To Optimize Antenatal Management of Women With Pre Term Labor Using Amniocentesis (OPTIM-PTL)

To Optimize Antenatal Management of Women Admitted With Pre Term Labor and Intact Membranes Using Multivariable Prediction Models: Multicenter Randomised Control Trial (OPTIM-PTL)

Implementation of prediction models of risk of spontaneous delivery within 7 days or of intra-amniotic infection in women with preterm labor and intact membranes

Study Overview

• Status: Recruiting
• Conditions: Preterm Birth; Preterm Labor; Amniocentesis Affecting Fetus or Newborn; Intra-amniotic Infection
• Intervention / Treatment: Drug: Steroid Drug; Drug: Tocolytic Agents

Detailed Description

To evaluate whether the implementation of prediction models of risk of spontaneous delivery within 7 days or of intra-amniotic infection:

1. Optimises antenatal management (regarding steroids, tocolysis, antibiotics, maternal length stay duration) without worsening perinatal outcomes.
2. It is a cost-effective strategy.
3. It improves neonatal outcome (in premature newborns <30 weeks), and reduces infectious maternal morbility.
4. It improves neurodevelopmental outcome at 1.2 and 5 years.

• Study Type: Interventional
• Enrollment (Anticipated): 340
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Teresa Cobo, MD,PhD; Phone Number: 7281 +34 93 227 54 00; Email: tcobo@clinic.cat
• Study Contact Backup: Name: Ana B Sánchez García, Bsc; Phone Number: 7281 +34 93 227 54 00; Email: absanchez@clinic.cat

Study Locations

• Spain
  • Barcelona, Spain, 08828
    • Recruiting
    • Fundació Recerca Biomèdica Clínica
    • Contact: Teresa Cobo, MD, PhD; Phone Number: 34932275600; Email: tcobo@clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant women with singleton pregnancies admitted with a diagnosis of preterm labor between 23.0 and 34.6 weeks, not in labor at randomization and who do not meet exclusion criteria.

Exclusion Criteria:

• Women who do no accept to be part of the study
• Maternal age < 18 years
• Multiple gestations
• Clinical chorioamnionitis at randomization (defined by the presence of fever above 38 celsius degrees (ºC), fetal tachycardia (>160 heart beat per minute >10 minutes), maternal White blood cells > 15000/mm3 (not justified by the administration of antenatal steroids).
• Cervical dilatation > 3 cm
• Major structural malformations of fetal complications that are related to neurodevelopmental impairment.
• Technical problems to perform an amniocentesis (prediction models include information from amniotic fluid: glucose and IL-6 concentration).

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
EXPERIMENTAL: Intervention; In the intervention arm, the management will be optimized according to the risk of the predictive model. The predictive model of intra-amniotic infection includes maternal C-reactive protein (CRP) (in mg/L) and amniotic fluid glucose (in mg/dL), and the predictive model of spontaneous preterm delivery within 7 days includes gestational age (in weeks), cervical length (in mm), amniotic fluid glucose (in mg/dL) and Interleukin (IL)-6 (in a log10 scale). High risk will be defined when the risk is > 10% in the predictive model of spontaneous delivery in 7 days and > 20% in the predictive model of intra-amniotic infection: If low-risk: we will optimize the standard management reducing the dose of steroids (e.g not administering second doses), tocolysis duration and facilitating discharge home.; If high-risk: we will follow the standard management of each center and we will treat with antibiotics	Drug: Steroid Drug; Steroids doses will be optimized in the intervention group according the risk based on predictive models; Drug: Tocolytic Agents; Tocolysis duration will be optimized in the intervention group according the risk based on predictive models
NO_INTERVENTION: Control; In the control arm the standard management of each center will be followed regarding doses of steroids, duration of tocolysis or maternal stay length duration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antenatal steroid doses	Number of antenatal steroid doses administered	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maternal stay length	Maternal length of hospital stay (in days).	through study completion, an average of 1 year
Clinical chorioamnionitis	Clinical chorioamnionitis occurrence defined by the presence of maternal fever >=38ºC, fetal tachycardia > 160 bpm, leukocytes > 14000/m2 without steroids effect and cervical purulent fluid	through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tocolysis duration	Tocolysis duration (in days)	through study completion, an average of 1 year
Gestational age at delivery	Gestational age at delivery	through study completion, an average of 1 year
Spontaneous delivery within 7 days after admission	Spontaneous delivery within 7 days after admission (yes/no),	through study completion, an average of 1 year
Microbial invasion of amniotic cavity	Microbial invasion of amniotic cavity (yes/no) defined by the presence of a positive amniotic fluid culture, detection of 16S rRNA gene or visualization of microorganisms at the Gram stain	through study completion, an average of 1 year
Cost analyses	Cost analyses: The following resource items will be collected: maternal and neonatal admissions, method of delivery, type of induction, outpatient visits, emergency visits, medication, surgical procedures, maternal stay length.	through study completion, an average of 1 year
Maternal morbidity	Maternal morbidity (yes/no) including intrapartum fever, endometritis, infection of surgical wound, sepsis, curettage, admission to ICU, hysterectomy, need for transfusion, maternal death.	through study completion, an average of 1 year
Neonatal length of hospital stay	Neonatal length of hospital stay (days)	through study completion, an average of 1 year
Neonatal birthweight (in grams)	Neonatal anthropometric measurements	through study completion, an average of 1 year
height (in centimeters)	Neonatal anthropometric measurements	through study completion, an average of 1 year
cephalic, thoracic and abdominal perimeters (in millimeters)	Neonatal anthropometric measurements	through study completion, an average of 1 year
arm circumference (in centimeters)	Neonatal anthropometric measurements	through study completion, an average of 1 year
Adverse neonatal outcome	A composite adverse neonatal outcome (yes/no) defined as the presence or one or more of the following outcomes: fetal or neonatal death, early onset sepsis, moderate/severe bronchopulmonary dysplasia, severe intraventricular haemorrhage, periventricular leukomalacia, surgical necrotizing enterocolitis, retinopathy requiring laser treatment.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Fundacion Clinic per a la Recerca Biomédica
• Collaborators: Germans Trias i Pujol Hospital; Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau; Hospital Universitario 12 de Octubre; Hospital Universitario La Fe; Hospital Universitario La Paz; Hospital Vall d'Hebron; Consorci Sanitari de Terrassa; Hospital Parc Taulí, Sabadell; Hospital Sant Joan de Deu; Hospital Universitario Puerta del Mar; Hospital Clínico Universitario Lozano Blesa; University Hospital Virgen de las Nieves
• Investigators: Principal Investigator: Teresa Cobo, MD, PhD, Fundació Recerca Biomèdica Clínica

Publications and helpful links

General Publications

• Cobo T, Aldecoa V, Figueras F, Herranz A, Ferrero S, Izquierdo M, Murillo C, Amoedo R, Rueda C, Bosch J, Martinez-Portilla RJ, Gratacos E, Palacio M. Development and validation of a multivariable prediction model of spontaneous preterm delivery and microbial invasion of the amniotic cavity in women with preterm labor. Am J Obstet Gynecol. 2020 Sep;223(3):421.e1-421.e14. doi: 10.1016/j.ajog.2020.02.049. Epub 2020 Mar 5.
• Cobo T, Aldecoa V, Bartha JL, Bugatto F, Paz Carrillo-Badillo M, Comas C, Diago-Almeda V, Ferrero S, Goya M, Herraiz I, Marti-Malgosa L, Olivella A, Paules C, Vives A, Figueras F, Palacio M, Gratacos E; OPTIM-PTL group. Assessment of an intervention to optimise antenatal management of women admitted with preterm labour and intact membranes using amniocentesis-based predictive risk models: study protocol for a randomised controlled trial (OPTIM-PTL Study). BMJ Open. 2021 Sep 28;11(9):e054711. doi: 10.1136/bmjopen-2021-054711.

Helpful Links

• Predictive models of spontaneous delivery within 7 days and of intra-amniotic infections description

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 5, 2021
• Primary Completion (ANTICIPATED): September 30, 2023
• Study Completion (ANTICIPATED): December 30, 2023

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (ACTUAL): April 5, 2021

Study Record Updates

• Last Update Posted (ACTUAL): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Premature Birth; Obstetric Labor, Premature; Physiological Effects of Drugs; Reproductive Control Agents; Tocolytic Agents
• Other Study ID Numbers: OPTIM-PTL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all collected IPD
• IPD Sharing Time Frame: Data will be available after the end of the study
• IPD Sharing Access Criteria: https://apps.sjdhospitalbarcelona.org/redcap/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• 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