The purpose of this trial is to assess whether the blood pressure lowering agent candesartan (an angiotensin receptor type 1 blocker) is effective when given to patients with acute stroke and elevated blood pressure.

Hypothesis: AT1 receptor blockade with candesartan in acute stroke will: 1. reduce the risk of death or major disability at 6 months by a 6% absolute risk reduction, relative to placebo. 2. reduce the risk of the combined event of “vascular” death, myocardial infarction, or stroke during the first 6 months by a 25% relative risk reduction, relative to placebo

Condition	Intervention	Phase
Stroke	Drug: Candesartan cilexetil	Phase III

Further Study Details: 

Primary Outcomes: 1. Death or major disability (defined by the modified Rankin scale) at 6 months; 2. The composite event “vascular” death, myocardial infarction, or stroke during the first 6 months
Secondary Outcomes: Clinical outcomes:• Scandinavian Stroke Scale score at 7 days and 6 months; • Modified Rankin scale score at 1, 3, and 6 months; • Barthel Index score at 6 months; • EuroQol score at 6 months; • Mini-Mental State score at 6 months; Adverse events (during the 6 months’ follow-up period):• Death (all-cause death and “vascular” death); • Recurrent stroke (ischaemic, haemorrhagic, or unspecified); • Myocardial infarction; • Combination of the above events; • Adverse events (symptomatic hypotension, renal failure, etc.); Health-economic measures: Costs related to: • Length of hospital stay; • Discharge disposition; • Re-hospitalisations during the first 6 months
Expected Total Enrollment:  2500

It has long been a controversy whether elevated blood pressure should be lowered in the acute phase of stroke. Current clinical practice is generally to accept high blood pressure in the acute phase of stroke, to avoid reduction of cerebral blood perfusion. This practice has a well-founded theoretical basis, but is not supported by evidence from clinical trials. The newly published study ACCESS (Stroke 2003;34:1699) showed a clear beneficial effect of the angiotensin receptor blocker candesartan in the acute phase of stroke, but the trial was seriously underpowered.

The Scandinavian Candesartan Acute Stroke Trial (SCAST) is designed to provide reliable data on the effects of candesartan in a wide variety of patients with acute stroke (target recruitment 2,500). Patients presenting with acute stroke (<30 hours) and systolic blood pressure ≥140 mm Hg will be randomly assigned to candesartan 4 to 16 mg once daily or matching placebo for 7 days, followed by candesartan treatment for 6 months for patients who are hypertensive at the end of the treatment period (at clinician''''s discretion). Follow-up will be performed double-blind at 30 days, 3 months and 6 months.

The trial is co-ordinated from Ullevaal University Hospital in Oslo, Norway. Over 100 centres from Norway, Sweden and Denmark have agreed to participate. Financial contributors: The Eastern Norway Regional Health Authority, AstraZeneca, and Ullevaal University Hospital (Oslo). AstraZeneca will supply drugs and placebo for the trial.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Clinical stroke syndrome with limb paresis, not likely to represent a transient ischaemic attack or non-stroke pathology (e.g. cerebral tumour)
• Systolic blood pressure ≥ 140 mm Hg
• Trial treatment possible within 30 hrs of symptom onset. If time of onset is not known, use the time when the patient was last known to be well.
• Consent (subsidiary, assent from legal acceptable representative, or waiver of consent)
• Age >18 years

Exclusion Criteria:

• Markedly reduced consciousness (i.e. Scandinavian Stroke Scale consciousness score ≤ 2)
• Patient already receiving AT1 receptor blocker
• Contraindication to treatment with AT1 receptor blocker, e.g.: • known renal failure (women: creatinine ≥ 150 µmol/L; men: ≥ 180 µmol/L) • previously diagnosed bilateral renal artery stenosis • previously diagnosed high-grade aortic stenosis • previously diagnosed seriously impaired liver function and/or cholestasis • known intolerance to candesartan or other tablet ingredients
• Clear indication, in the clinician’s view, for start of treatment with AT1 receptor blocker during the treatment period (e.g. chronic heart failure grade III-IV, in the presence of intolerance to ACE inhibitors)
• Clear indication, in the clinician’s view, for antihypertensive therapy during the acute phase of stroke (i.e. concurrent hypertensive encephalopathy or aortic dissection, or other situations)
• Other serious or life-threatening disease before the stroke: • patient severely mentally or physically disabled (e.g. Mini Mental Status score < 20, or modified Rankin Scale score ≥ 4) • life expectancy < 12 months
• Patient unavailable for follow-up (e.g. no fixed address)
• Pregnant or breast-feeding woman

Please refer to this study by ClinicalTrials.gov identifier  NCT00120003

Eivind Berge, MD, PhD      +47 22 11 91 01    eivind.berge@medisin.uio.no
Rune Aakvik, MD      +47 23 01 66 60    rune.aakvik@medisin.uio.no

Norway
      Ullevaal University Hospital, Oslo,  N-0407,  Norway; Recruiting

Study chairs or principal investigators

Eivind Berge, MD, PhD,  Principal Investigator,  Ullevaal University Hospital   
Per Morten Sandset, Prof,  Study Chair,  Ullevaal University Hospital   
Povel Paus, MD, PhD,  Study Director,  Ullevaal University Hospital   

Study ID Numbers:  050321
Record last reviewed:  July 2005
Last Updated:  July 18, 2005
Record first received:  July 14, 2005
ClinicalTrials.gov Identifier:  NCT00120003
Health Authority: Norway: Norwegian Medicines Agency; Sweden: Medical Products Agency; Denmark: Danish Medicines Agency
ClinicalTrials.gov processed this record on 2005-07-26