Contact information
Type
Scientific
Primary contact
Dr Graeme Smith
ORCID ID
Contact details
Clinical Research Centre
Queen's University
Kingston General Hospital
76 Stuart Street
Angada 4
Room 5-415
Kingston
K7L 2V7
Canada
+1 613 549 6666 ext. 3936
gns@post.queensu.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
FMI-63194
Study information
Scientific title
A pilot study to evaluate glyceryl trinitrate (GTN) as a novel therapeutic for the prevention and treatment of pre-eclampsia
Acronym
Study hypothesis
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
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)
Study design
Randomised, multicentre, blinded, placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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 names
Glyceryl trinitrate
Primary outcome measures
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
Secondary outcome measures
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
Overall trial start date
01/01/2007
Overall trial end date
31/12/2009
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
80 women in total: prevention arm (40), treatment arm (40)
Participant 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
Recruitment start date
01/01/2007
Recruitment end date
31/12/2009
Locations
Countries of recruitment
Canada
Trial participating centre
Clinical Research Centre
Kingston
K7L 2V7
Canada
Sponsor information
Organisation
Queen's University (Canada)
Sponsor details
99 University Avenue
Kingston
K7L 3N6
Canada
gns@post.queensu.ca
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: FMI-63194)
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