Induction of Labor With Oxytocin: When Should Oxytocin be Held?
Condition: Labor Induction; Cesarean Delivery
Study type: Interventional

Summary: 
      The investigators propose to perform a prospective randomized control trial to compare the
      rate of cesarean delivery in women where Oxytocin (OT) is discontinued once active labor
      begins (5 cm dilation) when compared with women where OT is continued at a maintenance level
      per the usual protocol.

      One study group will follow an oxytocin protocol which is incremental until 5 cm dilation and
      then maintained at the same level throughout labor. The second arm will follow an oxytocin
      protocol also incremental, but then discontinued once the cervix is 5 cm. The primary outcome
      will be the rate of cesarean delivery between the groups. Secondary outcomes to be evaluated
      will include duration of the labor, fetal heart rate abnormalities, and frequency of uterine
      hyperstimulation, maternal and neonatal outcomes.

      As mentioned in the study proposal, the proposed experimental arm is currently not performed
      as part of the oxytocin guidelines at the investigators' institution. One study from Israel
      suggests no difference in pregnancy outcomes with the proposed use of oxytocin. Although some
      providers stop the oxytocin in active labor for their patients, this is not a commonly
      performed procedure at the investigators' institution. The investigators are not aware of
      other institutions employing the above practice.
    

Detailed description: 
      Oxytocin is the most common agent used to induce and augment labor. Oxytocin injection is
      approved by the Food and Drug Administration for the initiation or improvement of uterine
      contractions to achieve vaginal delivery. It is used to induce labor and stimulate or
      reinforce labor.

      The relationship of oxytocin and its receptor is crucial in obtaining adequate uterine
      activity and thus inducing active labor. Due to this very balanced relationship, a question
      exists about the optimal regimen of oxytocin administration for induction of labor and on how
      long to continue oxytocin once active labor begins. Some literature suggests that once in the
      active phase of labor oxytocin may be discontinued without altering the progression of labor.
      The objective of this study is to determine whether there is an increased rate of cesarean
      delivery in women undergoing induction of labor when oxytocin is discontinued in the active
      phase of labor.

      Blair-Bell was the first who, in 1909, demonstrated the uterotonic action of posterior
      pituitary extracts at a cesarean delivery. Since then oxytocin, synthesized by du Vigneaud et
      al, has been most commonly used for the induction of labor. Oxytocin (OT) is a polypeptide
      hormone, synthesized in the hypothalamus and in reproductive tissues during pregnancy.

      Oxytocin stimulates uterine contraction by mechanisms involving the activation of
      receptor-operated calcium channels. Calcium-dependent phosphorylation of myosin triggers the
      interaction of myosin and actin subunits throughout the uterus leading to contractions.

      During labor and parturition the relationship between oxytocin and its receptor is critical
      in achieving adequate uterine contractions and thus active labor. If few receptors are
      present, as seen in an early gestation, a large amount of OT is required for contractions.
      The opposite is true in term pregnancy. OT binding to its receptor is very important because
      excess doses of OT are not productive and may have undesirable effects.

      The use of OT can cause hyperstimulation (excessive contractions leading to abnormal fetal
      heart rate patterns) even when used in adequate doses. Nonetheless, induction of labor with
      OT can be beneficial in reducing the incidence of prolonged labor and subsequent cesarean
      delivery without increasing perinatal morbidity or mortality.

      Currently OT protocols vary throughout hospitals. Both low and high dose regimens as outlined
      by the American College of Obstetrician and Gynecologists are appropriate for labor
      induction. At our facility intravenous OT is started at 1-2 milliunits per minute and
      increased by 2 milliunits every 15 minutes until obtaining normal progression of labor
      usually at 150-300 Montevideo units on the contraction monitor. Low dose regimens with less
      frequent increases in dose are associated with decreased hyperstimulation. However use of
      high-dose oxytocin has not been found to increase the incidence of birth asphyxia or
      perinatal morbidity.

      As mentioned in the study proposal, the proposed experimental arm is currently not performed
      as patient of the oxytocin guidelines at our institution. One study from Israel found no
      difference in pregnancy outcomes with the proposed use of oxytocin. Although we are aware of
      one provider that stops the oxytocin drip once the patient is in active labor, this is not a
      commonly performed procedure at our institution. We are not aware of other institutions
      employing the above.

      We propose to perform a prospective randomized control trial to compare the rate of cesarean
      delivery in women where OT is discontinued once active labor begins (5 cm dilation) when
      compared with women where OT is continued at a maintenance level per the usual protocol.

      One study group will follow an oxytocin protocol which is incremental until 5 cm dilation and
      then maintained at the same level throughout labor. The second arm will follow an oxytocin
      protocol also incremental, but then discontinued once the cervix is 5cm. The primary outcome
      will be the rate of cesarean delivery between the groups. Groups will be stratified by parity
      (nulliparous vs. multiparous). Secondary outcomes to be evaluated will include duration of
      the labor, fetal heart rate abnormalities, and frequency of uterine hyperstimulation,
      maternal and neonatal outcomes.

      Based on our sample size calculation, we will need at least 160 patients in each arm of the
      study to find an increase in the cesarean delivery rate from 25% to 40% in women who undergo
      induction of labor where oxytocin is discontinued once the active phase of labor begins. This
      sample size calculation uses a power of 80% and an alpha level (statistical significance) of
      0.05. The baseline rate of cesarean in the US is 25-30%. We chose 40% as a significantly
      increased rate of CS since this rate would represent a 60% increase in CS from the baseline
      risk in the population.

      We are looking for a difference in cesarean rates between the experimental arm and the
      maintenance arm. Evaluating the data as an equivalence study (no difference between the
      interventions) would significantly increase the sample size needed for the study. With our
      current sample size calculation, if a cesarean rate difference is not found between the
      groups (meaning discontinuation of oxytocin is not inferior to the maintenance use of
      oxytocin in active labor), we can state that our data do not support a significant increase
      (60% increase) in the risk of cesarean delivery rate when reducing the amount of oxytocin
      used for induction of labor.

      It is not possible to blind the providers, nurses or patients to the arm of the study since
      oxytocin infusions need to be titrated and dosing level is important in managing labor. This
      will be an intention to treat analysis.

      The decision to perform a cesarean delivery will be according to standard obstetric
      indications and will be ultimately decided by the treating physician, regardless of treatment
      assignment. Obstetric criteria are in place to perform cesarean deliveries. The treating
      physician at any time may restart the oxytocin in patients originally assigned to the
      oxytocin discontinuation arm.
    

Intervention name(s): Oxytocin; Oxytocin discontinuation
Intervention type(s): Drug; Drug
Intervention description(s): Continuation of oxytocin once in active labor; Oxytocin will be stopped once in active labor
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Induction of labor in term pregnancies; Term pregnancy; Cesarean delivery