membranes (PPROM) complicates 4% of pregnancies annually. This pregnancy complication is a major contributor to preterm births and results in neonatal morbidity and mortality. The current standard of care for PPROM subjects between the gestational age of 24 weeks and 0 days and 33 weeks and 6 days, is to administer ampicillin and erythromycin for a total of 7 days. Erythromycin can cause GI upset and some subjects do not tolerate this regimen over the course of 7 days. In addition, there is a national shortage of erythromycin, and published expert opinion proposed to use a second-generation macrolide (azithromycin) instead of erythromycin. Azithromycin can be taken once daily, is cheaper than erythromycin and has less GI upset adverse effects. The investigators' objective is to compare the effectiveness of the 2 regimens in prolonging pregnancy after PPROM. The investigators' working hypothesis is that there is no measurable difference in the primary outcome between the group randomized to the azithromycin regimen versus the group randomized to the erythromycin regimen.

Conditions

Preterm Premature Rupture of Membranes (PPROM)

Keywords

PPROM; Azithromycin; Erythromycin

Outcome Measures

Primary Outcomes (1)

• Proportion of Women Still Pregnant by Day 7

  Proportion of women still pregnant by day 7 after the diagnosis of PPROM is made. The investigators' working hypothesis is that there is no measurable difference in the primary outcome between the group randomized to the azithromycin regimen versus the group randomized to the erythromycin regimen

  7 days

Secondary Outcomes (1)

• Latency Defined as Interval From PPROM to Delivery.

  7 days

Study Arms (2)

Azithromycin

EXPERIMENTAL

Ampicillin 2 gm IV every 6 hours followed by amoxicillin 500 mg PO every 8 hours with Azithromycin 1 gm PO once at randomization.

Drug: Azithromycin; Drug: Ampicillin; Drug: Amoxicillin

Erythromycin

ACTIVE COMPARATOR

Ampicillin 2 gm IV every 6 hours followed by amoxicillin 250 mg PO every 8 hours for 5 days with erythromycin 250 mg IV every 6 hours for 48 hours followed by 500 mg PO every 8 hours for 5 days.

Drug: Erythromycin; Drug: Ampicillin; Drug: Amoxicillin

Interventions

Azithromycin DRUG

Azithromycin 1 gm PO once

Azithromycin

Erythromycin DRUG

Erythromycin 250 mg IV every 6 hours for 48 hours followed by 500 mg PO every 8 hours for 5 days.

Erythromycin

Ampicillin DRUG

Ampicillin 2 gm IV every 6 hours for 2 days

Azithromycin; Erythromycin

Amoxicillin DRUG

Amoxicillin 500 mg PO every 8 hours for 5 days (Azithromycin ARM) Amoxicillin 250 mg PO every 8 hours for 5 days (Erythromycin ARM)

Azithromycin; Erythromycin

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Study is to be carried out on pregnant patients with diagnosis of PPROM.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Maternal age ≥ 18 years and \<50 years
• Pregnant women between the gestational age 23 6/7 and 32 6/7 weeks
• Singleton pregnancy
• Preterm premature rupture of membranes, determined clinically
• Cervical dilation visually ≤ 5cm on sterile speculum exam.
• Planned delivery at John Sealy Hospital (JSH)

You may not qualify if:

• Intrauterine fetal demise (no fetal heart beat identified and documented by two physicians)
• Any contraindication to expectant management (e.g. fetal compromise, chorioamnionitis, placental abruption)
• Cervical cerclage in place
• Placenta previa or other known placental anomalies
• Contraindication to any of the antibiotics used (allergy to macrolides).
• Enrolled in another trial that may affect outcome.
• Clinical chorioamnionitis or any other active bacterial infection (e.g. pyelonephritis, pneumonia, abscess) at time of randomization: because standard antibiotic therapy for these conditions may confound trial intervention.
• No prenatal care (less than 2 prenatal visits)
• Non-resident subject who is unlikely to be followed-up after delivery
• Any fetal congenital anomaly.
• Significant liver disease defined as known cirrhosis or elevated transaminases of at least 3-fold upper limit of normal
• Significant renal disease defined as serum creatinine known to be \>2.0 mg/dl or on dialysis.
• Active congestive heart failure (EF\<45%) or pulmonary edema.
• Immunosuppressed subjects: i.e., taking systemic immunosuppressants or steroids (e.g. transplant subjects; not including steroids for lung maturity), HIV with CD4\<200, or other.

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead

Study Sites (3)

St. David's North Austin Medical Center

Austin, Texas, 78758, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Preterm Premature Rupture of the Membranes

Interventions

Azithromycin; Erythromycin; Ampicillin; Amoxicillin

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

No data collected. The protocol was closed early due to low accrual and deemed futile.

Results Point of Contact

• Title: Dr. Nkechinyere Emezienna
• Organization: University of Texas Medical Branch

nkemezie@utmb.edu

4097476651

Study Officials

• Nkechinyere Emezienna, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Single Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Allocation: Randomized Intervention model: Parallel Assignment

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: February 23, 2017
• Study Start: February 23, 2017
• Primary Completion: December 8, 2023
• Study Completion: December 8, 2023
• Last Updated: June 25, 2024
• Results First Posted: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)