Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Controlled Trial of Nitric-oxide Donor (NOD) Isosorbide Mononitrate (IMN) Versus Placebo for Induction of Labor in Pregnancies Complicated by Preeclampsia

Conditions
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Preeclampsia, Labor, Premature

Intervention / Treatment
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* Drug: Monoket Pill
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monoket pill<br>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, | Drug: Monoket Pill<br>* Intra-vaginal application of Monoket as a cervical ripening agent for pregnant women undergoing induction of labor<br>* Other names: Isosorbide mononitrate;|
| Placebo Comparator: Placebo pill<br>The pharmacy has compounded an identical appearing placebo | Drug: Placebo<br>* The pharmacy has compounded an identical appearing placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cesarean Delivery Rate | Rate of cesarean section for those enrolled in study | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | during the induction of labor till delivery for all outcomes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preeclampsia, Induction