Mifepristone and Mid-Trimester Termination of Pregnancy
Condition: Abortion, Induced; Abortion, Second Trimester
Study type: Interventional

Summary: 
      Mid-second trimester medical terminations of pregnancy require admission to the hospital for
      the length of time it takes a woman to abort. The current protocol at BMC uses intra-amniotic
      digoxin injection the day prior to admission. The following day, the woman is admitted and
      given sequential doses of misoprostol until delivery occurs. The average length of time
      between the first dose of misoprostol and delivery is 12 hours, requiring most women to stay
      overnight. This is a randomized, placebo-controlled, double-blinded study designed to
      determine whether adding mifepristone significantly reduces the induction interval time (time
      between starting the first misoprostol and delivery) required for a second trimester
      termination.
    

Detailed description: 
      This is a randomized, placebo-controlled, double-blinded study.

      Allocation Method: Women will be randomized using a computer-run random number table. Tablets
      will be placed in capsules by the pharmacy according to the randomization chart.

      Blinding: Subjects will receive a capsule containing either 200 mg of mifepristone or 250 mg
      Vitamin C. Neither she nor the researcher will be aware of which medication she receives.

      Outcomes: The primary outcome measured will be the mean interval from first misoprostol dose
      to fetal expulsion. Secondary outcomes include the proportion of women delivering within 24
      hours from the first dose of misoprostol and the proportion of women with a complete delivery
      not requiring additional treatment for retained placenta. We will also compare the amount of
      pain medication used, as well as the length of hospital stay between the two groups.

      Inclusion criteria Inclusion criteria: · Need for second trimester induction for termination
      of pregnancy · Gestational age of 18-23 weeks · At least 18 years of age or 16 years old with
      parental consent No medical contraindication to the use of digoxin and misoprostol for the
      purposes of inducing abortion. · Able and willing to give informed consent in English or
      Spanish

      Exclusion criteria Exclusion criteria: · Known allergy to mifepristone, misoprostol or
      prostaglandins · Pre-existing intrauterine fetal demise · Premature preterm rupture of
      membranes · IUD in place · History of chronic adrenal failure, porphyrias; or concurrent
      long-term corticosteroid treatment Unable or unwilling to give informed consent in English or
      Spanish

      Involvement in the study will be as follows: on study day number one, all patients undergo an
      ultrasound-guided amniocentesis with intra-amniotic injection of digoxin regardless of entry
      into the study. Study patients will be randomized to the treatment or placebo group, and will
      receive one of two similar-looking tablets containing the allocated medication. The tablet
      will be swallowed in the clinic. The patient, researchers and the care providers will be
      blinded to group assignment. All patients return to the hospital the the day after their
      digoxin injection for induction. From this point on, the treatment of women enrolled and
      those not enrolled in the study will be identical; they are admitted to the hospital and
      induction for termination is begun using an initial 400mcg of misoprostol buccally. The
      initial dose is followed by 200 mcg of misoprostol every six hours until delivery is
      successful or 24 hours passes without delivery. Less than 5% of women require more than 24
      hours of induction, and approximately 15% require extraction of the placenta if it does not
      pass spontaneously after the fetus. The subjects enrolled will not differ from other
      termination patients in regards to the following: 1. the number of appointments or time
      required in the hospital 2. use of intra-amniotic digoxin 3. termination method; misoprostol,
      400 mg, followed by 200 mg every 6 hours 4. pain medication administration (PCA narcotics) 5.
      Medical evaluation of need to use other methods of completing abortion if 24 hours has
      elapsed after first misoprostol dose without delivery.

      Analytic Plan:

      The primary outcome is the length of induction interval for termination. The Kaplan-Meier
      procedure will be utilized to create a survival curve for analysis of induction to delivery
      interval by time. Demographic data for each group will also be compared to assure that there
      are no other differences between groups. Chi -square analysis will be used for dichotomous
      variables and t-tests for continuous variables.Study Size and Power:

      A power calculation was performed for time from induction to delivery using a significant
      value of 0.05 and power of 80% using a survival analysis power formula. We used our previous
      data to estimate the mean time of induction and then estimated a likely delta (difference
      between the two treatment groups) of 35%. The number of patients needed in each group using
      this calculation is 32, and therefore the total number needed is 64.
    

Intervention name(s): Addition of mifepristone 200 mg 24 hours before induction
Intervention type(s): Drug
Intervention MeSH terms: Mifepristone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: mifepristone; induction; abortion; injection, intra-amniotic