Cervical Stiffness Measurement in Cervical Insufficiency

• ClinicalTrials.gov Identifier: NCT04158401
• Recruitment Status: Completed
• First Posted: November 8, 2019
• Last Update Posted: September 21, 2022
• Sponsor: Tufts Medical Center
• Collaborator: Pregnolia AG
• Information provided by (Responsible Party): Tufts Medical Center

Tracking Information

• First Submitted Date: October 23, 2019
• First Posted Date: November 8, 2019
• Last Update Posted Date: September 21, 2022
• Actual Study Start Date: January 15, 2020
• Actual Primary Completion Date: June 15, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 7, 2019)

Cervical stiffness (Pcl) [ Time Frame: 5 minutes ]

The primary outcome will be cervical stiffness, Pcl in patients presenting for cerclage versus normal controls.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 7, 2019)

• Delivery data [ Time Frame: up to 10 months ]
  Patient delivery data including gestational age, mode of delivery and complications will be recorded
• Newborn outcomes [ Time Frame: up to 10 months ]
  Newborn outcomes including weight, APGARs and complications will be recorded

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cervical Stiffness Measurement in Cervical Insufficiency
• Official Title: Cervical Stiffness Measurement in Cervical Insufficiency

Brief Summary

The goal of this cross sectional study is to evaluate the differences in cervical stiffness between patients who present for cerclage placement versus normal pregnancies.

The central hypothesis is that women for whom a cerclage is indicated will have cervical stiffness measurements lower than normal controls. Cervical stiffness will be objectively measured by the closing pressure Pcl using the Pregnolia measurement device. This is performed during a speculum exam by placing the measurement probe on the ectocervix.

In current clinical care, there is no objective measurement of cervical stiffness. An accurate measurement of cervical stiffness that correlates with clinical outcome will advance the field. Successful completion of the current study will spark future studies that correlate cervical stiffness pcl in a prospective study.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: We are studying pregnant patients between 12w0d and 22w6d.

Condition

• Pregnancy Related
• Cervical Insufficiency
• Preterm Birth

Intervention

Device: Pregnolia

The Pregnolia measurement device (CE Mark for commercialization in the EU) will be used to measure the cervical stiffness (Pcl) on all subjects.

Study Groups/Cohorts

• Control group
  Pregnant patients between 12w0d and 22w0d who present for prenatal care.
  Intervention: Device: Pregnolia
• Cerclage group A
  Patients who present for a history-indicated cerclage placement.
  Intervention: Device: Pregnolia
• Cerclage group B
  Patients who present for an ultrasound-indicated cerclage placement.
  Intervention: Device: Pregnolia
• Cerclage group C
  Patients who present for an exam-indicated cerclage placement.
  Intervention: Device: Pregnolia

Publications *

• Lorenz JM. The outcome of extreme prematurity. Semin Perinatol. 2001 Oct;25(5):348-59. doi: 10.1053/sper.2001.27164.
• Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008 Jan 5;371(9606):75-84. doi: 10.1016/S0140-6736(08)60074-4.
• Gilbert WM, Nesbitt TS, Danielsen B. The cost of prematurity: quantification by gestational age and birth weight. Obstet Gynecol. 2003 Sep;102(3):488-92. doi: 10.1016/s0029-7844(03)00617-3.
• Iams JD, Johnson FF, Sonek J, Sachs L, Gebauer C, Samuels P. Cervical competence as a continuum: a study of ultrasonographic cervical length and obstetric performance. Am J Obstet Gynecol. 1995 Apr;172(4 Pt 1):1097-103; discussion 1104-6. doi: 10.1016/0002-9378(95)91469-2.
• Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, Rubens C, Menon R, Van Look PF. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ. 2010 Jan;88(1):31-8. doi: 10.2471/BLT.08.062554. Epub 2009 Sep 25.
• Mazza E, Parra-Saavedra M, Bajka M, Gratacos E, Nicolaides K, Deprest J. In vivo assessment of the biomechanical properties of the uterine cervix in pregnancy. Prenat Diagn. 2014 Jan;34(1):33-41. doi: 10.1002/pd.4260.
• Hollenstein M, Bugnard G, Joos R, Kropf S, Villiger P, Mazza E. Towards laparoscopic tissue aspiration. Med Image Anal. 2013 Dec;17(8):1037-45. doi: 10.1016/j.media.2013.06.001. Epub 2013 Jun 19.
• Badir S, Bajka M, Mazza E. A novel procedure for the mechanical characterization of the uterine cervix during pregnancy. J Mech Behav Biomed Mater. 2013 Nov;27:143-53. doi: 10.1016/j.jmbbm.2012.11.020. Epub 2012 Dec 11.
• Badir S, Mazza E, Zimmermann R, Bajka M. Cervical softening occurs early in pregnancy: characterization of cervical stiffness in 100 healthy women using the aspiration technique. Prenat Diagn. 2013 Aug;33(8):737-41. doi: 10.1002/pd.4116. Epub 2013 Apr 29.
• Bauer M, Mazza E, Jabareen M, Sultan L, Bajka M, Lang U, Zimmermann R, Holzapfel GA. Assessment of the in vivo biomechanical properties of the human uterine cervix in pregnancy using the aspiration test: a feasibility study. Eur J Obstet Gynecol Reprod Biol. 2009 May;144 Suppl 1:S77-81. doi: 10.1016/j.ejogrb.2009.02.025. Epub 2009 Mar 13.
• Bauer M, Mazza E, Nava A, Zeck W, Eder M, Bajka M, Cacho F, Lang U, Holzapfel GA. In vivo characterization of the mechanics of human uterine cervices. Ann N Y Acad Sci. 2007 Apr;1101:186-202. doi: 10.1196/annals.1389.004. Epub 2007 Mar 15.
• Mazza E, Nava A, Bauer M, Winter R, Bajka M, Holzapfel GA. Mechanical properties of the human uterine cervix: an in vivo study. Med Image Anal. 2006 Apr;10(2):125-36. doi: 10.1016/j.media.2005.06.001. Epub 2005 Sep 6.
• Mazza E, Nava A, Hahnloser D, Jochum W, Bajka M. The mechanical response of human liver and its relation to histology: an in vivo study. Med Image Anal. 2007 Dec;11(6):663-72. doi: 10.1016/j.media.2007.06.010. Epub 2007 Jul 5.
• ACOG Practice Bulletin No.142: Cerclage for the management of cervical insufficiency. Obstet Gynecol. 2014 Feb;123(2 Pt 1):372-379. doi: 10.1097/01.AOG.0000443276.68274.cc.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 18, 2022): 136
• Original Estimated Enrollment (submitted: November 7, 2019): 140
• Actual Study Completion Date: June 15, 2022
• Actual Primary Completion Date: June 15, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Pregnant women over 18 years of age.
2. Singleton gestation.
3. Gestational ages between 12w0d and 22w6d.
4. Candidates for cerclage
5. Normal controls, which will be matched to cerclage subjects by gestational age and parity

Exclusion Criteria:

1. Multiple gestation pregnancy.
2. Pregnancy complications: Premature rupture of membranes, Placental abruption, Placenta previa/accreta.
3. Chorioamnionitis
4. Preterm contractions
5. History of cervical surgery (LEEP, trachelectomy, conization).
6. Mullarian anomaly
7. Known carrier or HIV or Hepatitis B/C
8. Active genital infection
9. Communication problems (cognitively impaired adults unable to give consent)
10. Cerclage placement already performed this pregnancy

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Patients need to be pregnant.

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04158401
• Other Study ID Numbers: 13549
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Tufts Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Tufts Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Pregnolia AG

Investigators

• Principal Investigator: Michael House, MD; Tufts Medical Center

• PRS Account: Tufts Medical Center
• Verification Date: September 2022