Routine Early vs Delayed Amniotomy for Preterm Pregnancies: A Randomized Open Label Trial

Study Overview
=================
Brief Summary
-----------------
To compare the duration of preterm induction of labor in women undergoing early vs. late or no artificial rupture of membranes (AROM). Maternal and neonatal outcomes will also be compared between the two groups.

Detailed Description
-----------------
Women presenting with a preterm singleton pregnancy between 28.0 and 36.6 weeks of gestation with cephalic lie and a medical indication for induction of labor will be approached for this study. The patient/provider must be attempting induction with the goal of vaginal delivery. Women with ruptured membranes, suspected intrauterine infection, prior uterine scar, fetal demise, or a fetal anomaly will be excluded. Women that agree to the study will be randomized to 2 groups: the early amniotomy group and the late amniotomy group. Women in the early amniotomy group will undergo artificial rupture of membranes (AROM) prior to reaching cervical dilation of 4 cm. Women in the late amniotomy group may not undergo AROM until they reach cervical dilation of greater than 4 cm or they have been on an oxytocin drip for greater than 10 hours with no cervical change. It is possible that a woman in the late amniotomy group will not undergo AROM at all. The primary outcome under consideration is time in labor. Secondary outcomes include rates of chorioamnionitis, postpartum endometritis, mode of delivery, and neonatal outcomes.

Official Title
-----------------
Comparative Effectiveness of Routine Early Versus Delayed Amniotomy for Pregnancies Less Than 37 Weeks Gestational Age: A Randomized Open Label Trial (CEREAL)

Conditions
-----------------
Labor, Premature

Intervention / Treatment
-----------------
* Procedure: Early Artificial rupture of membranes
* Procedure: Delayed Artificial rupture of membranes


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Preterm singleton pregnancy between 28.0 and 36.6 completed weeks of gestation Fetus in the cephalic position Intent to induce labor for vaginal delivery If cervical ripening is planned, patient must be enrolled within an hour of initiation of ripening. If no ripening is planned, enrollment must be complete prior to starting induction. Exclusion Criteria: Preterm premature rupture of membranes (PPROM) Fever or suspected chorioamnionitis prior to start of IOL Prior uterine scar Infection with HIV/Hepatitis B Virus (HBV)/Hepatitis C Virus (HCV) or an active Herpes Simplex Virus (HSV) infection Intrauterine fetal demise Major fetal anomaly Cervical dilation > 4 cm
Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early artificial rupture of membranes<br>Women in this arm will undergo artificial rupture of membranes before 4 cm of cervical dilation is reached during induction of labor as long as the procedure is deemed clinically safe and feasible. | Procedure: Early Artificial rupture of membranes<br>* Women in this arm will undergo artificial rupture of membranes before 4 cm of cervical dilation is reached during induction of labor as long as the procedure is deemed clinically safe and feasible.<br>|
| Active Comparator: Delayed artificial rupture of membranes<br>Women in this arm may undergo artificial rupture of membranes performed only after 4 cm of cervical dilation is reached during induction of labor. Rupture may also be performed after 10 hours of oxytocin administration with no cervical change. | Procedure: Delayed Artificial rupture of membranes<br>* Women in this arm may undergo artificial rupture of membranes performed only after 4 cm of cervical dilation is reached during induction of labor. Rupture may also be performed after 10 hours of oxytocin administration with no cervical change.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total duration of labor. | The duration of labor begins with administration of the first induction agent (i.e. Cook balloon, Foley catheter, prostaglandins, or oxytocin) and ends with delivery. | Induction of labor until delivery (1 hr - 48 hrs) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Labor Outcomes:Time from completion of cervical ripening to delivery | When the last induction agent is a foley/Cook balloon, or cervidil (dinoprostone), completion of cervical ripening will be defined as the time when the agent is removed. When the last induction agent is misoprostol, completion of cervical ripening will be defined as 4 hours after administration of the last dose. | Induction of labor until delivery (1 hr - 48 hrs) | 
| Labor Outcomes: Delivery before 24 hours from start of Induction of Labor (IOL) | A dichotomization of duration of labor | Induction of labor until delivery (1 hr - 48 hrs) | 
| Labor Outcomes: Duration of the 2nd stage of labor | Defined as time from the first cervical exam with complete dilation and effacement to the time of delivery | Induction of labor until delivery (1 hr - 48 hrs) | 
| Maternal Outcome:Cesarean delivery | Mode of delivery | at delivery | 
| Maternal/Labor Outcomes: Indication for Cesarean delivery | Reason for cesarean delivery | at delivery | 
| Maternal/Labor Outcomes:Operative vaginal delivery | Use of either a vacuum device or obstetrical forceps | at delivery | 
| Maternal intrapartum fever or chorioamnionitis | Defined as persistent intrapartum fever and/or suspected or confirmed intraamniotic infection (20) | during labor to delivery | 
| Post-partum endometritis: | defined as postpartum febrile morbidity in the absence of another causative factor (i.e. wound infection, deep venous thrombosis). Postpartum febrile morbidity is defined as oral temperature ≥ 38.0⁰ C on any 2 of the first 10 days postpartum, exclusive of the first postpartum day | up to 10 days | 
| Epidural anesthesia | Use of epidural regional anesthesia for pain control during induction of labor | during labor | 
| Recurrent variable or late decelerations | As defined by The American College of Obstetrics and Gynecology ( ACOG), practice bulletin No 110 | during labor | 
| Meconium stained amniotic fluid | Meconium is noted in the amniotic fluid after rupture of membranes | during labor and delivery | 
| Tachysystole | As defined by ACOG, practice bulletin No 110 | during labor | 
| Use of amnioinfusion | Placement of an intrauterine catheter and infusion of saline into the uterus during induction of labor | during labor | 
| Use of intrapartum tocolytics | Administration of a tocolytic drug during labor | during labor | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pregnancy, labor induction, preterm