FB-CT2 Includes Two Prospective, Multi-centre Studies With a Medical Device in Hospital Settings: a Randomized, Dual-arm, Open-label Pilot Study in Spain, Followed by a Single-arm, Non-randomized, Open-label International Pivotal Study

Official title

Evaluation of the Safety and the Preterm Birth Predictive Capacity of the Clinical Investigation Device 'Cervisense TPTL': an International Clinical Study

Overview

The goal of this clinical trial is to evaluate the safety and the ability of a clinical investigation device (Cervisense TPTL) to predict the risk of spontaneous preterm birth in pregnant women with symptoms of threatened preterm labor (TPTL), between 28+0 and 36+6 weeks of gestation. The main questions it aims to answer are: Does the Cervisense TPTL device predict spontaneous preterm birth within 7 days? Is the device safe and technically reliable in a hospital setting? Researchers will conduct a Pilot Study (randomized, dual-arm) followed by a Pivotal Study (single-arm) to assess technical feasibility and predictive performance. Participants will undergo an intravaginal measurement of cervical stiffness using the Cervisense Intravaginal Probe. They will be followed for 14 days after the assessment to record delivery outcomes and any adverse events.

Detailed description

The study titled "Evaluation of the safety and the preterm birth predictive capacity of the clinical investigation device 'Cervisense TPTL': an international clinical study" is designed to assess both the safety and performance of the Cervisense TPTL device in predicting spontaneous preterm birth. It is being conducted across various Gynaecology, Obstetrics, and Emergency Services in hospitals throughout Spain and Germany.

Cervisense TPTL is the investigational product being evaluated. It includes two components: the Cervisense Intravaginal Probe V0.1, which measures cervical stiffness, and the Fine Birth algorithm, which combines the measurement with clinical data to assess the short-term risk of spontaneous preterm labor.

The device is intended for use in pregnant women showing symptoms of threatened preterm labor (TPTL), with intact amniotic membranes and a single fetus, between 28 weeks and 36 weeks plus 6 days of gestation. Its purpose is to determine the risk of spontaneous preterm birth within the following 7 days.

The clinical investigation is structured in two phases. The pilot study is a randomized, dual-arm, open-label, interventional, multi-centre study conducted in Spain. Participants are randomized 1:1 to receive either the standard of care or the Cervisense evaluation. The pivotal study is non-randomized and single-arm, also open-label and interventional, conducted at a larger scale across multiple centres in both Spain and Germany.

The main goal is to confirm that the device is safe to use and reliable in clinical settings. For safety, all adverse events associated with the use of the device are documented and analyzed in terms of severity, duration, and required intervention. Special attention is given to potential complications such as tissue trauma or infection. To ensure unbiased evaluation, a Clinical Events Committee and a Data Safety Monitoring Board have been established to independently review adverse events and guide study continuation.

Inclusion Criteria:

* Female ≥18 years * Singleton pregnancy * Live fetus, 28w+0d-36w+6d GA * Intact membranes * Cervical dilatation \<2 cm * Signed informed consent * Regular uterine contractions (≥8/60 min) (Pivotal only)

Exclusion Criteria:

* Latex allergy * Prolapsed membranes * Fetal malformation * Fetal infection * Vaginal bleeding (severe or persistent) * Cervical cerclage * Müllerian anomalies * Pessary use * Regular uterine contractions (reported by patient) (Pilot only) * History of preterm birth or TPTL (Pilot only) * Vasa/placenta previa (Pilot only) * Gastrointestinal or urinary infections (Pivotal only)

Interventions

• Device Cervisense Intravaginal Probe V0.1 cervical stiffness evaluation.
  The Cervisense Intravaginal Probe V0.1 measures cervical stiffness. It is an in-vivo predictive technology that, by using torsional waves, quantifies the mechanical properties (specifically the shear modulus, or resistance of the cervix to shear deformation (kPa), of cervical tissue with extremely high precision. Torsional wave is a type of mechanical wave characterized by a rotational motion and low energy levels (it uses 1000 times less energy than other mechanical waves such as ultrasound). T
• Device Transvaginal ultrasound
  Cervicometry measured with transvaginal ultrasound

Primary outcome measures

• ≥90% Specificity and ≥50% Sensitivity for predicting spontaneous preterm birth within 7 days (Pivotal Phase) [Time frame: From enrollment until delivery]
• Document and analyse all adverse events related to device use (severity, duration, intervention) (Pilot and Pivotal Phases) [Time frame: From enrollment until delivery]
• Technical problems ratio (Pilot Phase) [Time frame: From enrollment until the use of the device]
• Probe repeatability (Pilot Phase) [Time frame: From enrollment until the use of the device]
• Valid measurements obtained (Pilot Phase) [Time frame: From enrollment until the use of the device]

Secondary outcome measures (9)

• Monitor labour progression indicators (Pilot and Pivotal Phases) [Time frame: From enrollment until the 14-days follow-up]
• Monitor trauma indicators (e.g., petechiae, bleeding) (Pilot and Pivotal Phases) [Time frame: From enrollment until the 14-days follow-up]
• VAS pain score ≤3 (mild/no pain) (Pilot and Pivotal Phases) [Time frame: From enrollment until the use of the device]
• Specificity, Sensitivity, PPV, NPV within 10 and 14 days (Pivotal Phase) [Time frame: From enrollment until delivery]
• Subgroup analysis (gestational age, obstetric history) (Pivotal Phase) [Time frame: From enrollment until delivery]
• Training performance (Pivotal Phase) [Time frame: From enrollment until delivery]
• Operator satisfaction (SUS) (Pilot and Pivotal Phases) [Time frame: From enrollment until the use of the device]
• Comparison with PartoSure and cervical length (at 7, 10, 14 days) (Pivotal Phase) [Time frame: From enrollment until delivery]
• Degree of success obtained during the use of the Cervisense Intravaginal Probe (Pilot Phase) [Time frame: From enrollment until the use of the device]

Eligibility criteria

Inclusion criteria

• Female ≥18 years
• Singleton pregnancy
• Live fetus, 28w+0d-36w+6d GA
• Intact membranes
• Cervical dilatation <2 cm
• Signed informed consent
• Regular uterine contractions (≥8/60 min) (Pivotal only)

Exclusion criteria

• Latex allergy
• Prolapsed membranes
• Fetal malformation
• Fetal infection
• Vaginal bleeding (severe or persistent)
• Cervical cerclage
• Müllerian anomalies
• Pessary use
• Regular uterine contractions (reported by patient) (Pilot only)
• History of preterm birth or TPTL (Pilot only)
• Vasa/placenta previa (Pilot only)
• Gastrointestinal or urinary infections (Pivotal only)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Single group

Masking

Open label

Primary purpose

Screening

Study locations

Spain · 14 centers

• H. Universitario de A Coruña — A Coruña
• H. Clínic de Barcelona — Barcelona
• H. Sant Joan de Déu — Barcelona
• H. Vall d'Hebron — Barcelona
• H. Universitario de Basurto — Bilbao
• H. Universitario de Cruces — Bilbao
• H. Universitario de Donostia — Donostia / San Sebastian
• H. Universitario San Cecilio — Granada
• … and 6 more centers

Publications

• Papiernik E, Bouyer J, Collin D, Winisdoerffer G, Dreyfus J. Precocious cervical ripening and preterm labor. Obstet Gynecol. 1986 Feb;67(2):238-42. doi: 10.1097/00006250-198602000-00014. PMID 3945433
• Parra-Saavedra M, Gomez L, Barrero A, Parra G, Vergara F, Navarro E. Prediction of preterm birth using the cervical consistency index. Ultrasound Obstet Gynecol. 2011 Jul;38(1):44-51. doi: 10.1002/uog.9010. PMID 21465603
• Molina FS, Pardo L, Munoz MD, Aiartzaguena A, Valladolid A, Blanco JE, Burgos J, Gil MM. Reproducibility and usability assessment of the novel Fine Birth device for threatened preterm labor diagnosis. Am J Obstet Gynecol MFM. 2023 Jul;5(7):100982. doi: 10.1016/j.ajogmf.2023.100982. Epub 2023 Apr 23. PMID 37094638
• Melchor JC, Navas H, Marcos M, Iza A, De Diego M, Rando D, Melchor I, Burgos J. Predictive performance of PAMG-1 vs fFN test for risk of spontaneous preterm birth in symptomatic women attending an emergency obstetric unit: retrospective cohort study. Ultrasound Obstet Gynecol. 2018 May;51(5):644-649. doi: 10.1002/uog.18892. Epub 2018 Mar 26. PMID 28850753
• Melchor JC, Khalil A, Wing D, Schleussner E, Surbek D. Prediction of preterm delivery in symptomatic women using PAMG-1, fetal fibronectin and phIGFBP-1 tests: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018 Oct;52(4):442-451. doi: 10.1002/uog.19119. Epub 2018 Sep 4. PMID 29920825
• Masso P, Callejas A, Melchor J, Molina FS, Rus G. In Vivo Measurement of Cervical Elasticity on Pregnant Women by Torsional Wave Technique: A Preliminary Study. Sensors (Basel). 2019 Jul 24;19(15):3249. doi: 10.3390/s19153249. PMID 31344796
• Jackson GM, Ludmir J, Bader TJ. The accuracy of digital examination and ultrasound in the evaluation of cervical length. Obstet Gynecol. 1992 Feb;79(2):214-8. doi: 10.3109/01443619209013646. PMID 1731287
• Horinouchi T, Yoshizato T, Muto M, Fujii M, Kozuma Y, Shinagawa T, Morokuma S, Kakuma T, Ushijima K. Gestational age-related changes in shear wave speed of the uterine cervix in normal pregnancy at 12-35 weeks' gestation. J Perinat Med. 2019 May 27;47(4):393-401. doi: 10.1515/jpm-2018-0250. PMID 30817303

Identifiers

NCT: NCT06968364 · FB-CT2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗