Preterm Induction of Labor Timing of Amniotomy: A Randomized Controlled Trial

Study Overview
=================
Brief Summary
-----------------
Artificial rupture of membranes (amniotomy) is a commonly used technique to safely induce and augment labor. It has been shown to reduce the duration of spontaneous and induced labor in term patients (≥37 weeks' gestation). The utility of amniotomy in preterm patients (<37 weeks' gestation) undergoing medically-indicated induction of labor is unknown. However, it remains a commonly used strategy. We will conduct a trial comparing early amniotomy versus late amniotomy during medically-indicated induction of labor between 23.0 and 35.6 weeks gestation. Women will be randomized to early or late amniotomy after the obstetrician has decided to induce labor for a medical indication. We hypothesize that more women in the early amniotomy group will require cesarean delivery, and the duration of labor will increase in the early amniotomy group.

Detailed Description
-----------------
The rate of preterm birth in the United States is nearly 10%. Up to one-third of these births are the result of a medically-indicated delivery. While induction of labor in women at term gestation has been extensively studied, the same is not true for preterm gestations. Consequently, the same methods of labor induction are used in term and preterm gestations, although preterm gestations may have different responses to induction agents compared to term gestations. At our institution, a standard induction of labor - for term or preterm women - is performed using a cervical Foley catheter or misoprostol for cervical ripening with the addition of intravenous oxytocin for labor augmentation. As membranes do not typically spontaneously rupture during the induction process, amniotomy is commonly utilized by providers to help augment labor. Amniotomy releases prostaglandin-rich amniotic fluid. These prostaglandins are important mediators of uterine contractility and ultimately active labor. It has been shown to reduce the duration of spontaneous and induced labor in term patients. The timing of amniotomy is left up to the discretion of the treating providers, as there are no randomized controlled trials to support early versus late amniotomy at preterm gestations. However, a retrospective cohort of nulliparous and multiparous women at our institution undergoing induction at 23-34 weeks, and evaluating early amniotomy at <4cm cervical dilation versus late amniotomy at ≥4cm dilation, showed an increased risk of cesarean delivery and increased time from start of induction to delivery for early amniotomy, although only the cesarean delivery outcome was significant after adjusting for confounders. We will conduct an intention-to-treat randomized controlled trial comparing early amniotomy versus late amniotomy during medically-indicated induction of labor between 23.0 and 35.6 weeks gestation. Women will be randomized to early or late amniotomy after the attending obstetrician has decided to induce labor for a medical indication. Early amniotomy will be performed prior to 4cm cervical dilation being reached. Late amniotomy will be performed at greater than or equal to 4cm cervical dilation. The purpose of this study is to determine whether timing of amniotomy during medically-indicated preterm induction of labor affects labor outcomes. We will specifically be looking at risk of cesarean delivery, duration of labor, maternal morbidity, and neonatal morbidity. We hypothesize that more women in the early amniotomy group will require cesarean delivery and that the duration of labor will increase in the early amniotomy group.

Official Title
-----------------
Preterm Induction of Labor Timing of Amniotomy: A Randomized Controlled Trial

Conditions
-----------------
Preterm Pregnancy, Labor Induction

Intervention / Treatment
-----------------
* Procedure: Early Amniotomy
* Procedure: Late Amniotomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Singleton gestation Gestational age at randomization between 23.0 and 35.6 weeks Induction of labor planned for maternal or fetal indications Reassuring fetal status Vertex presentation Exclusion Criteria: Plan for cesarean delivery or contraindication to labor Cervix ≥4cm dilated at start of induction Signs of spontaneous labor (active contractions with cervical change) Ruptured membranes Chorioamnionitis Intrauterine fetal demise Known major fetal anomaly Participation in any other clinical trial involving the course of labor Maternal hepatitis B, C, or HIV infection (or unknown status) Deferring intrapartum fetal monitoring and/or cesarean section for any reason (for example, after periviability counseling)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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
Interventional Model Description: Participants are assigned to early amniotomy (<4cm cervical dilation) or late amniotomy (≥4cm dilated). Participants may crossover due due to clinical conditions that are not preventable. These conditions may include: unengaged vertex at time of attempted amniotomy, need for internal monitors, or cervical dilation that does not reach 4cm.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early amniotomy<br>Women randomized to early amniotomy will have their membranes ruptured in usual fashion using an amniotomy hook when the cervix is less than 4cm dilated. This will occur after cervical ripening has taken place, with 1) a cervical Foley balloon catheter with or without oxytocin and/or 2) misoprostol. Prior to amniotomy, the obstetric provider will assess whether or not the fetal head is engaged. If the fetal head is not engaged (applied to the cervix), amniotomy will be deferred. The patient will be examined every 2 hours until amniotomy can be safely performed (in keeping with our institutional standard of care to examine women every 2-4 hours in labor). | Procedure: Early Amniotomy<br>* This intervention involves using an amniotomy hook to rupture the membranes during a sterile vaginal exam. This intervention will be performed prior to the cervix being dilated 4cm.<br>|
| Experimental: Late amniotomy<br>Women randomized to late amniotomy will have their membranes ruptured once the cervix reaches at least 4cm dilation. This will occur after cervical ripening has taken place, with 1) a cervical Foley balloon catheter with or without oxytocin and/or 2) misoprostol. If the cervix fails to reach 4cm dilation 12 hours following cervical ripening, amniotomy will be performed. | Procedure: Late Amniotomy<br>* This intervention involves using an amniotomy hook to rupture the membranes during a sterile vaginal exam. This intervention will be performed once the cervix is at least 4cm dilated.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cesarean delivery | Proportion of women requiring cesarean delivery | Duration is dependent upon the length of labor. The maximum time frame would be anticipated to be 120 hours from start of the induction. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interval from induction onset to delivery | Time (hours) from the start of induction (initiation of first cervical ripening agent) to delivery (vaginal or cesarean) | Duration is dependent upon the length of labor. The maximum time frame would be anticipated to be 120 hours from start of the induction. | 
| Interval from induction onset to vaginal delivery | Time (hours) from the start of induction (initiation of first cervical ripening agent) to vaginal delivery only | Duration is dependent upon the length of labor. The maximum time frame would be anticipated to be 120 hours from start of the induction. | 
| Composite maternal morbidity | Composed of seven outcomes: chorioamnionitis (defined as maternal fever >100.3 plus maternal tachycardia, fetal tachycardia, purulent amniotic fluid, or fundal tenderness prior to delivery) endometritis (defined as maternal fever >100.3 at least 12 hours after delivery with fundal tenderness or purulent discharge) surgical site infection (infection within 30 days at the surgical site including superficial, deep, organ/space infections) pneumonia (radiologic diagnosis of pneumonia accompanied by clinical signs/symptoms) urinary tract infection (>100,000 colonies of a single species in urine culture accompanied by clinical signs/symptoms) postpartum hemorrhage (estimated blood loss >1000 mL) umbilical cord prolapse | Measured from start of induction of labor up to 42 days following delivery | 
| Composite neonatal morbidity | Composed of five outcomes: perinatal death (death of a fetus during labor or within 28 days of life) neonatal sepsis (critically ill infant in whom systemic infection is suspected with a positive blood, cerebrospinal fluid (CSF), or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal X-ray confirming infection) intraventricular hemorrhage (confirmed on ultrasound or MRI) cord blood acidemia (umbilical artery gas pH <= 7.0 or base excess >= 12) Apgar <5 at 5 minutes | Measured up to 28 days of life for the newborn | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Labor induction, Cesarean delivery, Preterm labor induction, Duration of labor induction