Rupture of Membranes; PrematurePhase 3PROACT PROMNCT05958953
PeRinatal Outcomes With ACTive Versus Expectant Management of Women With Pre-labor Rupture Of Membranes
A Phase 3 study testing Induction of Labor IoL in people with Rupture of Membranes; Premature and Distress; Fetal, Complicating Delivery, run by University of Modena and Reggio Emilia at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Rupture of Membranes; Premature, Distress; Fetal, Complicating Delivery, Delayed Delivery After Spontaneous or Unspecified Rupture of Membranes
- What is being tested?
- Induction of Labor IoL
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,400 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2023to 12 Nov 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site
AUO Policlinico di Modena
Modena, 41120
Anna Luna Tramontano, MD, 0039 327 0184948, tranalu@iclou.com
Matteo Visconti, MD, 0039 3403502265, matteo.visconti1@gmail.com
About this study
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
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).
Read more
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.
- Conditions
- Rupture of Membranes; Premature, Distress; Fetal, Complicating Delivery, Delayed Delivery After Spontaneous or Unspecified Rupture of Membranes, Maternal Sepsis
- Being tested
- Induction of Labor IoL
- Medical subject headings
- Fetal Membranes, Premature Rupture, Pregnancy Complications, Infectious
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induction of Labor IoLProcedure or surgery
Center-specific IOL protocols, based on international guidelines, will be used.
| Study group | Role | What they receive |
|---|---|---|
| active management | Experimental | early IOL within 8 hours of rupture of membranes. Center-specific IOL protocols will be used. Receives: Procedure: Induction of Labor IoL |
| Expectant management | No intervention | monitoring until 24 hours from rupture of membranes, with subsequent induction of labor (IOL). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: On day 1 or 2 post-partum all relevant delivery and post-partum as well as neonatal variables will be collected.
Secondary outcomes (5)
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.
Measured: On day 1 or 2 post-partum all relevant delivery and post-partum as well as neonatal variables will be collected.
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.
Measured: From day 1 after delivery to the end of the puerperium (42 days after delivery)
use of antibiotics in both mother and newborn as quantity (mg) and quality.
The use of antibiotics will be recorded
Measured: From admission in the Hospital to 42 days after delivery
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.
Measured: From birth to 42 days after delivery
Rate of Pathogen isolation in placenta's speciemen
Placentas and umbilical cord will be collected only in the Milano Buzzi center
Measured: Collection of speciemens immediately after delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2023
- Study startSep 2023 (estimated)
- Primary completionOct 2025 (estimated)
- Study completion12 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rupture of Membranes; PrematureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Modena and Reggio Emilia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Fabio Facchinetti, University of Modena and Reggio Emilia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05958953
- Sponsor's protocol ID
- 2022-002480-30
- Acronym
- PROACT PROM
- Status last verified
- Jul 2023
- First submitted
- 6 Jun 2023
- Last updated
- 25 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05958953
- Acronym / sponsor ID
- PROACT PROM / 2022-002480-30
- Conditions
- Rupture of Membranes; Premature, Distress; Fetal, Complicating Delivery, Delayed Delivery After Spontaneous or Unspecified Rupture of Membranes, Maternal Sepsis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,400 participants (estimated)
- Lead sponsor
- University of Modena and Reggio EmiliaUniversity, hospital or other
- Study start
- Sep 2023 (estimated)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- 12 Nov 2025 (estimated)
- First posted
- 25 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| active management | Experimental | Procedure: Induction of Labor IoLearly IOL within 8 hours of rupture of membranes. Center-specific IOL protocols will be used. |
| Expectant management | No intervention | –monitoring until 24 hours from rupture of membranes, with subsequent induction of labor (IOL). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Induction of Labor IoLCenter-specific IOL protocols, based on international guidelines, will be used. | Procedure or surgery | active management |
Primary outcome
Rate of respiratory support in newborns
Time frame: On day 1 or 2 post-partum all relevant delivery and post-partum as well as neonatal variables will be collected.
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.
5 secondary outcomes
Stillbirth and infection rate
Time frame: On day 1 or 2 post-partum all relevant delivery and post-partum as well as neonatal variables will be collected.
length of hospitalization expressed in days
Time frame: From day 1 after delivery to the end of the puerperium (42 days after delivery)
use of antibiotics in both mother and newborn as quantity (mg) and quality.
Time frame: From admission in the Hospital to 42 days after delivery
neonatal infection as the yield of pathogen from blood or CFS coltures
Time frame: From birth to 42 days after delivery
Rate of Pathogen isolation in placenta's speciemen
Time frame: Collection of speciemens immediately after delivery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Induction of Labor IoL in people with Rupture of Membranes; Premature and Distress; Fetal, Complicating Delivery, run by University of Modena and Reggio Emilia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fabio Facchinetti, Professor (0039 059 4225334, fabio.facchinetti@unimore.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of respiratory support in newborns (time frame: On day 1 or 2 post-partum all relevant delivery and post-partum as well as neonatal variables will be collected.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2023.