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

NCT ID: NCT02408315

Last Updated: 2022-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2021-12-31

Brief 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.

Detailed 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.

Conditions

Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: TRIPLE

Study Groups

misoprostol/placebo using buccal

Randomized for buccal route of administration/ placebo

Group Type: PLACEBO_COMPARATOR

misoprostol/placebo

Intervention Type: DRUG

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

misoprostol/placebo using vaginal

Randomized for vaginal route of administration/ placebo

Group Type: PLACEBO_COMPARATOR

misoprostol/placebo

Intervention Type: DRUG

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

Interventions

misoprostol/placebo

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

Intervention Type: DRUG

Other Intervention Names

Cytotec

Eligibility Criteria

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

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

David Haas

Professor Vice Chair for Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David M Haas, MD

Role: PRINCIPAL_INVESTIGATOR

IU School of Medicine

Locations

IU Health Methodist Hospital

Indianapolis, Indiana, United States

Sidney and Lois Eskenazi Hospital

Indianapolis, Indiana, United States

Countries

United States

References

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. doi: 10.1111/j.1471-0528.2007.01492.x.

Reference Type: BACKGROUND

PMID: 17877674 (View on PubMed)

Vorontsova Y, Haas DM, Flannery K, Masters AR, Silva LL, Pierson RC, Yeley B, Hogg G, Guise D, Heathman M, Quinney SK. Pharmacokinetics of vaginal versus buccal misoprostol for labor induction at term. Clin Transl Sci. 2022 Aug;15(8):1937-1945. doi: 10.1111/cts.13306. Epub 2022 Jun 12.

Reference Type: DERIVED

PMID: 35587540 (View on PubMed)

Haas DM, Daggy J, Flannery KM, Dorr ML, Bonsack C, Bhamidipalli SS, Pierson RC, Lathrop A, Towns R, Ngo N, Head A, Morgan S, Quinney SK. A comparison of vaginal versus buccal misoprostol for cervical ripening in women for labor induction at term (the IMPROVE trial): a triple-masked randomized controlled trial. Am J Obstet Gynecol. 2019 Sep;221(3):259.e1-259.e16. doi: 10.1016/j.ajog.2019.04.037. Epub 2019 May 7.

Reference Type: DERIVED

PMID: 31075246 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IMPROVE

Identifier Type: -

Identifier Source: org_study_id