Induction With Misoprostol: Oral Mucosa Versus Vaginal Epithelium (IMPROVE)

Pregnancy Clinical Trial

— IMPROVE  

Official title:

Induction With Misoprostol: Oral Mucosa Versus Vaginal Epithelium

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02408315
• Other study ID #: IMPROVE
• Status: Completed
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: December 2021

Study information

• Verified date: March 2022
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to compare the efficacy and safety of vaginal and buccal misoprostol for women undergoing labor induction at greater than or equal to 37+ 0 completed weeks gestation. Thus, the investigators have both efficacy and a safety primary outcomes.

The secondary objective of this study is to assess the pharmacokinetic(PK) parameters with these two routes of administration in a sub-cohort of this trial. The long term objective of this line of research is to inform providers' clinical decision making for the large number of women having labor induction. By providing robust PK and pharmacodynamic (PD) evaluation, clinical outcomes data for these two routes of administration, clinicians will be informed for evidence-based decisions about the preferred route of administration of misoprostol.

Description:

Misoprostol is currently administered in many different ways. It can be administered vaginally, rectally, orally, buccally, and sublingually. Each route has its benefits and potential drawbacks. While vaginal administration is most common, recent trends in practice have yielded more buccal use of this drug. There is extensive clinical experience with this agent and a large body of published reports supporting its safety and efficacy when used appropriately. However, we only found one published trial directly comparing buccal to vaginal misoprostol head-to-head. In that trial, there were no significant differences in any of the outcomes other than higher rates of tachysystole in the buccal group. However, this trial utilized higher doses of misoprostol (up to 100mcg) than are typically used clinically per the ACOG Practice Bulletin (starting at 25 mcg).

Additionally, there are few comparisons of the pharmacokinetics of misoprostol between the buccal and vaginal routes. In fact, all of the PK studies comparing these routes are in women undergoing pregnancy terminations in the 1st or 2nd trimesters and do not include women undergoing labor induction at term. As the physiological changes in pregnancy have a profound impact on drug metabolism and disposition, this is an important gap in the current knowledge.

The 3 Specific Aims of this trial are:

1. To compare the efficacy and safety of 25 mcg of misoprostol initially followed by 50mcg thereafter administered by either buccal or vaginal route in a placebo-controlled, double blind RCT. We will recruit women at term undergoing labor induction to accomplish this trial.

2. To compare the PK parameters of 25 mcg and 50 mcg of misoprostol administered by either buccal or vaginal routes. Further, we will analyze the clinical outcomes in Aim 1 based on the PK parameters, controlling for patient characteristics, to assess the impact of PK parameters on clinical success of this drug. In this way, we hope to comment on the strategic dose and individualized dosing model potential for labor induction with misoprostol.

3. To compare the trial participant satisfaction with each route of administration to improve patient-based outcomes. This will be done by administering a satisfaction survey at the end of the trial. As participants will have study drug placed both buccally and vaginally, they will be uniquely able to comment on comfort and preference for route of delivery.

We will recruit women who are admitted for term labor induction and for whom the provider plans to utilize misoprostol. Women will be randomized to receive either buccal or vaginal misoprostol; first dose will be 25 mcg followed by 50mcg for subsequent doses. Three hundred women will be recruited to the overall trial and a subcohort of 60 women will be recruited to participate in the PK portion of the trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: December 2021
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 14 Years to 45 Years

Eligibility

Inclusion Criteria:

• A medical indication for induction of labor at a gestational age between 37 +0 and 38 +6 weeks OR an elective or medical indication for induction of labor at a gestational age greater than or equal to 39 + 0 completed weeks

• Participant age of greater than or equal to14 years old

• Singleton pregnancy

• Modified Bishop score of less than or equal to 6

• Vertex fetal presentation by examination or ultrasound

• Any membrane status

Exclusion Criteria:

• Elective inductions between 37 +0 and 38 +6 completed weeks are specifically excluded

• Known intrauterine fetal demise

• Any uterine scar including prior cesarean section and myomectomy

• Known major fetal congenital malformations that may impact neonatal health

• Other evidence of fetal compromise (such as Category 2 or 3 tracing) before the induction begins

• Prior induction/cervical ripening methods utilized during this pregnancy

• Allergy to misoprostol

• Known untreated cervical infection (e.g. Gonorrhea, Chlamydia)

• Planned cesarean section due to maternal or fetal condition

• Any other contraindication to labor induction or misoprostol therapy

Related Conditions & MeSH terms

• Pregnancy

Intervention

Drug:
• misoprostol/placebo
buccal or vaginal routes of administration/ placebo to compare methods for efficacy and safety during induction.

Locations

Country	Name	City	State
United States	IU Health Methodist Hospital	Indianapolis	Indiana
United States	Sidney and Lois Eskenazi Hospital	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Nassar AH, Awwad J, Khalil AM, Abu-Musa A, Mehio G, Usta IM. A randomised comparison of patient satisfaction with vaginal and sublingual misoprostol for induction of labour at term. BJOG. 2007 Oct;114(10):1215-21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetic Profiling of Misoprostol	pharmacokinetic parameters (Area under the curve, half-life, maximum concentration) measured over first 2 study drug doses	from study entry until delivery- anticipated 3 days
Other	Participant Satisfaction	participant satisfaction with labor induction and preference for method of drug administration. This will use a questionnaire developed for this study with some similarity to the referenced Nassar study below.	from study entry until discharge- anticipated 5 days
Primary	Time to Delivery	number of hours from placement of study drug to delivery; Cesarean delivery for fetal non--reassurance indication	from study entry until delivery- anticipated 3 days
Primary	Number of Participants With Cesarean Deliveries Based on Fetal Non-Reassurance Indications	Rate of cesarean deliveries performed for fetal non-reassurance as the indication	from study entry until delivery- anticipated 3 days
Secondary	Number of Vaginal Deliveries That Occurred Within 24 Hours	rate of achieving vaginal delivery within 24 hours	from study entry until delivery- anticipated 3 days
Secondary	Number of Participants Who Had Uterine Hyperstimulation	Presence of uterine hyperstimulation, tachysystole as defined as 6 uterine contractions in a 10 minute period	from study entry until delivery- anticipated 3 days
Secondary	Number of Neonatal Intensive Care Unit (NICU) Admission	Admission to NICU	from study entry until discharge of newborn- anticipated up to 28 days
Secondary	Number of Doses Misoprostol Used	Number of doses of misoprostol needed	from study entry until delivery- anticipated 3 days
Secondary	Uterine Rupture	Presence of uterine rupture	from study entry until delivery- anticipated 3 days
Secondary	Dose of Oxytocin Used for Augmentation	dose of oxytocin used for augmentation of labor	from study entry until delivery- anticipated 3 days
Secondary	Number of Participants With Neonatal Cord Gases Measured	cord gases from newborn	from study entry until delivery- anticipated 3 days