PregnancyPhase 3IMPROVENCT02408315
Induction With Misoprostol: Oral Mucosa Versus Vaginal Epithelium (IMPROVE)
A Phase 3 study of Pregnancy, run by Indiana University at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 14 to 45 years, women only
- Conditions the study is for
- Pregnancy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2015to Dec 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 45 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
IU Health Methodist Hospital
Indianapolis, Indiana, 46202
Sidney and Lois Eskenazi Hospital
Indianapolis, Indiana, 46202
About this study
Official title: Induction With Misoprostol: Oral Mucosa Versus Vaginal Epithelium
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.
Read the 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:
- 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.
- 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.
- 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
- Being tested
- misoprostol/placebo
- Keywords
- induction of labor, safety, pharmacokinetic, misoprostol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
misoprostol/placeboDrug
Also called Cytotec
buccal or vaginal routes of administration/ placebo to compare methods for efficacy and safety during induction.
| Study group | Role | What they receive |
|---|---|---|
| misoprostol/placebo using buccal | Placebo comparator | Randomized for buccal route of administration/ placebo Receives: Drug: misoprostol/placebo |
| misoprostol/placebo using vaginal | Placebo comparator | Randomized for vaginal route of administration/ placebo Receives: Drug: misoprostol/placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Delivery
number of hours from placement of study drug to delivery
Cesarean delivery for fetal non--reassurance indication
Measured: from study entry until delivery- anticipated 3 days
Number of Participants With Cesarean Deliveries Based on Fetal Non-Reassurance Indications
Rate of cesarean deliveries performed for fetal non-reassurance as the indication
Measured: from study entry until delivery- anticipated 3 days
Secondary outcomes (7)
Number of Vaginal Deliveries That Occurred Within 24 Hours
rate of achieving vaginal delivery within 24 hours
Measured: from study entry until delivery- anticipated 3 days
Number of Participants Who Had Uterine Hyperstimulation
Presence of uterine hyperstimulation, tachysystole as defined as 6 uterine contractions in a 10 minute period
Measured: from study entry until delivery- anticipated 3 days
Number of Neonatal Intensive Care Unit (NICU) Admission
Admission to NICU
Measured: from study entry until discharge of newborn- anticipated up to 28 days
Number of Doses Misoprostol Used
Number of doses of misoprostol needed
Measured: from study entry until delivery- anticipated 3 days
Uterine Rupture
Presence of uterine rupture
Measured: from study entry until delivery- anticipated 3 days
Dose of Oxytocin Used for Augmentation
dose of oxytocin used for augmentation of labor
Measured: from study entry until delivery- anticipated 3 days
Number of Participants With Neonatal Cord Gases Measured
cord gases from newborn
Measured: from study entry until delivery- anticipated 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2015 (estimated)
- Study startSep 2015
- Primary completionNov 2017
- Study completionDec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PregnancyStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Haas, Indiana University
- Investigators
- David M Haas, MD, Principal investigator, IU School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02408315
- Sponsor's protocol ID
- IMPROVE
- Acronym
- IMPROVE
- Status last verified
- Mar 2022
- First submitted
- 10 Feb 2015
- Last updated
- 13 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Will share as needed for IPD.
Publications
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.
PubMed 17877674Vorontsova 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.
PubMed 35587540Haas 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.
PubMed 31075246
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction With Misoprostol: Oral Mucosa Versus Vaginal Epithelium
- ClinicalTrials.gov ID
- NCT02408315
- Acronym / sponsor ID
- IMPROVE / IMPROVE
- Conditions
- Pregnancy
- Keywords
- induction of labor, safety, pharmacokinetic, misoprostol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Nov 2017 (actual)
- Study completion
- Dec 2021 (actual)
- First posted
- 3 Apr 2015 (estimated)
- Results
- Posted 9 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
- 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| misoprostol/placebo using buccal | Placebo comparator | Drug: misoprostol/placeboRandomized for buccal route of administration/ placebo |
| misoprostol/placebo using vaginal | Placebo comparator | Drug: misoprostol/placeboRandomized for vaginal route of administration/ placebo |
Who may qualify
- Ages
- 14 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| misoprostol/placeboAlso: Cytotecbuccal or vaginal routes of administration/ placebo to compare methods for efficacy and safety during induction. | Drug | misoprostol/placebo using buccal, misoprostol/placebo using vaginal |
Primary outcome
Time to Delivery
Time frame: from study entry until delivery- anticipated 3 days
number of hours from placement of study drug to delivery Cesarean delivery for fetal non--reassurance indication
Number of Participants With Cesarean Deliveries Based on Fetal Non-Reassurance Indications
Time frame: from study entry until delivery- anticipated 3 days
Rate of cesarean deliveries performed for fetal non-reassurance as the indication
7 secondary outcomes
Number of Vaginal Deliveries That Occurred Within 24 Hours
Time frame: from study entry until delivery- anticipated 3 days
Number of Participants Who Had Uterine Hyperstimulation
Time frame: from study entry until delivery- anticipated 3 days
Number of Neonatal Intensive Care Unit (NICU) Admission
Time frame: from study entry until discharge of newborn- anticipated up to 28 days
Number of Doses Misoprostol Used
Time frame: from study entry until delivery- anticipated 3 days
Uterine Rupture
Time frame: from study entry until delivery- anticipated 3 days
Dose of Oxytocin Used for Augmentation
Time frame: from study entry until delivery- anticipated 3 days
Number of Participants With Neonatal Cord Gases Measured
Time frame: from study entry until delivery- anticipated 3 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17877674Nassar 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.
- Derived from this study: PubMed 35587540Vorontsova 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.
- Derived from this study: PubMed 31075246Haas 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.
- Individual participant dataSharing planned: Yes. Will share as needed for IPD.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David M Haas, MD principal investigator
IU School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study of Pregnancy, run by Indiana University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Delivery (time frame: from study entry until delivery- anticipated 3 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02408315, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2022.