Fetal Membranes, Premature RupturePhase 4PROMCerclageNCT00201656
Removal Versus Retention of Cerclage in Preterm Premature Rupture of Membranes (PPROM)
A Phase 4 study testing Retention of Cerclage, Removal of Cerclage and Removal vs. Retention of Cervical Cerclage in people with Fetal Membranes, Premature Rupture, run by Obstetrix Medical Group at 23 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, women only
- Conditions the study is for
- Fetal Membranes, Premature Rupture
- What is being tested?
- Retention of Cerclage, Removal of Cerclage and Removal vs. Retention of Cervical Cerclage
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 23 sitesUnited States
- Study dates
- Nov 2004to Apr 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
United States23 sites
Erlanger Medical Center
Chattanooga, Tennessee, 37403
University of Illinois at Chicago
Chicago, Illinois, 60612
The University Hospital
Cincinnati, Ohio, 45219
Swedish Medical Center
Denver, Colorado, 80110
Presbyterian/St Luke's Hospital
Denver, Colorado, 80218
Rose Medical Center
Denver, Colorado, 80220
Hutzel Women's Hospital
Detroit, Michigan, 48201
Sacred Heart Medical Center
Eugene, Oregon, 97401
Memorial Hermann Children's Hospital-Texas Center for Fetal Assessment
Houston, Texas, 77030
Saint Luke's Hospital, Kansas City
Kansas City, Missouri, 64111
Evergreen Hospital
Kirkland, Washington, 98034
Saddleback Memorial Medical Center
Laguna Hills, California, 92653
Sunrise Medical Center
Las Vegas, Nevada, 89109
Long Beach Memorial Medical Center
Long Beach, California, 90801-1428
Desert Good Samaritan Hospital
Mesa, Arizona, 85202
Yale New-Haven Medical Center
New Haven, Connecticut, 06504
University of Southern California-Irvine Medical Center
Orange, California, 92868
Banner Good Samaritan Hospital
Phoenix, Arizona, 85006
University of Rochester Medical Center
Rochester, New York, 14642
Good Samaritan Hospital
San Jose, California, 95124
Swedish Medical Center
Seattle, Washington, 98122-4307
Lousiana State University Health Science
Shreveport, Louisiana, 60612
Tucson Medical Center
Tucson, Arizona, 85712
About this study
Official title: 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.
Read the 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.
- Conditions
- Fetal Membranes, Premature Rupture
- Being tested
- Retention of Cerclage, Removal of Cerclage, Removal vs. Retention of Cervical Cerclage
- Keywords
- PPROM, Cerclage, Preterm Premature Rupture of the Membranes with Cerclage
- Medical subject headings
- Fetal Membranes, Premature Rupture, Preterm Premature Rupture of the Membranes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retention of CerclageProcedure or surgery
Retain Cerclage until clinical removal is indicated by protocol
Removal of CerclageProcedure or surgery
Immediate removal of Cerclage following randomization
Removal vs. Retention of Cervical CerclageProcedure or surgery
Also called McDonald or Shirodkar Cerclage
Immediate removal of cerclage following randomization vs. retention of cerclage until labor, chorioamnionitis, or fetal distress
| Study group | Role | What they receive |
|---|---|---|
| 1 Retention of Cerclage | Active comparator | Group one = Subject whose Cerclage is retained after randomization. Receives: Procedure: Retention of Cerclage; Procedure: Removal vs. Retention of Cervical Cerclage |
| 2 - Removal of Cerclage | Active comparator | Group 2 = Subjects who will have cerclage removed after randomization Receives: Procedure: Removal of Cerclage; Procedure: Removal vs. Retention of Cervical Cerclage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Chorioamnionitis as defined by temperature > 38 plus fetal tachycardia or uterine tenderness
Measured: conception to birth
Composite neonatal outcome - any one of the following (for twins, either infant): Fetal or neonatal death
Measured: Birth to 28days of life
Respiratory distress syndrome
Measured: birth to 28days of life
Documented sepsis within 72 hours of delivery
Measured: birth to 72 hours after delivery
Grade 3 or 4 intraventricular hemorrhage
Measured: birth to 28days of life
Stage 2 or 3 necrotizing enterocolitis
Measured: birth to 28days of life
Neonatal intensive care unit (NICU) stay
Measured: birth to 28days of life
Birth weight
Measured: at birth
Estimated gestational age (EGA) at delivery
Measured: at delivery
Postpartum endometritis
Measured: birth to 28days of life
Maternal sepsis
Measured: birth to 28days following delivery
Latency
Measured: labor to delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startNov 2004
- Primary completionNov 2013
- Study completionApr 2014
Why it stopped: This trial was terminated following a futility analysis confirming futility of continuing the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Fetal Membranes, Premature RuptureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Obstetrix Medical Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kimberly Maurel, RN, MSN, CNS, Study director, Obstetrix Medical Group, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00201656
- Sponsor's protocol ID
- OBX0002
- Other IDs
- OBX0002
- Acronym
- PROMCerclage
- Status last verified
- Dec 2014
- First submitted
- 13 Sep 2005
- Last updated
- 19 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 1892180American 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.
PubMed 11035323Jenkins 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.
PubMed 11035324Ludmir 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.
PubMed 7936520Naylor 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.
PubMed 11731894Galyean 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.
PubMed 24726507
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Removal Versus Retention of Cervical Cerclage in Preterm Premature Rupture of Membranes-A Multicenter Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT00201656
- Acronym / sponsor ID
- PROMCerclage / OBX0002
- Conditions
- Fetal Membranes, Premature Rupture
- Keywords
- PPROM, Cerclage, Preterm Premature Rupture of the Membranes with Cerclage
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This trial was terminated following a futility analysis confirming futility of continuing the study
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Obstetrix Medical GroupIndustry (pharma, biotech, devices)
- Study start
- Nov 2004
- Primary completion
- Nov 2013 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 Retention of Cerclage | Active comparator | Procedure: Retention of Cerclage, Procedure: Removal vs. Retention of Cervical CerclageGroup one = Subject whose Cerclage is retained after randomization. |
| 2 - Removal of Cerclage | Active comparator | Procedure: Removal of Cerclage, Procedure: Removal vs. Retention of Cervical CerclageGroup 2 = Subjects who will have cerclage removed after randomization |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Retention of CerclageRetain Cerclage until clinical removal is indicated by protocol | Procedure or surgery | 1 Retention of Cerclage |
| Removal of CerclageImmediate removal of Cerclage following randomization | Procedure or surgery | 2 - Removal of Cerclage |
| Removal vs. Retention of Cervical CerclageAlso: McDonald or Shirodkar CerclageImmediate removal of cerclage following randomization vs. retention of cerclage until labor, chorioamnionitis, or fetal distress | Procedure or surgery | 1 Retention of Cerclage, 2 - Removal of Cerclage |
Primary outcome
Chorioamnionitis as defined by temperature > 38 plus fetal tachycardia or uterine tenderness
Time frame: conception to birth
Composite neonatal outcome - any one of the following (for twins, either infant): Fetal or neonatal death
Time frame: Birth to 28days of life
Respiratory distress syndrome
Time frame: birth to 28days of life
Documented sepsis within 72 hours of delivery
Time frame: birth to 72 hours after delivery
Grade 3 or 4 intraventricular hemorrhage
Time frame: birth to 28days of life
Stage 2 or 3 necrotizing enterocolitis
Time frame: birth to 28days of life
Neonatal intensive care unit (NICU) stay
Time frame: birth to 28days of life
Birth weight
Time frame: at birth
Estimated gestational age (EGA) at delivery
Time frame: at delivery
Postpartum endometritis
Time frame: birth to 28days of life
Maternal sepsis
Time frame: birth to 28days following delivery
Latency
Time frame: labor to delivery
Results and safety
The study was stopped early (reason given: This trial was terminated following a futility analysis confirming futility of continuing the study). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2014.
- Background: PubMed 1892180Treadwell 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.
- BackgroundAmerican College of Obstetricians and Gynecologists. Preterm Labor. Technical Bulletin no. 206,1995.
- Background: PubMed 11035323McElrath 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.
- Background: PubMed 11035324Jenkins 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.
- Background: PubMed 7936520Ludmir 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.
- Background: PubMed 11731894Naylor 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.
- Derived from this study: PubMed 24726507Galyean 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kimberly Maurel, RN, MSN, CNS study director
Obstetrix Medical Group, Inc.
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Retention of Cerclage, Removal of Cerclage and Removal vs. Retention of Cervical Cerclage in people with Fetal Membranes, Premature Rupture, run by Obstetrix Medical Group at 23 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: This trial was terminated following a futility analysis confirming futility of continuing the study). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Chorioamnionitis as defined by temperature > 38 plus fetal tachycardia or uterine tenderness (time frame: conception to birth). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00201656, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2014.