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PeRinatal Outcomes With ACTive Versus Expectant Management of Women With Pre-labor Rupture Of Membranes (PROACT PROM)

Primary Purpose

Rupture of Membranes; Premature, Distress; Fetal, Complicating Delivery, Delayed Delivery After Spontaneous or Unspecified Rupture of Membranes

Status
Not yet recruiting
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Induction of Labor IoL
Sponsored by
University of Modena and Reggio Emilia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Rupture of Membranes; Premature

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Age ≥18 years of age at the time of randomization Gestational age ≥ 37 weeks Negative rectovaginal GBS swab Absent/poor uterine contractile activity 6 h after PROM (0-2 contractions /10 min) Cephalic presentation Ability to provide an informed consent Signed informed consent Exclusion Criteria: Prematurity (<37 weeks) GBS positive vagino-rectal swab or with an unknown swab Multiple pregnancies Previous cesarean section (CS) Breech presentation, transverse lie or other indication for elective CS Suspected clinic for intra-amniotic infection (According to the Triple I criteria) Stained amniotic fluid Alterations of the FHR Unknown exact ROM time Known hypersensitivity to drugs for IOL or their excipients Presence of unknown vaginal bleeding Presence of maternal kidney disease (GFR <15 ml/min/1,73 m2). Every condition contraindicating vaginal delivery

Sites / Locations

  • AUO Policlinico di Modena

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

active management

Expectant management

Arm Description

early IOL within 8 hours of rupture of membranes. Center-specific IOL protocols will be used.

monitoring until 24 hours from rupture of membranes, with subsequent induction of labor (IOL).

Outcomes

Primary Outcome Measures

Rate of respiratory support in newborns
The primary objective of this study is to evaluate whether active management of women with PROM (early induction) reduces the newborn need of respiratory support, collecting data on Apgar score, neonatal blood gas analysis and the rate of respiratory distress after birth and rate of respiratory support divided by type. The need for neonatal ventilatory support will be evaluated at delivery and include at least one of the following measures: free flowing oxygen in incubator, low flow oxygen (<2 LPM), high flow oxygen (>3 LPM), NCPAP or other NIV, mechanical ventilation.

Secondary Outcome Measures

Stillbirth and infection rate
This secondary objectives of this study are related to the safety of the active management assessed through the rate of stillbirths, the onset of infections in the mother and fetus and through the length of hospitalization of the dyads. Moreover, another objective is to reduce the use of antibiotic treatments (ATB) in both mothers and newborns.
length of hospitalization expressed in days
The lenght of hospitalization and the need for re-hospitalizations are related to the safety of the active management assessed through the rate of stillbirths, the onset of infections in the mother and fetus and through the length of hospitalization of the dyads. Moreover, another objective is to reduce the use of antibiotic treatments (ATB) in both mothers and newborns.
use of antibiotics in both mother and newborn as quantity (mg) and quality.
The use of antibiotics will be recorded
neonatal infection as the yield of pathogen from blood or CFS coltures
Suspected infection is based on the presence of clinical symptoms (neonatal tachycardia, hyperpyrexia, alteration of the skin color) and abnormal laboratory markers, i.e. an increase in C reactive proteins above 1.5 mg/dl.
Rate of Pathogen isolation in placenta's speciemen
Placentas and umbilical cord will be collected only in the Milano Buzzi center

Full Information

First Posted
June 6, 2023
Last Updated
July 14, 2023
Sponsor
University of Modena and Reggio Emilia
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1. Study Identification

Unique Protocol Identification Number
NCT05958953
Brief Title
PeRinatal Outcomes With ACTive Versus Expectant Management of Women With Pre-labor Rupture Of Membranes
Acronym
PROACT PROM
Official Title
PeRinatal Outcomes With ACTive Versus Expectant Management of Women With Pre-labor Rupture Of Membranes: a Phase III, Open-label, Randomized Controlled Multicentric Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
November 12, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Modena and Reggio Emilia

4. Oversight

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

5. Study Description

Brief Summary
Term pre-labor rupture of membranes (PROM) occurs in about 12% of pregnancies and the time between PROM and delivery increases the risk of maternal/fetal infections. However, conflicting results are reported by studies investigating risks and benefits of expectant management versus induction of labor (IOL). Expectant management was associated with maternal and fetal infectious complications and subsequent increased risk of maternal and neonatal morbidity. Studies suggest that the increase in infectious risk for both is proportional to the increase in the time interval between the ROM and the birth, others reject this assumption. In PeRinatal Outcomes With ACTive Versus Expectant Management of Women With Pre-labor Rupture Of Membranes (PROACTIVE PROM) on admission, PROM will be diagnosed. After 6 hours from the rupture of membranes, the woman will then be assessed for eligibility. A 1:1 randomization will follow within two hours (6-8 hours from PROM) in two distinct arms: 1) Expectant management 2) Active menagement (early IOL within 8 hours of rupture of membranes). The first objective of this study is to evaluate whether active management of women with PROM (early induction) reduces the newborn need of respiratory support. The secondary objectives of this study are related to the safety of the active management assessed through the rate of stillbirths, the onset of infections in both mother and fetus and the length of hospitalization of the dyads. Moreover, another objective is to reduce the use of antibiotic treatments (ATB) in both mothers and newborns. The rationale of this study is that reducing the time between the PROM and delivery through an early IOL will reduce the adverse maternal and neonatal outcomes. The hypothesis underneath this trial comes from a preliminary retrospective cohort study conducted in Modena, which included 2689 mother-neonates dyads from singleton pregnant women at term. In deliveries of ROM >24 hours significantly more neonates required ventilatory support than those born within 24 hours, although no significant differences were found regarding overt infections. According to the Cochrane database, expectant management of PROM is associated with maternal and fetal infectious complications and subsequent increased risk of maternal and neonatal morbidity together with an increased risk of ATB use. The increase of infectious risk is proportional to the time elapsed since the rupture of the membranes (ROM) and birth. However, unpublished data from our group suggest that respiratory distress requiring interventions may be frequently caused by intrinsic inflammatory-related effects of prolonged ROM rather than infection; this is suggested by an increase of C-reactive protein levels in neonates with mild respiratory signs untreated with antibiotics. In addition, in a survey performed in our country expectant management increased intrapartum antibiotic prophylaxis (IAP), although not strictly indicated by the most current guidelines. On the light of these data, it appears reasonable to promote induction of labor, to prevent complication caused not only by the infectious risk mentioned above, but also respiratory distress, probably associated to a neonatal maladaptation, in non-infectious newborns. On the other hand, it should also be considered that 75% of women enter labor spontaneously within 24 hours from PROM and induction of labor (IOL) might not be needed in such cases.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rupture of Membranes; Premature, Distress; Fetal, Complicating Delivery, Delayed Delivery After Spontaneous or Unspecified Rupture of Membranes, Maternal Sepsis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
active management
Arm Type
Experimental
Arm Description
early IOL within 8 hours of rupture of membranes. Center-specific IOL protocols will be used.
Arm Title
Expectant management
Arm Type
No Intervention
Arm Description
monitoring until 24 hours from rupture of membranes, with subsequent induction of labor (IOL).
Intervention Type
Procedure
Intervention Name(s)
Induction of Labor IoL
Intervention Description
Center-specific IOL protocols, based on international guidelines, will be used.
Primary Outcome Measure Information:
Title
Rate of respiratory support in newborns
Description
The primary objective of this study is to evaluate whether active management of women with PROM (early induction) reduces the newborn need of respiratory support, collecting data on Apgar score, neonatal blood gas analysis and the rate of respiratory distress after birth and rate of respiratory support divided by type. The need for neonatal ventilatory support will be evaluated at delivery and include at least one of the following measures: free flowing oxygen in incubator, low flow oxygen (<2 LPM), high flow oxygen (>3 LPM), NCPAP or other NIV, mechanical ventilation.
Time Frame
On day 1 or 2 post-partum all relevant delivery and post-partum as well as neonatal variables will be collected.
Secondary Outcome Measure Information:
Title
Stillbirth and infection rate
Description
This secondary objectives of this study are related to the safety of the active management assessed through the rate of stillbirths, the onset of infections in the mother and fetus and through the length of hospitalization of the dyads. Moreover, another objective is to reduce the use of antibiotic treatments (ATB) in both mothers and newborns.
Time Frame
On day 1 or 2 post-partum all relevant delivery and post-partum as well as neonatal variables will be collected.
Title
length of hospitalization expressed in days
Description
The lenght of hospitalization and the need for re-hospitalizations are related to the safety of the active management assessed through the rate of stillbirths, the onset of infections in the mother and fetus and through the length of hospitalization of the dyads. Moreover, another objective is to reduce the use of antibiotic treatments (ATB) in both mothers and newborns.
Time Frame
From day 1 after delivery to the end of the puerperium (42 days after delivery)
Title
use of antibiotics in both mother and newborn as quantity (mg) and quality.
Description
The use of antibiotics will be recorded
Time Frame
From admission in the Hospital to 42 days after delivery
Title
neonatal infection as the yield of pathogen from blood or CFS coltures
Description
Suspected infection is based on the presence of clinical symptoms (neonatal tachycardia, hyperpyrexia, alteration of the skin color) and abnormal laboratory markers, i.e. an increase in C reactive proteins above 1.5 mg/dl.
Time Frame
From birth to 42 days after delivery
Title
Rate of Pathogen isolation in placenta's speciemen
Description
Placentas and umbilical cord will be collected only in the Milano Buzzi center
Time Frame
Collection of speciemens immediately after delivery

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years of age at the time of randomization Gestational age ≥ 37 weeks Negative rectovaginal GBS swab Absent/poor uterine contractile activity 6 h after PROM (0-2 contractions /10 min) Cephalic presentation Ability to provide an informed consent Signed informed consent Exclusion Criteria: Prematurity (<37 weeks) GBS positive vagino-rectal swab or with an unknown swab Multiple pregnancies Previous cesarean section (CS) Breech presentation, transverse lie or other indication for elective CS Suspected clinic for intra-amniotic infection (According to the Triple I criteria) Stained amniotic fluid Alterations of the FHR Unknown exact ROM time Known hypersensitivity to drugs for IOL or their excipients Presence of unknown vaginal bleeding Presence of maternal kidney disease (GFR <15 ml/min/1,73 m2). Every condition contraindicating vaginal delivery
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fabio Facchinetti, Professor
Phone
0039 059 4225334
Email
fabio.facchinetti@unimore.it
Facility Information:
Facility Name
AUO Policlinico di Modena
City
Modena
ZIP/Postal Code
41120
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Luna Tramontano, MD
Phone
0039 327 0184948
Email
tranalu@iclou.com
First Name & Middle Initial & Last Name & Degree
Matteo Visconti, MD
Phone
0039 3403502265
Email
matteo.visconti1@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

PeRinatal Outcomes With ACTive Versus Expectant Management of Women With Pre-labor Rupture Of Membranes

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