Antibiotics Study in Preterm Premature Rupture of the Membranes (PPROM)

Randomized Phase III Trial of Cefazolin or Combination of Cefazolin and Erythromycin or Cefazolin and Clarithromycin in Women With Preterm Premature Rupture of the Membranes

The purpose of this study is to compare the efficacy on maternal infection, chorioamnionitis and neonatal morbidity and mortality, and to review the evidence and provide recommendations on the use of antibiotics in PPROM.

Study Overview

• Status: Completed
• Conditions: Preterm Premature Rupture of the Membranes
• Intervention / Treatment: Drug: cefazolin, erythromycin, clarithromycin

Detailed Description

Despite major advances in perinatal care, preterm delivery is still the predominant cause of perinatal mortality and a major cause of neurological morbidity and mortality. Although the determinants of preterm labor and delivery are uncertain, evidence suggests intrauterine infection is a contributing factor. Antibiotic therapy for women in preterm premature rupture of membranes has been a routine practice. However the optimal regimen remains unclear and the choice of latency antibiotic regimen is at the discretion of admitting physician. The group 1 is treated only with cefazolin (1.0mg iv every 6 hours for 7 days). The group 2 is given a combination of cefazolin(1.0mg iv every 6 hours for 7 days) and erythromycin(250mg p.o. four times a day for 7 days). In group 3, clarithromycin (500mg p.o. 4 times a day for 7 days) was treated with cefazolin(1.0mg iv every 6 hours for 7 days). This study is designed to compare the efficacy on maternal infection, chorioamnionitis and neonatal morbidity and mortality and to review the evidence and provide recommendations on the use of antibiotics, especially by comparing the combination regimen in PPROM.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• PPROM, PA 23+0~33+0wks
• ROM <48 hrs before randomization
• singleton
• Cervical dilatation <3cm
• uterine contraction less than 4 times per 1 hr

Exclusion Criteria:

• Major fetal malformation
• Multifetal pregnancy
• Rupture of the membrane >8hrs before randomization
• Prior antibiotics use at local clinic before referral
• Vaginal bleeding
• IIOC (incompetent internal os of cervix)
• Placenta previa
• Gestational diabetes or overt diabetes
• Hypertensive disorders in pregnancy
• Liver cirrhosis
• Acute renal failure
• IUGR(Intrauterine growth restriction)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: cefazolin	Drug: cefazolin, erythromycin, clarithromycin; Antibiotics regimen was one of cefazolin or cefazolin plus erythromycin or cefazolin plus clarithromycin. Intravenous 1g cefazolin was given every 6 hours after negative result skin test for allergic reaction. With cefazolin plus erythromycin group or cefazolin plus clarithromycin, cefazolin was given with same protocol and 250mg oral erythromycin every 6 hours or 500mg oral clarithromycin every 12 hours was added. All antibiotics were given for 7 days or until delivery.
Active Comparator: cefazolin plus erythromycin; cefazolin, erythromycin	Drug: cefazolin, erythromycin, clarithromycin; Antibiotics regimen was one of cefazolin or cefazolin plus erythromycin or cefazolin plus clarithromycin. Intravenous 1g cefazolin was given every 6 hours after negative result skin test for allergic reaction. With cefazolin plus erythromycin group or cefazolin plus clarithromycin, cefazolin was given with same protocol and 250mg oral erythromycin every 6 hours or 500mg oral clarithromycin every 12 hours was added. All antibiotics were given for 7 days or until delivery.
Active Comparator: cefazolin plus clarithromycin	Drug: cefazolin, erythromycin, clarithromycin; Antibiotics regimen was one of cefazolin or cefazolin plus erythromycin or cefazolin plus clarithromycin. Intravenous 1g cefazolin was given every 6 hours after negative result skin test for allergic reaction. With cefazolin plus erythromycin group or cefazolin plus clarithromycin, cefazolin was given with same protocol and 250mg oral erythromycin every 6 hours or 500mg oral clarithromycin every 12 hours was added. All antibiotics were given for 7 days or until delivery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal composite morbidity	respiratory distress syndrome(RDS); bronchopulmonary dysplasia(BPD); intraventricular hemorrhage(IVH,≥grade 3); retinopathy of prematurity(ROP,≥grade 3); necrotizing enterocolitis(NEC,≥stage 2); proven neonatal sepsis	Participants will be followed for duration of hospital day after delivery, an expected average of 8 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of abnormal brain sonography		Participants will be followed for duration of hospital day after delivery, an expected average of 8 weeks.
infantile neurologic outcome	The outcome was evaluated in five sub-domains (development, neurologic examination, Bayley Scales of Infant Development-II, vision, and hearing). The final outcome scale was divided into normal, mild, moderate, and severe disability.	at 6 months and 1 year of corrected age

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Soo-Young Oh, M.D., PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: July 19, 2011
• First Submitted That Met QC Criteria: July 22, 2011
• First Posted (Estimate): July 25, 2011

Study Record Updates

• Last Update Posted (Estimate): August 8, 2011
• Last Update Submitted That Met QC Criteria: August 5, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Preterm Premature Rupture of Fetal Membranes; antibiotic therapy
• Additional Relevant MeSH Terms: Wounds and Injuries; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Rupture; Premature Birth; Fetal Membranes, Premature Rupture; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin stearate; Clarithromycin; Cefazolin
• Other Study ID Numbers: 2005-04-003

Drug and device information, study documents

• 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