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 measure
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 (Dinamap®, 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 (if study stopped)
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
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
Basic results (scientific)
Publication list
2006 results in http://www.ncbi.nlm.nih.gov/pubmed/16580290
Publication citations
-
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.