Induction With Misoprostol: Oral Mucosa Versus Vaginal Epithelium (IMPROVE)
| Status: | Recruiting |
|---|---|
| Conditions: | Women's Studies |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 14 - 45 |
| Updated: | 8/3/2016 |
| Start Date: | September 2015 |
| End Date: | December 2017 |
| Contact: | David M Haas, MD |
| Email: | dahaas@iu.edu |
| Phone: | 317-880-3949 |
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.
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.
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.
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.
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
We found this trial at
2
sites
Indianapolis, Indiana 46202
Principal Investigator: David M Haas, MD, MS
Phone: 317-880-3961
Click here to add this to my saved trials
Indianapolis, Indiana 46202
Principal Investigator: David M Haas, MD, MS
Phone: 317-880-3961
Click here to add this to my saved trials