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
Secondary identifying numbers 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

Study designRandomised, multicentre, blinded, placebo-controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleA pilot study to evaluate glyceryl trinitrate (GTN) as a novel therapeutic for the prevention and treatment of pre-eclampsia
Study objectivesCIHR 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) studiedPre-eclampsia
InterventionThe 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Glyceryl trinitrate
Primary outcome measurePrevention 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 measures1. 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 study start date01/01/2007
Completion date31/12/2009

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexFemale
Target number of participants80 women in total: prevention arm (40), treatment arm (40)
Key inclusion criteriaWomen 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 participant’s 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 participant’s 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 criteriaPotential 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 enrolment01/01/2007
Date of final enrolment31/12/2009

Locations

Countries of recruitment

  • Canada

Study participating centre

Clinical Research Centre
Kingston
K7L 2V7
Canada

Sponsor information

Queen's University (Canada)
University/education

99 University Avenue
Kingston
K7L 3N6
Canada

Email gns@post.queensu.ca
Website http://www.queensu.ca/homepage/
ROR logo "ROR" https://ror.org/02y72wh86

Funders

Funder type

Research organisation

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: FMI-63194)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan