Contact information
Type
Scientific
Primary contact
Prof Harvey White
ORCID ID
Contact details
Director of Coronary Care & Green Lane Cardiovascular Research Unit
Green Lane Cardiovascular Service
Auckland City Hospital
Private Bag 92 024
Auckland
1001
New Zealand
HarveyW@adhb.govt.nz
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Neu-GPE-CPB-001
Study information
Scientific title
Acronym
SNUG-2
Study hypothesis
In 2004, the American College of Cardiology/American Heart Association (ACC/AHA) Task Force described the occurrence of adverse neurological outcomes as either Type 1 or Type 2 injuries. Type 1 injuries are predominantly focal stroke, transient ischaemic attack and fatal cerebral injuries. Type 2 events reflect a more global/diffuse injury with disorientation or immediate or intellectual decline. The Task Force reports that 53% of Cardiopulmonary Bypass (CPB) - Coronary Artery Bypass Graft (CABG) patients experience Type 2 abnormal neurocognitive function at the time of hospital discharge. Six months after surgery, abnormalities could still be identified in 24% of patients.
Hypothesis:
To determine whether Glypromate® may provide neurocognitive preservation and reduction of memory loss.
This new phase 3 trial is a follow-on from the earlier phase 2 study registered under ISRCTN67437862.
Please note that, as of 13/08/2008, the number of participants on this ISRCTN record has been amended from 672 to 350. On 30/06/2008, the target number of participants was reduced to 350, due to high quality of data and fewer drop outs than expected. Recruitment has been completed as the new target number has been achieved. They were recruited from 11 sites in Australia, 6 sites in New Zealand and 7 sites in the USA. The trial is now in follow-up phase.
Ethics approval
The study was approved at 6 New Zealand sites. Lead site, Mercy Ascot Hospital, was approved by the Multi-Region Ethics Committee on 5 July 2007 (ref: MEC/07/02/025).
The study was approved at 11 Australian sites. Lead site, Ashford Hospital, was approved by Bellberry Human Research Ethics Committee on 16 July 2007 (ref: 60/07).
The study was approved at 7 US sites. Lead site, Union Memorial Hospital, was approved by MedStar Research Institute on 18 October 2007 (ref: 2007-238).
Study design
International, randomised, double-blind, placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Cardiopulmonary bypass surgery
Intervention
A four-hour continuous intravenous (i.v.) infusion of Glypromate® 1 mg/kg/hr or placebo will be commenced on completion of protamine administration following cardiopulmonary bypass.
Intervention type
Drug
Phase
Phase III
Drug names
Glypromate®
Primary outcome measures
This study has co-primary endpoints measured by the composite Z score for cognition and the composite score for the ADL assessment. The primary analyses will compare effects of Glypromate® and placebo-based on the standardised composite cognitive change scores and the ADL scores. The total composite cognitive change score is calculated as the corrected directional sum of the changes in the five individual domain components plus three ancillary tests, i.e. the Pegboard Test, Stroop Test and Trail Making Test (adjusted for direction). The test battery comprises 12 tests, 9 from the Cognitive Drug Research's (CDR) computerised cognitive assessment system plus Trail Making Test (parts A & B), Stroop Test (congruent and incongruent), and Lafayette Grooved Regboard Test.
The co-primary instrumental and physical ADL assessments used in this study are from the Older Americans Resources and Services (OARS) Multidimensional Functional Assessment Questionnaire, Centre for the Study of Aging and Human Development, Duke University.
Primary outcome measures are collected at baseline (pre-surgery), 4 - 6 weeks post surgery and 12 - 14 weeks post surgery.
Secondary outcome measures
1. Global evaluation of the patient's ability to perform activities of daily living (question 101 from the OARS Multidimensional Functional Questionnaire)
2. The incidence of stroke and Transient Ischaemic Attack (TIA) after CPB surgery
3. The change in cognitive domain (power of attention, continuity of attention, quality of working memory, quality of episodic memory, speed of memory) and individual cognitive test performance
Secondary outcome measures are assessed at the same timepoints as per the primary measures and in addition an assessment is made on Day 2 post surgery for stroke and TIA.
Overall trial start date
01/06/2007
Overall trial end date
31/12/2008
Reason abandoned
Eligibility
Participant inclusion criteria
1. Scheduled for non-emergency CABG surgery and/or valve replacement/repair, with CPB
2. Willing to provide written informed consent
3. Able and agreeable to undergo all cognitive and Activities of Daily Living (ADL) testing (i.e. understands English, able to read, write, have sufficient motor dexterity and be available for follow-up visit at 4 - 6 weeks and 12 - 14 weeks post surgery)
4. Greater than or equal to 50 years old
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
350
Participant exclusion criteria
1. Pre-operative mechanical assist device or intra-aortic balloon pump inserted for shock or low output syndrome
2. Women of child-bearing potential or breastfeeding women
3. History of or any current condition that in the Investigator's opinion would interfere with study participation or evaluation of results
4. Congenital heart disease with a risk of polycythaemia, circulatory problems, or need for a shunt
5. Renal insufficiency (serum creatinine greater than 180 umol/L [greater than 2 mg/dL])
6. Past or present bleeding disorder
7. History of organic brain syndrome
8. Currently receiving treatment for alcohol or drug abuse
9. Currently participating in another investigational drug or device study
10. Prior enrolment in this study
Recruitment start date
01/06/2007
Recruitment end date
31/12/2008
Locations
Countries of recruitment
Australia, New Zealand, United States of America
Trial participating centre
Director of Coronary Care & Green Lane Cardiovascular Research Unit
Auckland
1001
New Zealand
Sponsor information
Organisation
Neuren Pharmaceuticals Limited (New Zealand)
Sponsor details
c/o Dr Blair Dickman
PO Box 9923
Newmarket
Auckland
1149
New Zealand
bdickman@neurenpharma.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Neuren Pharmaceuticals Limited (New Zealand)
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