Contact information
Type
Scientific
Primary contact
Prof Thompson G Robinson
ORCID ID
Contact details
Department of Cardiovascular Sciences
University of Leicester
Robert Kilpatrick Clinical Sciences Building
Leicester Royal Infirmary
Leicester
LE2 7LX
United Kingdom
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tgr2@leicester.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
2134
Study information
Scientific title
A multicentre, prospective, randomised, open, blinded-endpoint study to assess whether existing antihypertensive therapy should be continued or discontinued within 24-hours of stroke onset and for the subsequent two weeks
Acronym
COSSACS
Study hypothesis
Up to 40% of acute stroke patients on hospital admission are already taking antihypertensive therapy, and most will develop elevated blood pressure levels as an acute complication of the stroke. However, no guidelines exist as to whether antihypertensive therapy should be continued or discontinued following acute stroke. The Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS) is a multicentre, prospective, randomised, open, blinded-endpoint study to assess whether existing antihypertensive therapy should be continued or discontinued within 24-hours of stroke onset and for the subsequent two weeks.
A study population of 2900 patients with both cerebral infarction and haemorrhage on antihypertensive treatment at hospital admission will be recruited giving the study a 90% power at the 5% significance level to detect a relative reduction of 10% (absolute risk reduction of 6%) in death and dependency between continuation and discontinuation groups at two weeks. Non-dysphagic, hospital-admitted stroke patients will be recruited within 24 hours of stroke onset and also within 24 hours of last dose of pre-existing antihypertensive therapy.
Baseline investigations will include: blood pressure measurement using UA-767 monitor, modified Rankin Score, Barthel Index, National Institutes of Health Stroke Score and Oxfordshire Community Stroke Project Classification. Patients will be centrally randomised by telephone to continue or discontinue pre-existing antihypertensive treatment for a two-week period. Blood pressure, modified Rankin Score, Barthel Index and National Institutes of Health Stroke Score will be repeated at 2 weeks by an observer blinded to the randomised group. Mortality and health-related quality of life outcomes will be centrally recorded at 6 months.
Ethics approval
Trent Research Ethics Committee, 22/08/2002, ref: 02/4/051
Study design
Multicentre randomised interventional treatment trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Topic: Stroke Research Network; Subtopic: Acute Care; Disease: Therapy type
Intervention
Baseline investigations include blood pressure measurement using UA-767 monitor, modified Rankin Score, Barthel Index, National Institutes of Health Stroke Score and Oxfordshire Community Stroke Project Classification.
Patients will be centrally randomised by telephone to continue or discontinue pre-existing antihypertensive treatment for a two-week period.
Blood pressure, modified Rankin Score, Barthel Index and National Institutes of Health Stroke Score will be repeated at 2 weeks by an observer blinded to the randomised group. Mortality and health-related quality of life outcomes will be centrally recorded at 6 months.
Follow-up length: 6 months
Study entry: single randomisation only
Intervention type
Other
Phase
Phase III
Drug names
Primary outcome measures
Death or dependancy (modified Rankin Score greater than 3) at 2 weeks post-randomisation
Secondary outcome measures
Early outcomes, measured at 2 weeks and 6 months:
1. Neurological deterioration
2. Functional status
3. Blood pressure changes from admission and discharge
Late outcomes:
4. Death and dependency
5. Fatal and non-fatal stroke recurrence
6. Functional status
7. Health-related quality of life
Overall trial start date
01/01/2001
Overall trial end date
31/03/2009
Reason abandoned
Eligibility
Participant inclusion criteria
1. Aged greater than or equal to 18 years, either sex
2. Stroke onset greater than or equal to 48 hours (for suspected stroke, onset time is last time patient was asymptomatic)
3. Clinical diagnosis of suspected stroke by neuroimaging before or after study entry to exclude non-stroke diagnoses and define stroke type
4. Currently receiving antihypertensive treatment and within 48 hours or last dose
5. Informed patient consent or relative/carer consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned sample size: 3000; UK sample size: 3000
Participant exclusion criteria
1. Hypertensive encephalopathy
2. Hypertension greater than 200/120 mmHg in association with intracerebral haemorrhage
3. Co-existing cardiac or vascular emergency
4. Contraindications to stopping antihypertensive therapy
5. Impaired conscious level
6. Dysphagia
7. Premorbid dependence
8. Co-existing life-threatening condition with life expectancy less than 6 months
9. Females of child-bearing potential
10. Non-stroke diagnoses
Recruitment start date
01/01/2001
Recruitment end date
31/03/2009
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Leicester
Leicester
LE2 7LX
United Kingdom
Sponsor information
Organisation
University Hospitals of Leicester NHS Trust (UK)
Sponsor details
Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Health Foundation (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
Results - basic reporting
Publication summary
2005 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/15662235
2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20621562
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25908462
Publication citations
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Protocol
COSSACS (Continue or Stop post-Stroke Antihypertensives Collaborative Study): rationale and design., J. Hypertens., 2005, 23, 2, 455-458.
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Results
Robinson TG, Potter JF, Ford GA, Bulpitt CJ, Chernova J, Jagger C, James MA, Knight J, Markus HS, Mistri AK, Poulter NR, , Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial., Lancet Neurol, 2010, 9, 8, 767-775, doi: 10.1016/S1474-4422(10)70163-0.
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Results
Manning LS, Mistri AK, Potter J, Rothwell PM, Robinson TG, Short-Term Blood Pressure Variability in Acute Stroke: Post Hoc Analysis of the Controlling Hypertension and Hypotension Immediately Post Stroke and Continue or Stop Post-Stroke Antihypertensives Collaborative Study Trials, Stroke, 2015, doi: 10.1161/STROKEAHA.115.009078.