Removal Versus Retention of Cerclage in Preterm Premature Rupture of Membranes (PPROM)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether retention of cervical cerclage after PPROM improves latency (without a significant increase in chorioamnionitis) and lessens neonatal morbidity.

Detailed Description
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The placement of cervical cerclage is standard of care for women who experience incompetent cervix. Treadwell et al, published the largest retrospective review of 482 patients receiving cerclage (364 elective and 118 emergent). They found premature rupture of membranes (PROM) in 38% of the subjects with 9% delivering <27 weeks. Preterm birth is the cause of at least 75% of neonatal deaths that are not due to congenital malformations. The question of whether to remove cerclage after preterm premature rupture of membranes (PPROM) is one of the unresolved controversies in obstetrics because the few available studies are retrospective, all have small numbers of patients, and the studies have given conflicting results regarding the safety of retaining a cerclage after preterm premature rupture of the membranes. It is unclear from the retrospective studies whether latency (the interval from membrane rupture to the onset of labor) is prolonged with retention of the suture. Furthermore, some, but not all studies suggest an increase in major infectious maternal morbidity and possibly neonatal morbidity. For this reason, clinicians vary greatly in deciding on whether to remove a cerclage in a patient with PPROM and either practice is currently an acceptable standard. This is a fairly rare complication, the combination of PPROM in a patient with cerclage in place only occurs in about 1-3/1000 pregnant women. Thus it has been impossible to study this problem prospectively in any single institution. The establishment of the Obstetrix Collaborative Research Group affords the unique opportunity to study this rare complication. Obstetrix manages 19 practices of Perinatologists around the U.S. and Mexico and is comprised of nearly 100 such subspecialists. This problem is most often referred to a Perinatologist when it occurs, so it is not unusual for these practices to see 5 - 10 such patients per year. Obstetrix fully funds the infrastructure of this research group and inclusion in this study will not alter the cost of patient care in either group as there is virtually no cost in removing the cerclage and all these patients are kept in hospital until delivery when membranes rupture as standard of care. This is a multicenter trial. The purpose is to determine whether retention of cerclage after preterm premature rupture of the membranes improves latency (without a significant increase in chorioamnionitis) and lessens neonatal morbidity.

Official Title
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Removal Versus Retention of Cervical Cerclage in Preterm Premature Rupture of Membranes-A Multicenter Randomized Clinical Trial

Conditions
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Fetal Membranes, Premature Rupture

Intervention / Treatment
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* Procedure: Retention of Cerclage
* Procedure: Removal of Cerclage
* Procedure: Removal vs. Retention of Cervical Cerclage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A previously placed prophylactic cerclage defined as any cerclage done < 23 6/7 weeks including those done for previous history of cervical incompetence, asymptomatic cervical shortening (regardless of effacement) and asymptomatic cervical dilation < 3 cm Spontaneous rupture of membranes 22-32 weeks Singleton or twin gestation Shirodkar or McDonald cerclage in place > 1 week Exclusion Criteria: Active labor (> 8 uterine contractions [UCs] per hour) Chorioamnionitis as defined by temperature > 38 plus fetal tachycardia or uterine tenderness Placenta previa or undiagnosed vaginal bleeding Nonreassuring fetal status by nonstress test (NST) or biophysical profile (BPP) Mature pulmonary studies Positive gram stain, culture, white blood cells (WBC) > 30, or glucose < 14 on amniocentesis Major fetal anomaly Presentation > 48 hours after rupture of membranes abdominal cerclage Cerclage done for symptomatic cervical dilation (cervix dilated > 3 cm) Post amniocentesis membrane rupture (rupture which occurs within one week of amniocentesis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 Retention of Cerclage<br>Group one = Subject whose Cerclage is retained after randomization. | Procedure: Retention of Cerclage<br>* Retain Cerclage until clinical removal is indicated by protocol<br>Procedure: Removal vs. Retention of Cervical Cerclage<br>* Immediate removal of cerclage following randomization vs. retention of cerclage until labor, chorioamnionitis, or fetal distress<br>* Other names: McDonald or Shirodkar Cerclage;|
| Active Comparator: 2 - Removal of Cerclage<br>Group 2 = Subjects who will have cerclage removed after randomization | Procedure: Removal of Cerclage<br>* Immediate removal of Cerclage following randomization<br>Procedure: Removal vs. Retention of Cervical Cerclage<br>* Immediate removal of cerclage following randomization vs. retention of cerclage until labor, chorioamnionitis, or fetal distress<br>* Other names: McDonald or Shirodkar Cerclage;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chorioamnionitis as defined by temperature > 38 plus fetal tachycardia or uterine tenderness |  | conception to birth | 
| Composite neonatal outcome - any one of the following (for twins, either infant): Fetal or neonatal death |  | Birth to 28days of life | 
| Respiratory distress syndrome |  | birth to 28days of life | 
| Documented sepsis within 72 hours of delivery |  | birth to 72 hours after delivery | 
| Grade 3 or 4 intraventricular hemorrhage |  | birth to 28days of life | 
| Stage 2 or 3 necrotizing enterocolitis |  | birth to 28days of life | 
| Neonatal intensive care unit (NICU) stay |  | birth to 28days of life | 
| Birth weight |  | at birth | 
| Estimated gestational age (EGA) at delivery |  | at delivery | 
| Postpartum endometritis |  | birth to 28days of life | 
| Maternal sepsis |  | birth to 28days following delivery | 
| Latency |  | labor to delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PPROM, Cerclage, Preterm Premature Rupture of the Membranes with Cerclage