Antibiotics Study in Preterm Premature Rupture of the Membranes

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Preterm Premature Rupture of the Membranes

Intervention / Treatment
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* Drug: cefazolin, erythromycin, clarithromycin


Participation Criteria
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Eligibility Criteria
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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)
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: cefazolin<br> | Drug: cefazolin, erythromycin, clarithromycin<br>* 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.<br>|
| Active Comparator: cefazolin plus erythromycin<br>cefazolin, erythromycin | Drug: cefazolin, erythromycin, clarithromycin<br>* 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.<br>|
| Active Comparator: cefazolin plus clarithromycin<br> | Drug: cefazolin, erythromycin, clarithromycin<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm Premature Rupture of Fetal Membranes, antibiotic therapy