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

Preeclampsia Clinical Trial

— NOPE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03171480
• Other study ID #: 2017H0195
• Status: Completed
• Phase: Phase 4
• Start date: October 30, 2017
• Est. completion date: July 1, 2020

Study information

• Verified date: December 2021
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: July 1, 2020
• Est. primary completion date: July 1, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

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.

Related Conditions & MeSH terms

• Labor, Premature
• Obstetric Labor, Premature
• Pre-Eclampsia
• Preeclampsia

Intervention

Drug:
• Monoket Pill
Intra-vaginal application of Monoket as a cervical ripening agent for pregnant women undergoing induction of labor
• Placebo
The pharmacy has compounded an identical appearing placebo

Locations

Country	Name	City	State
United States	The Ohio State Medical Center Labor and Delivery Unit	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University

Country where clinical trial is conducted

United States, 

References & Publications (6)

Buhimschi I, Ali M, Jain V, Chwalisz K, Garfield RE. Differential regulation of nitric oxide in the rat uterus and cervix during pregnancy and labour. Hum Reprod. 1996 Aug;11(8):1755-66. — View Citation

Chanrachakul B, Herabutya Y, Punyavachira P. Randomized trial of isosorbide mononitrate versus misoprostol for cervical ripening at term. Int J Gynaecol Obstet. 2002 Aug;78(2):139-45. — View Citation

Collingham JP, Fuh KC, Caughey AB, Pullen KM, Lyell DJ, El-Sayed YY. Oral misoprostol and vaginal isosorbide mononitrate for labor induction: a randomized controlled trial. Obstet Gynecol. 2010 Jul;116(1):121-126. doi: 10.1097/AOG.0b013e3181e408f2. — View Citation

El-Khayat W, Alelaiw H, El-kateb A, Elsemary A. Comparing vaginal misoprostol versus Foley catheter plus vaginal isosorbide mononitrate for labor induction. J Matern Fetal Neonatal Med. 2016;29(3):487-92. doi: 10.3109/14767058.2015.1007036. Epub 2015 Feb 19. — View Citation

Ghosh A, Lattey KR, Kelly AJ. Nitric oxide donors for cervical ripening and induction of labour. Cochrane Database Syst Rev. 2016 Dec 5;12:CD006901. doi: 10.1002/14651858.CD006901.pub3. Review. — View Citation

Thomson AJ, Lunan CB, Cameron AD, Cameron IT, Greer IA, Norman JE. Nitric oxide donors induce ripening of the human uterine cervix: a randomised controlled trial. Br J Obstet Gynaecol. 1997 Sep;104(9):1054-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cesarean Delivery Rate	Rate of cesarean section for those enrolled in study	7 days
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	during the induction of labor till delivery for all outcomes