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

Primary Purpose

Preeclampsia, Labor, Premature

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Monoket Pill
Placebo
Sponsored by
Ohio State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Preeclampsia focused on measuring Preeclampsia, Induction

Eligibility Criteria

18 Years - 42 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • The Ohio State Medical Center Labor and Delivery Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Monoket pill

Placebo pill

Arm Description

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,

The pharmacy has compounded an identical appearing placebo

Outcomes

Primary Outcome Measures

Cesarean Delivery Rate
Rate of cesarean section for those enrolled in study

Secondary Outcome Measures

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

Full Information

First Posted
May 10, 2017
Last Updated
December 7, 2021
Sponsor
Ohio State University
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1. Study Identification

Unique Protocol Identification Number
NCT03171480
Brief Title
Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
October 30, 2017 (Actual)
Primary Completion Date
July 1, 2020 (Actual)
Study Completion Date
July 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preeclampsia, Labor, Premature
Keywords
Preeclampsia, Induction

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
176 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Monoket pill
Arm Type
Experimental
Arm Description
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,
Arm Title
Placebo pill
Arm Type
Placebo Comparator
Arm Description
The pharmacy has compounded an identical appearing placebo
Intervention Type
Drug
Intervention Name(s)
Monoket Pill
Other Intervention Name(s)
Isosorbide mononitrate
Intervention Description
Intra-vaginal application of Monoket as a cervical ripening agent for pregnant women undergoing induction of labor
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
The pharmacy has compounded an identical appearing placebo
Primary Outcome Measure Information:
Title
Cesarean Delivery Rate
Description
Rate of cesarean section for those enrolled in study
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid
Description
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

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
only pregnant women with preeclampsia
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
42 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kara Rood, MD
Organizational Affiliation
The Ohio State Wexner Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ohio State Medical Center Labor and Delivery Unit
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
8921128
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.
Results Reference
background
PubMed Identifier
27918616
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.
Results Reference
background
PubMed Identifier
12175715
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.
Results Reference
background
PubMed Identifier
25694257
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.
Results Reference
background
PubMed Identifier
9307534
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.
Results Reference
background
PubMed Identifier
20567177
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.
Results Reference
result
PubMed Identifier
33652160
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.
Results Reference
derived

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

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