Clinical trial NCT03171480: Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
Official title: Randomized Controlled Trial of Nitric-oxide Donor (NOD) Isosorbide Mononitrate (IMN) Versus Placebo for Induction of Labor in Pregnancies Complicated by Preeclampsia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Preeclampsia
Labor, Premature
Keywords: Preeclampsia
Induction
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2017-05-31
Enrollment: 176
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cesarean Delivery Rate
timeFrame: 7 days
Secondary outcomes:
measure: Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid
timeFrame: during the induction of labor till delivery for all outcomes
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State Medical Center Labor and Delivery Unit
state: Ohio
Study officials:
affiliation: The Ohio State Wexner Medical Center
name: Kara Rood, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1093/oxfordjournals.humrep.a019481.
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(12):CD006901. doi: 10.1002/14651858.CD006901.pub3.
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. doi: 10.1016/s0020-7292(02)00128-5.
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.
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. doi: 10.1111/j.1471-0528.1997.tb12066.x.
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.
citation: Gee SE, Ma'ayeh M, Cackovic H, Samuels P, Thung SF, Landon MB, Rood KM. Addition of vaginal isosorbide mononitrate for labor induction in pregnancies complicated by hypertensive diseases of pregnancy: a randomized controlled trial. Am J Obstet Gynecol MFM. 2021 Jul;3(4):100343. doi: 10.1016/j.ajogmf.2021.100343. Epub 2021 Feb 27.