PreeclampsiaPhase 4NOPENCT03171480
Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
A Phase 4 study testing Monoket Pill in people with Preeclampsia and Labor, Premature, run by Ohio State University at 1 site in United States.
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) Read more about this study
- Who is it for?
- Ages 18 to 42 years, women only
- Conditions the study is for
- Preeclampsia, Labor, Premature
- What is being tested?
- Monoket Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 176 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Oct 2017to 1 Jul 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 42 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- • Contraindication to vaginal delivery
- Contraindication to misoprostol
- Fetal Demise
- Major fetal anomaly
- Non-english speaking women
- HIV
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Ohio State Medical Center Labor and Delivery Unit
Columbus, Ohio, 43210
About this study
Official title: Randomized Controlled Trial of Nitric-oxide Donor (NOD) Isosorbide Mononitrate (IMN) Versus Placebo for Induction of Labor in Pregnancies Complicated by Preeclampsia
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)
Read the 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.
- Conditions
- Preeclampsia, Labor, Premature
- Being tested
- Monoket Pill, Placebo
- Keywords
- Preeclampsia, Induction
- Medical subject headings
- Pre-Eclampsia, Obstetric Labor, Premature
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Monoket PillDrug
Also called Isosorbide mononitrate
Intra-vaginal application of Monoket as a cervical ripening agent for pregnant women undergoing induction of labor
PlaceboDrug
The pharmacy has compounded an identical appearing placebo
| Study group | Role | What they receive |
|---|---|---|
| Monoket pill | Experimental | 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, Receives: Drug: Monoket Pill |
| Placebo pill | Placebo comparator | The pharmacy has compounded an identical appearing placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cesarean Delivery Rate
Rate of cesarean section for those enrolled in study
Measured: 7 days
Secondary outcomes (1)
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
Measured: during the induction of labor till delivery for all outcomes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2017
- Study start30 Oct 2017
- Primary completion1 Jul 2020
- Study completion1 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for PreeclampsiaStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kara M Rood, MD, Ohio State University
- Investigators
- Kara Rood, MD, Principal investigator, The Ohio State Wexner Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03171480
- Sponsor's protocol ID
- 2017H0195
- Acronym
- NOPE
- Status last verified
- Dec 2021
- First submitted
- 10 May 2017
- Last updated
- 4 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 8921128Ghosh 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.
PubMed 27918616Chanrachakul 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.
PubMed 12175715El-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.
PubMed 25694257Thomson 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.
PubMed 9307534Collingham 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.
PubMed 20567177Gee 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.
PubMed 33652160
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Nitric-oxide Donor (NOD) Isosorbide Mononitrate (IMN) Versus Placebo for Induction of Labor in Pregnancies Complicated by Preeclampsia
- ClinicalTrials.gov ID
- NCT03171480
- Acronym / sponsor ID
- NOPE / 2017H0195
- Conditions
- Preeclampsia, Labor, Premature
- Keywords
- Preeclampsia, Induction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 176 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Study start
- 30 Oct 2017 (actual)
- Primary completion
- 1 Jul 2020 (actual)
- Study completion
- 1 Jul 2020 (actual)
- First posted
- 31 May 2017 (actual)
- Results
- Posted 4 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Monoket pill | Experimental | Drug: Monoket PillIsosorbide 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, |
| Placebo pill | Placebo comparator | Drug: PlaceboThe pharmacy has compounded an identical appearing placebo |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (15 listed)
- • Contraindication to vaginal delivery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Monoket PillAlso: Isosorbide mononitrateIntra-vaginal application of Monoket as a cervical ripening agent for pregnant women undergoing induction of labor | Drug | Monoket pill |
| PlaceboThe pharmacy has compounded an identical appearing placebo | Drug | Placebo pill |
Primary outcome
Cesarean Delivery Rate
Time frame: 7 days
Rate of cesarean section for those enrolled in study
1 secondary outcome
Placental Abruption, Use of IV Antihypertensive Drug, Maternal Hypotension, Uterine Hyperstimulation and Meconium Stained Fluid
Time frame: during the induction of labor till delivery for all outcomes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8921128Buhimschi 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.
- Background: PubMed 27918616Ghosh 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.
- Background: PubMed 12175715Chanrachakul 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.
- Background: PubMed 25694257El-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.
- Background: PubMed 9307534Thomson 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 publication: PubMed 20567177Collingham 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.
- Derived from this study: PubMed 33652160Gee 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kara Rood, MD principal investigator
The Ohio State Wexner Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Monoket Pill in people with Preeclampsia and Labor, Premature, run by Ohio State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cesarean Delivery Rate (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03171480, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2022.