Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Mechanical Environment Pregnancy With Short Cervix (ATOPS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03865108
Recruitment Status : Unknown
Verified April 2019 by Kristin Myers, Columbia University.
Recruitment status was:  Recruiting
First Posted : March 6, 2019
Last Update Posted : April 4, 2019
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Kristin Myers, Columbia University

Tracking Information
First Submitted Date  ICMJE February 22, 2019
First Posted Date  ICMJE March 6, 2019
Last Update Posted Date April 4, 2019
Actual Study Start Date  ICMJE June 5, 2017
Estimated Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2019)
Mechanical compliance index of the cervix [ Time Frame: Baseline (at diagnosis of short cervix), third trimester (approximately 26-30 weeks) ]
The mechanical compliance index of the cervix is the percentage of the cervical tissue above a 1.2 stretch threshold under a uniform IUP. This index is calculated using finite element computational methods, given the maternal anatomy and cervical stiffness measured from the aspiration tool. The mechanical compliance index of the cervix will be measured at both time points within the study timeframe, and the change of the mechanical compliance index between the two time points will be assessed. The main outcome parameter will be the mechanical compliance index at the baseline time point, and the other two outcome measures will be used as validation data points.
Original Primary Outcome Measures  ICMJE
 (submitted: March 5, 2019)
Mechanical compliance index of the cervix [ Time Frame: Baseline (at diagnosis of short cervix), third trimester (approximately 26-30 weeks) ]
The mechanical compliance index of the cervix is the percentage of the cervical tissue above a 1.2 stretch threshold under a uniform IUP. This index is calculated using finite element computational methods, given the maternal anatomy and cervical stiffness measured from the aspiration tool. We will measure the mechanical compliance index of the cervix at both time points within the study timeframe, and we will assess the change of the mechanical compliance index between the two time points. The main outcome parameter will be the mechanical compliance index at the baseline time point, and the other two outcome measures will be used as validation data points.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2019)
Number of participants with spontaneous preterm birth [ Time Frame: Pregnancy duration, an average of up to 40 weeks ]
The investigator will tally the number of women who receive Intervention of Pessary and experience spontaneous preterm birth
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mechanical Environment Pregnancy With Short Cervix
Official Title  ICMJE Quantifying the Mechanical Environment of Pregnancy Complicated With a Short Cervix With Ultrasound Imaging and Aspiration - Ancillary Study to the Trial of Pessary in Singleton Pregnancies Trial
Brief Summary

The objective of this study is to quantify the mechanical environment of pregnancies complicated by a short cervix and randomized in the Trial of Pessary in Singleton Pregnancies with a Short Cervix study with ultrasound imaging and aspiration.

Aim 1: To determine the biomechanical properties of a prematurely remodeled cervix.

Aim 2: To determine the impact of pessary placement on the biomechanical properties of a prematurely remodeled cervix and establish if the pessary reduces the mechanical load on the cervix through computer modeling informed by ultrasonographic measurement and cervical stiffness measurements.

Aim 3: To determine if the differences in the cervical biomechanical properties after pessary placement lead to improved birth outcomes as compared to the progesterone only group.

Detailed Description

In pregnancy the mother carries the growing fetus throughout gestation as her body prepares for delivery. This maternal preparation includes anatomical, physiological, and biochemical changes of the uterus, cervix, and ligaments that surround and support the uterus and cervix. For a successful term delivery, the uterus, cervix and supporting ligaments must remodel in a coordinated fashion to allow for adequate dilation and effacement of the cervix and delivery of the fetus.

Preterm birth (PTB) is the leading cause of neonatal death. Premature babies that survive face a significantly increased risk of long-term disabilities, such as mental retardation, learning and behavioral problems, cerebral palsy, seizures, respiratory problems, gastrointestinal problems and vision/hearing loss. PTB is also significant cost factor in healthcare. In 2003, a study in the US approximated neonatal costs to be $224,400 for a newborn that weighed 500-700g (extreme-severe preterm range) verse $1,000 at over 3,000g. These costs increase exponentially with decreasing gestational age and weight. In 2007, an Institute of Medicine report entitled "Preterm Birth" found that the 550,000 preemies born each year in the U.S. cost $26 billion annually, mostly related to prolonged care in neonatal intensive care units. The pathophysiology of PTB is multi-factorial and the degree of severity spans a wide range, with pregnancy outcomes depending on a combination of congenital, anatomical, obstetric, epidemiological, and biochemical factors. Because of these confounding factors PTB rates in the US and around the world are on the rise and diagnostic methods to identify high-risk women for PTB remain elusive.

Premature cervical remodeling which leads to softening/shortening of the cervix (i.e., a mechanical failure of the cervix) is one of the leading contributors to the birth of a severely preterm neonate. The true frequency and impact is unknown because diagnosing this condition remains elusive and the biomechanical environment of pregnancy is unknown. The pathophysiology is hypothesized to be multi-factorial leading to a common feature of a structurally weak and excessively soft cervix that is unable to remain closed and to support the fetus. Recently, it has been demonstrated that these preterm cervical changes may in some cause premature cervical shortening as measured by transvaginal ultrasound imaging. When this occurs, treatment with progesterone suppositories has been demonstrated to reduce the risk of preterm delivery. However, this treatment is not effective in many cases; probably because a short cervix is a late manifestation of the underlying biostructural alterations in the uterus, cervix and supporting ligaments.

Many clinically-relevant advances in the field of orthopedics and gynecology (i.e., assessing the causes of uterine prolapse have been attributed to the accurate biomechanical modeling of the anatomy and tissue properties using finite element analysis (FEA). FEA is a computer simulation that computes tissue stretch (i.e., tissue strain), tissue stress, and reaction forces when external mechanical forces are applied to the system given the tissue's geometric shape and mechanical properties. Lastly, directly measuring the mechanical stiffness of the uterine cervix through use of a simple aspiration device has shown that in normal pregnancy cervical tissue softens starting in the 1st trimester and continues until dilation. These studies have also shown that using a simple mechanical aspirator applied to the end of the cervix protruding into the vaginal canal has zero adverse effects on the patient, where the measurement can be performed during a standard speculum exam.

The cervical pessary has been proposed as an additional option for treatment in pregnancies with a short cervix. It offers additional theoretical benefits over the cerclage, in that it does not require surgical intervention. Its proposed mechanisms of action include a) angling the cervix toward the posterior, bringing the external os toward the sacrum, b) mechanically closing the cervix with the constraining geometry of the device, and c) preserving the mucous plug. These mechanisms of action involve lowering the mechanical stresses on the area of the internal os, potentially modifying the release of the enzymes and inflammatory markers involved in the preterm birth pathway. However, it is still unknown if the pessary relieves the mechanical load on the cervix because a biomechanical investigation of its function has not been performed. Therefore, the investigator plans to study a group of women with a short cervix randomized in an existing trial: AAAR1353 - A Randomized Trial of Pessary in Singleton Pregnancies with a Short Cervix (TOPS) in order to better understand the function and effect of the cervical pessary on the biomechanical support of the cervix in addition to its effect on its tissue properties and structural integrity. If a specific maternal utero-cervical phenotype can be located, where the placement of the cervical pessary reduces the mechanical load on the cervical internal os and therefore leads to a decreased incidence of preterm birth, then a more personalized treatment may be possible for patients who fall within this specific phenotype in the future.

For the substudy, a total of 36 women will be recruited and randomized through the existing TOPS trial (18 randomized to Pessary and Progesterone and 18 randomized to progesterone only). Obstetric and gynecologic history, age, race, body mass index, smoking history, and outcome of the current pregnancy will be recorded for all patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The two arms are not randomized under this sub study but carried over from the existing TOPS trial.
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Preterm Birth
Intervention  ICMJE
  • Procedure: Ultrasound imaging
    This standard of care procedure is being done for research purposes and used to collect information and measure the maternal and fetal anatomy.
    Other Name: Sonography
  • Procedure: Cervical speculum examination
    This standard of care procedure is being done for research purposes and used to collect tissue and measure the strength and stiffness of cervix.
    Other Name: Cervical aspiration
Study Arms  ICMJE
  • Experimental: Pessary and Progesterone
    Women already receiving a pessary in addition to the standard progesterone through the TOPS trial will undergo ultrasound imaging and cervical speculum examination for information collection.
    Interventions:
    • Procedure: Ultrasound imaging
    • Procedure: Cervical speculum examination
  • Placebo Comparator: Progesterone only
    Women already receiving the standard progesterone only will undergo ultrasound imaging and cervical speculum examination for information collection.
    Interventions:
    • Procedure: Ultrasound imaging
    • Procedure: Cervical speculum examination
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: March 5, 2019)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2019
Estimated Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Singleton gestation.

    • Twin gestation reduced to singleton either spontaneously or therapeutically, is not eligible unless the reduction occurred before 13 weeks 6 days project gestational age.
    • Higher order multifetal gestations reduced to singletons are not eligible.
  • Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound as described in Gestational Age.
  • Cervical length on transvaginal examination of less than or equal to 20 mm within 10 days prior to randomization by a study certified sonographer. There is no lower cervical length threshold.

Exclusion Criteria:

  • Women who are ineligible for the TOPS trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03865108
Other Study ID Numbers  ICMJE AAAO4956 sub-study
3UG1HD040485-18S1 ( U.S. NIH Grant/Contract )
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
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Kristin Myers, Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Principal Investigator: Kristin Myers, PhD Associate Professor of Mechanical Engineering
Study Director: Mirella Mourad, MD Assistant Professor of Obstetrics and Gynecology
PRS Account Columbia University
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP