Use of a nitric oxide (ISMN) for the PREVENTION and MANAGEMENT of pre-eclampsia (pilot study)

ISRCTN	ISRCTN45790835
DOI	https://doi.org/10.1186/ISRCTN45790835
Protocol serial number	FMI-63194
Sponsor	Queen's University (Canada)
Funder	Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: FMI-63194)

Submission date: 29/11/2006
Registration date: 21/12/2007
Last edited: 03/03/2009

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Graeme Smith
Scientific

Clinical Research Centre
Queen's University
Kingston General Hospital
76 Stuart Street, Angada 4, Room 5-415
Kingston
K7L 2V7
Canada

Phone	+1 613 549 6666 ext. 3936
Email	gns@post.queensu.ca

Study information

Primary study design	Interventional
Study design	Randomised, multicentre, blinded, placebo-controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A pilot study to evaluate glyceryl trinitrate (GTN) as a novel therapeutic for the prevention and treatment of pre-eclampsia
Study objectives	CIHR Grant Submission Title: Pre-eclampsia: Fetal and Maternal Outcomes and Innovative Therapies To determine if exogenous glyceryl trinitrate (GTN), compared to placebo, will be effective at preventing the development and/or progression of clinical pre-eclampsia.
Ethics approval(s)	Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board, Kingston, Ontario (Canada) approved on the 20th September 2002 (ref: ANAT-017-02)
Health condition(s) or problem(s) studied	Pre-eclampsia
Intervention	The study is a randomised blinded drug/placebo trial. The randomisation scheme was prepared by an independent statistician prior to initiation of the pilot study, and prepared in blocks for if and when Ottawa Hospital comes on board. The study investigators, associated staff, outcome assessor, data analyst and the study participants will all be blinded to the treatment allocation. ISMN and placebo capsules will be prepared to have identical shape, size, color, smell and feel. No form of identification labeling will be visible on either intervention. When a suitable participant is identified, the research nurse coordinator will explain the details and potential risks and benefits of the study. If consent is granted, the research nurse coordinator will determine the treatment assignment for that subject by calling the research pharmacist who will provide the next code indicating the treatment for a given patient. Patients will then be provided with an appropriately labeled package of pills prepared by the hospital pharmacy. Prevention Arm: Experimental intervention: Daily dose of low dose Isosorbide-5-mononitrate (ISMN) (30 mg) beginning after 20 weeks gestation till delivery. Control intervention: Matching placebo containing lactose. Patients randomly assigned to either receive low dose ISMN (30 mg) as stated above or placebo. Management Arm: Experimental intervention: Daily dose of low dose Isosorbide-5-mononitrate (ISMN) (30 mg) following diagnosis of pre-eclampsia after 24 weeks gestation till delivery. Control intervention: Matching placebo containing lactose. Patients randomly assigned to either receive low dose ISMN (30 mg) as stated above or placebo. In both arms of the study, patients will receive standard clinical care. Total duration of treatment in each arm is flexible and based on each individual participant. There is no follow-up after delivery.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Glyceryl trinitrate
Primary outcome measure(s)	Prevention arm: incidence of pre-eclampsia in the ISMN/placebo groups, measured at delivery Treatment arm: randomisation-to-delivery interval between ISMN/placebo groups, measured at delivery
Key secondary outcome measure(s)	1. Serial change in biochemical markers in treatment/no treatment groups in each of the studies, measured at routine obstetrical visits until delivery (generally every 2 weeks) 2. Incidence of any side effects (major or minor), measured at routine obstetrical visits until delivery (generally every 2 weeks) 3. Neonatal outcomes (composite of neonatal morbidity), measured at delivery
Completion date	31/12/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target sample size at registration	80
Key inclusion criteria	Women of childbearing years (approximately 18 - 42 years). Prevention arm: All women with a past obstetrical history of one or more cases of severe early onset pre-eclampsia or later onset severe pre-eclampsia associated with haemolysis, elevated liver enzymes, low blood levels of platelets (HELLP) syndrome. Treatment arm: All women that have been diagnosed with pre-eclampsia that are being followed clinically and that provide informed consent. For a diagnosis of pre-eclampsia a patient must meet all three criteria: 1. Systolic blood pressure greater than 140 mmHg or an increase of 30 mmHg from the participants baseline (with that increase present at two measurements taken 6 hours apart) 2. Diastolic blood pressure greater than 90 mmHg or an increase of 15 mmHg from the participants baseline (with that increase present at two measurements taken 6 hours apart) 3. Proteinuria greater than 0.3 g in 24 hour urine or 2+ on dipstick
Key exclusion criteria	Potential women excluded are those: 1. That have a contraindication to use of isosorbide mononitrate (ISMN) 2. That have either a maternal or foetal indication for delivery 3. That have a diagnosis of severe pre-eclampsia (diastolic blood pressure greater than 100 mmHg; proteinuria greater than 1 g/d), eclampsia, or HELLP syndrome at time of recruitment
Date of first enrolment	01/01/2007
Date of final enrolment	31/12/2009

Locations

Countries of recruitment

Canada

Study participating centre

Clinical Research Centre

Kingston
K7L 2V7
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes