Labor, Premature, Preeclampsia
Conditions
Keywords
Preeclampsia, Induction
Brief summary
A randomized controlled trial (RCT) of nitric-oxide donor (NOD) isosorbide mononitrate (IMN) versus placebo as an adjuvant to misoprostol/ intra-cervical Foley bulb for induction of labor to decrease rate of cesarean deliveries in pregnancies complicated by preeclampsia (≥24/0 weeks' gestation)
Detailed description
The investigators are proposing a double blinded, placebo controlled, randomized clinical trial of patients undergoing induction of labor for preeclampsia. Once the decision to induce will be taken, the participants will be randomized to receive either intravaginal IMN (40mg) or identical appearing placebo placed every 4hrs in the posterior vaginal fornix X 3 doses. IMN or placebo will be discontinued when active labor occurs or when the physician decides to proceed with augmentation with oxytocin or AROM. Participants will be induced using the investigators routine induction agents, Misoprostol (25 mcg every 4 hrs for maximum of 6 doses) and an intra-cervical foley bulb will be inserted with 2nd dose of IMN or placebo. Regarding management of labor, physician decides when to proceed with augmentation with oxytocin or AROM.
Interventions
DRUGMonoket Pill
Intra-vaginal application of Monoket as a cervical ripening agent for pregnant women undergoing induction of labor
DRUGPlacebo
The pharmacy has compounded an identical appearing placebo
Sponsors
Ohio State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
A double blinded, placebo controlled, randomized clinical trial of patients undergoing induction of labor for preeclampsia. Study drug or identical appearing placebo will be delivered to labor floor by pharmacist, after randomization.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
No
Inclusion criteria
* Women older than 18 years at the time of induction of labor with the ability to give informed consent * Induction of labor for clinical diagnosis of preeclampsia * Unfavorable cervix (Bishop's score of less than 6) * Cervical dilation 2cm or less * Singleton * Gestational age ≥ 24 weeks * English speaking
Exclusion criteria
* • Contraindication to vaginal delivery * Contraindication to misoprostol * Fetal Demise * Major fetal anomaly * Non-english speaking women * HIV * Medical conditions requiring assisted second stage * Category III tracing * Eclampsia * Hemolysis Elevated Liver enzymes Low Platelets syndrome * DIC or active hemorrhage before randomization * Hypersensitivity to isosorbide mononitrate * Isosorbide mononitrate should not be used in cases of acute myocardial infarction with low filling pressure, acute circulatory failure (shock, vascular collapse), or hypertrophic obstructive cardiomyopathy (HOCM), constrictive pericarditis, low cardiac filling pressures, aortic/mitral valve stenosis and diseases associated with a raised intra-cranial pressure e.g following a head trauma and including cerebral hemorrhage. * Isosorbide mononitrate should not be used in patients with severe anemia, severe hypotension, closed angle glaucoma or severe hypovolaemia. * Isosorbide mononitrate tablets contain lactose and therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cesarean Delivery Rate | 7 days | Rate of cesarean section for those enrolled in study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | during the induction of labor till delivery for all outcomes | placenta abruption at time of delivery, administration of IV antihypertensive medication for BP \>160/110, maternal hypotensive defined as \<90/50, Uterine hyperstimulation defined as \>3 contractions in 10 minutes and meconium stained amniotic fluid anytime during labor induction/augmentation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Monoket Pill Isosorbide mononitrate is a drug used principally in the treatment of angina pectoris\[1\] and acts by dilating the blood vessels so as to reduce the blood pressure. It is sold in the USA by Kremers Urban under the trade name Monoket, also sold in the USA under the name Imdur,
Monoket Pill: Intra-vaginal application of Monoket as a cervical ripening agent for pregnant women undergoing induction of labor | 89 |
| Placebo Pill The pharmacy has compounded an identical appearing placebo
Monoket Pill: Intra-vaginal application of Monoket as a cervical ripening agent for pregnant women undergoing induction of labor | 87 |
| Total | 176 |
Baseline characteristics
| Characteristic | Monoket Pill | Placebo Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 89 Participants | 87 Participants | 176 Participants |
| Age, Continuous | 28 years | 27 years | 28 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 89 Participants | 87 Participants | 176 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 89 | 0 / 87 |
| other Total, other adverse events | 0 / 89 | 0 / 87 |
| serious Total, serious adverse events | 0 / 89 | 0 / 87 |
Outcome results
Primary
Cesarean Delivery Rate
Rate of cesarean section for those enrolled in study
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Monoket Pill | Cesarean Delivery Rate | 29 Participants |
| Placebo | Cesarean Delivery Rate | 22 Participants |
Secondary
Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid
placenta abruption at time of delivery, administration of IV antihypertensive medication for BP \>160/110, maternal hypotensive defined as \<90/50, Uterine hyperstimulation defined as \>3 contractions in 10 minutes and meconium stained amniotic fluid anytime during labor induction/augmentation
Time frame: during the induction of labor till delivery for all outcomes
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Monoket Pill | Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | Anti-hypertensives | 29 Participants |
| Monoket Pill | Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | uterine hyperstimulation | 3 Participants |
| Monoket Pill | Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | hypotension | 9 Participants |
| Monoket Pill | Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | MSAF | 0 Participants |
| Monoket Pill | Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | Abruption | 0 Participants |
| Placebo | Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | MSAF | 0 Participants |
| Placebo | Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | Abruption | 0 Participants |
| Placebo | Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | Anti-hypertensives | 32 Participants |
| Placebo | Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | hypotension | 8 Participants |
| Placebo | Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid | uterine hyperstimulation | 1 Participants |