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

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

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.

Study Overview

• Status: Terminated
• Conditions: Fetal Membranes, Premature Rupture
• Intervention / Treatment: Procedure: Retention of Cerclage; Procedure: Removal vs. Retention of Cervical Cerclage; Procedure: Removal of Cerclage

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85202
      • Desert Good Samaritan Hospital
    • Phoenix, Arizona, United States, 85006
      • Banner Good Samaritan Hospital
    • Tucson, Arizona, United States, 85712
      • Tucson Medical Center
  • California
    • Laguna Hills, California, United States, 92653
      • Saddleback Memorial Medical Center
    • Long Beach, California, United States, 90801-1428
      • Long Beach Memorial Medical Center
    • Orange, California, United States, 92868
      • University of Southern California-Irvine Medical Center
    • San Jose, California, United States, 95124
      • Good Samaritan Hospital
  • Colorado
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80110
      • Swedish Medical Center
    • Denver, Colorado, United States, 80218
      • Presbyterian/St Luke's Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06504
      • Yale New-Haven Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Louisiana
    • Shreveport, Louisiana, United States, 60612
      • Lousiana State University Health Science
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Hutzel Women's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital, Kansas City
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Sunrise Medical Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The University Hospital
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Sacred Heart Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Children's Hospital-Texas Center for Fetal Assessment
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. 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
2. Spontaneous rupture of membranes 22-32 weeks
3. Singleton or twin gestation
4. Shirodkar or McDonald cerclage in place > 1 week

Exclusion Criteria:

1. Active labor (> 8 uterine contractions [UCs] per hour)
2. Chorioamnionitis as defined by temperature > 38 plus fetal tachycardia or uterine tenderness
3. Placenta previa or undiagnosed vaginal bleeding
4. Nonreassuring fetal status by nonstress test (NST) or biophysical profile (BPP)
5. Mature pulmonary studies
6. Positive gram stain, culture, white blood cells (WBC) > 30, or glucose < 14 on amniocentesis
7. Major fetal anomaly
8. Presentation > 48 hours after rupture of membranes
9. abdominal cerclage
10. Cerclage done for symptomatic cervical dilation (cervix dilated > 3 cm)
11. Post amniocentesis membrane rupture (rupture which occurs within one week of amniocentesis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Birth weight	at birth
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
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

Collaborators and Investigators

• Sponsor: Obstetrix Medical Group

Publications and helpful links

General Publications

• Treadwell MC, Bronsteen RA, Bottoms SF. Prognostic factors and complication rates for cervical cerclage: a review of 482 cases. Am J Obstet Gynecol. 1991 Sep;165(3):555-8. doi: 10.1016/0002-9378(91)90283-w.
• American College of Obstetricians and Gynecologists. Preterm Labor. Technical Bulletin no. 206,1995.
• McElrath TF, Norwitz ER, Lieberman ES, Heffner LJ. Management of cervical cerclage and preterm premature rupture of the membranes: should the stitch be removed? Am J Obstet Gynecol. 2000 Oct;183(4):840-6. doi: 10.1067/mob.2000.108870.
• Jenkins TM, Berghella V, Shlossman PA, McIntyre CJ, Maas BD, Pollock MA, Wapner RJ. Timing of cerclage removal after preterm premature rupture of membranes: maternal and neonatal outcomes. Am J Obstet Gynecol. 2000 Oct;183(4):847-52. doi: 10.1067/mob.2000.109039.
• Ludmir J, Bader T, Chen L, Lindenbaum C, Wong G. Poor perinatal outcome associated with retained cerclage in patients with premature rupture of membranes. Obstet Gynecol. 1994 Nov;84(5):823-6.
• Naylor CS, Gregory K, Hobel C. Premature rupture of the membranes: an evidence-based approach to clinical care. Am J Perinatol. 2001 Nov;18(7):397-413. doi: 10.1055/s-2001-18699. Erratum In: Am Fam Physician. 2015 Jun 1;91(11):750.
• Galyean A, Garite TJ, Maurel K, Abril D, Adair CD, Browne P, Combs CA, How H, Iriye BK, Kominiarek M, Lu G, Luthy D, Miller H, Nageotte M, Ozcan T, Porto M, Ramirez M, Sawai S, Sorokin Y; Obstetrix Perinatal Collaborative Research Network. Removal versus retention of cerclage in preterm premature rupture of membranes: a randomized controlled trial. Am J Obstet Gynecol. 2014 Oct;211(4):399.e1-7. doi: 10.1016/j.ajog.2014.04.009. Epub 2014 Apr 12.

Helpful Links

• Protocols' home page on the sponsor's Web site. Click on Protocols and then click the Protocol "Removal vs. Retention of Cerclage in PPROM" for more information about this study.

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): April 1, 2014

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (ESTIMATE): September 20, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): December 19, 2014
• Last Update Submitted That Met QC Criteria: December 17, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: PPROM; Cerclage; Preterm Premature Rupture of the Membranes with Cerclage
• Additional Relevant MeSH Terms: Wounds and Injuries; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Rupture; Premature Birth; Fetal Membranes, Premature Rupture
• Other Study ID Numbers: OBX0002 (OTHER: Obstetrix CREQ Protocol Number)