Condition category
Pregnancy and Childbirth
Date applied
18/12/2002
Date assigned
18/12/2002
Last edited
10/09/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Jane Norman

ORCID ID

Contact details

Department of Obstetrics & Gynaecology
Level 3 - QEB
Glasgow Royal Infirmary
10 Alexandra Parade
Glasgow
G31 2ER
United Kingdom
+44 (0)141 211 4708
goua21@udcf.gla.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

01/02A

Study information

Scientific title

Acronym

Study hypothesis

Double blind trial comparing isosorbide mononitrate with prostaglandin E2 for pre-induction cervical ripening in nulliparous women. Women were randomised to receive vaginally either IMN tablets (40mg) or PGE2 gel (2mg), up to two doses 16 hrs apart. The aims of the study were to test the following hypotheses:
1. IMN (40mg) is as effective as PGE2 gel (dinoprostone 2 mg) for cervical ripening prior to the induction of labour at term.
2. IMN (40mg) is associated with a lower incidence of uterine
hyperstimulation than PGE2 gel (dinoprostone 2mg) for cervical ripening prior to the induction of labour at term.
3. IMN (40mg) is associated with a zero incidence of abnormal fetal heart rate (FHR) patterns, vaginal bleeding, uterine hypertonus and hypotension requiring treatment, and thus would be safe to use in an outpatient setting.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Obstetrics and gynaecology

Intervention

Randomised to one of two treatment groups on up to two occasions:
1. Isosorbide mononitrate tablet 40 mg administered vaginally (n = 200)
2. Prostaglandin gel (dinoprostone) 800 ug administered vaginally (n = 200).

Each treatment given on up to two occasions: after recruitment and 16 h later. If Bishop score found to be more than 6, cervical ripening agent will be withheld and fetal membranes ruptured to induce labour.

Women who go into labour during the ripening process will be managed according to an 'active management of labour' protocol, and further ripening agents withheld.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

The study examined primary outcomes of safety and efficacy. The cervical ripening effect of each agent was assessed as change in modified Bishop
score at each treatment insertion (16 hours and 24 hours) over pre-randomisation modified Bishop score. Frequency and duration of uterine
contractions was assessed at 2, 4, 6, 16, 18, 20, 22 and 24 hours, in order to calculate the incidence of uterine hyperstimulation (defined as uterine tachysystole [more than 5 uterine contractions per 10 minutes for at least
20 minutes] with or without FHR changes). 14 We also recorded the frequency of events during ripening that would be hazardous for mother or baby if cervical ripening had been performed on an outpatient basis (any of: abnormal FHR patterns, maternal hypotension requiring treatment, uterine hypertonus or vaginal bleeding). Abnormal FHR patterns were assessed by cardiotocography performed from 30 minutes prior to drug administration until one hour after, and then at 6, 15.5, 17 and 24 hours or continuously once uterine contractions ensued. Cardiotocograph tracings were rated normal, suspicious or pathological according to the Royal College of Obstetricians and Gynaecologists guidelines on the use of electronic fetal
monitoring.13 On conclusion of the trial, the abnormal FHR patterns were reviewed by an independent Obstetrician whilst blind to treatment
allocation. Hypotension requiring treatment was assessed by maternal pulse and blood pressure measurements at 1, 2, 6, 16, 17 and 24 hours using an automated device (DinamapĀ®, Critikon Company, Tampa, Fla). Vaginal bleeding
during the cervical ripening period (first drug treatment to 24 hours) was prospectively ascertained by examination or patient enquiry.
All primary outcomes were ascertained during the first 24 hour study period, during treatment solely with either IMN or PGE2, and prior to rescue
treatment with PGE2 where applied.

Secondary outcome measures

1. The incidence of maternal
side effects over the preceding 6 hours (assessed by a structured
questionnaire at 6, 16 and 22 hours)
2. The timings and maternal outcomes of the subsequent labour
3. Fetal outcomes
4. Maternal satisfaction
with cervical ripening treatment (measured by a visual analogue score [VAS]
prior to discharge from hospital), 5. Preference for inpatient or outpatient cervical ripening
6. Any events requiring hospital admission or referral.

Overall trial start date

01/10/2001

Overall trial end date

30/11/2003

Reason abandoned

Eligibility

Participant inclusion criteria

Consenting pregnant women admitted to Glasgow Royal Maternity Hospital for cervical ripening prior to the induction of labour at term who fulfil the criteria:
1. Singleton fetus
2. Cephalic presentation greater than or equal to 38 completed weeks gestation
3. Modified cervical (Bishop) score of less than or equal to 6

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

400

Participant exclusion criteria

1. Patients with any of the contraindications listed in the British National Formulary to PGE2 (active cardiac, pulmonary, renal or
hepatic disease, placenta praevia or unexplained vaginal bleeding during pregnancy and ruptured membranes, major cephalopelvic disproportion or fetalmalpresentation, history of Caesarean section or major uterine surgery, untreated pelvic infection and fetal distress) or IMN (hypersensitivity to nitrates, hypotensive conditions and hypovolaemia, hypertrophic obstructive cardiomyopathy, aortic or mitral stenosis, cardiac tamponade, constrictive pericarditis, marked anaemia and closed-angle glaucoma).
2. Other exclusion criteria were delivery mandatory within the next 48 hours in the maternal or fetal interest, one or more births >23 weeks gestation, age <16 years, or ruptured fetal membranes.

Recruitment start date

01/10/2001

Recruitment end date

30/11/2003

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Obstetrics & Gynaecology
Glasgow
G31 2ER
United Kingdom

Sponsor information

Organisation

The Sir Jules Thorn Charitable Trust (UK)

Sponsor details

24 Manchester Square
London
W1U 3TH
United Kingdom
+44 (0)20 7487 5851
julesthorntrust@compuserve.com

Sponsor type

Charity

Website

http://www.julesthorntrust.org.uk/

Funders

Funder type

Charity

Funder name

The Sir Jules Thorn Charitable Trust (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2006 results in http://www.ncbi.nlm.nih.gov/pubmed/16580290

Publication citations

  1. Results

    Osman I, MacKenzie F, Norrie J, Murray HM, Greer IA, Norman JE, The "PRIM" study: a randomized comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening before the induction of labor at term., Am. J. Obstet. Gynecol., 2006, 194, 4, 1012-1021, doi: 10.1016/j.ajog.2005.10.812.

Additional files

Editorial Notes