Cerebrovascular AccidentPhase 4NCT00108706
Acute Candesartan Cilexetil Outcomes Stroke Trial (ACCOST)
A Phase 4 study testing Candesartan in people with Cerebrovascular Accident and Acute Stroke, run by City Hospitals Sunderland NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The aim of this study is to determine whether it is safe and effective to give the Angiotensin Receptor Blocker (ARB) Candesartan within the first 72 hours following acute stroke. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebrovascular Accident, Acute Stroke
- What is being tested?
- Candesartan
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2004to Sep 2007
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute ischaemic stroke <72 hours from symptom onset (CT proven)
- Medically stable with no evidence of acute infection and not receiving antibiotic therapy
- Neurologically stable (no progression on NIHSS)
- Able to swallow unthickened fluids safely
- Mean BP (blood pressure) >120/70 in unaffected arm
Who cannot join
- Previous severe disability (Modified Rankin Score >2)
- Nursing home residents
- Previous history of congestive heart failure requiring treatment with ACE-Inhibitors or angiotensin receptor blockers
- Renal impairment (creatinine >200 mcgmol/L)
- Women of child bearing potential
- Minors <18 years of age
- History of dementia without ability to consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Sunderland Royal Hospital
Sunderland, Tyne and Wear, SR4 7TP
About this study
The aim of this study is to determine whether it is safe and effective to give the Angiotensin Receptor Blocker (ARB) Candesartan within the first 72 hours following acute stroke.
Read the detailed description
Lowering blood pressure reduces the risk of first ever and recurrent stroke. There is extensive evidence that blood pressure should be lowered following acute stroke, even from so called normal levels. However, it is not clear how soon after acute stroke that blood pressure should be lowered. Observational studies have demonstrated increased mortality with both high and low blood pressure. The optimal management of blood pressure in the immediate post-stroke period remains controversial.
Although uncertainty exists with regard to lowering blood pressure in the acute stages of stroke, two large randomised controlled trials have demonstrated unequivocally that intense management of blood pressure started >4 weeks from the onset of stroke significantly reduces the risk of recurrent stroke. Both of these trials have used an Angiotensin Converting Enzyme Inhibitor (ACE-I) based regime. It has been proposed that these benefits may be due to a direct result of the ACE-I rather than blood pressure lowering per se. Similar vasculoprotective effects have been seen in ARBs, but evidence of their safety and efficacy in acute stroke is limited to those patients with the highest blood pressures (>200/110). The trial (ACCESS) was terminated prematurely due to a positive imbalance in favour of intervention with the ARB Candesartan. If such interventions are to convey potential benefit they need to be started as soon as possible following the acute event in order that the ischaemic cascade which leads to neuronal death may be modified. Further research is first required in order to demonstrate their safety and efficacy when used in this way.
ACCOST is a two phase randomised controlled trial designed to address this important research question. Phase I is a four week double blind placebo controlled phase where patients receive either Candesartan 4 mg daily or matched placebo, with no blood pressure treatment target. A treatment titration step occurs after two weeks where, subject to titration criteria, subjects will receive either Candesartan 8 mg daily or matched placebo. After the first four weeks, the subjects are unblinded and enter Phase II of the trial. Phase II is an eight week open label comparison of Candesartan and 'usual care' with an ACE-I based treatment regime. Blood pressure is now treated to reach the British Hypertension Society target blood pressure of <140/85, with or without additional therapy.
Blinded outcome measures will include neurological recovery based on the National Institutes of Health Stroke Scale, as well as functional recovery. Incidence of first dose hypotension and changes in renal function will also be collected.
- Conditions
- Cerebrovascular Accident, Acute Stroke
- Being tested
- Candesartan
- Keywords
- Acute Stroke, Cerebrovascular Accident, Ischaemic Stroke, Candesartan, Angiotensin Receptor Blocker
- Medical subject headings
- Stroke, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CandesartanDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality (all causes)
Mortality (vascular causes)
Secondary outcomes (2)
Neurological Recovery (NIHSS [National Institutes of Health Stroke Scale])
Functional Recovery (Modified Rankin/Barthel)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2005 (estimated)
- Study startDec 2004
- Study completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cerebrovascular AccidentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 50 participants
Sponsor and investigators
- Lead sponsor
- City Hospitals Sunderland NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Investigators
- Christopher S Gray, MD, Principal investigator, University of Newcastle Upon-Tyne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00108706
- Sponsor's protocol ID
- ACCOST
- Other IDs
- CTA Number:21763/0001/001, EudraCT Number:2004-001847-31
- Status last verified
- Sep 2006
- First submitted
- 18 Apr 2005
- Last updated
- 13 Sep 2006
- Results posted
- No
Publications
Heart Outcomes Prevention Evaluation Study Investigators; Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53. doi: 10.1056/NEJM200001203420301.
PubMed 10639539PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001 Sep 29;358(9287):1033-41. doi: 10.1016/S0140-6736(01)06178-5.
PubMed 11589932Schrader J, Luders S, Kulschewski A, Berger J, Zidek W, Treib J, Einhaupl K, Diener HC, Dominiak P; Acute Candesartan Cilexetil Therapy in Stroke Survivors Study Group. The ACCESS Study: evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors. Stroke. 2003 Jul;34(7):1699-703. doi: 10.1161/01.STR.0000075777.18006.89. Epub 2003 Jun 19.
PubMed 12817109
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Candesartan Cilexetil Outcomes Stroke Trial (ACCOST)
- ClinicalTrials.gov ID
- NCT00108706
- Acronym / sponsor ID
- ACCOST
- Conditions
- Cerebrovascular Accident, Acute Stroke
- Keywords
- Acute Stroke, Cerebrovascular Accident, Ischaemic Stroke, Candesartan, Angiotensin Receptor Blocker
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants
- Lead sponsor
- City Hospitals Sunderland NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- Dec 2004
- Study completion
- Sep 2007
- First posted
- 19 Apr 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to determine whether it is safe and effective to give the Angiotensin Receptor Blocker (ARB) Candesartan within the first 72 hours following acute stroke.
Detailed description
Lowering blood pressure reduces the risk of first ever and recurrent stroke. There is extensive evidence that blood pressure should be lowered following acute stroke, even from so called normal levels. However, it is not clear how soon after acute stroke that blood pressure should be lowered. Observational studies have demonstrated increased mortality with both high and low blood pressure. The optimal management of blood pressure in the immediate post-stroke period remains controversial.
Although uncertainty exists with regard to lowering blood pressure in the acute stages of stroke, two large randomised controlled trials have demonstrated unequivocally that intense management of blood pressure started >4 weeks from the onset of stroke significantly reduces the risk of recurrent stroke. Both of these trials have used an Angiotensin Converting Enzyme Inhibitor (ACE-I) based regime. It has been proposed that these benefits may be due to a direct result of the ACE-I rather than blood pressure lowering per se. Similar vasculoprotective effects have been seen in ARBs, but evidence of their safety and efficacy in acute stroke is limited to those patients with the highest blood pressures (>200/110). The trial (ACCESS) was terminated prematurely due to a positive imbalance in favour of intervention with the ARB Candesartan. If such interventions are to convey potential benefit they need to be started as soon as possible following the acute event in order that the ischaemic cascade which leads to neuronal death may be modified. Further research is first required in order to demonstrate their safety and efficacy when used in this way.
ACCOST is a two phase randomised controlled trial designed to address this important research question. Phase I is a four week double blind placebo controlled phase where patients receive either Candesartan 4 mg daily or matched placebo, with no blood pressure treatment target. A treatment titration step occurs after two weeks where, subject to titration criteria, subjects will receive either Candesartan 8 mg daily or matched placebo. After the first four weeks, the subjects are unblinded and enter Phase II of the trial. Phase II is an eight week open label comparison of Candesartan and 'usual care' with an ACE-I based treatment regime. Blood pressure is now treated to reach the British Hypertension Society target blood pressure of <140/85, with or without additional therapy.
Blinded outcome measures will include neurological recovery based on the National Institutes of Health Stroke Scale, as well as functional recovery. Incidence of first dose hypotension and changes in renal function will also be collected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Acute ischaemic stroke <72 hours from symptom onset (CT proven)
- Medically stable with no evidence of acute infection and not receiving antibiotic therapy
- Neurologically stable (no progression on NIHSS)
- Able to swallow unthickened fluids safely
- Mean BP (blood pressure) >120/70 in unaffected arm
Key exclusion criteria (7 listed)
- Previous severe disability (Modified Rankin Score >2)
- Nursing home residents
- Previous history of congestive heart failure requiring treatment with ACE-Inhibitors or angiotensin receptor blockers
- Renal impairment (creatinine >200 mcgmol/L)
- Women of child bearing potential
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Candesartan | Drug | – |
Primary outcome
Mortality (all causes)
Mortality (vascular causes)
2 secondary outcomes
Neurological Recovery (NIHSS [National Institutes of Health Stroke Scale])
Functional Recovery (Modified Rankin/Barthel)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2006.
- Background: PubMed 10639539Heart Outcomes Prevention Evaluation Study Investigators; Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53. doi: 10.1056/NEJM200001203420301.
- Background: PubMed 11589932PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001 Sep 29;358(9287):1033-41. doi: 10.1016/S0140-6736(01)06178-5.
- Background: PubMed 12817109Schrader J, Luders S, Kulschewski A, Berger J, Zidek W, Treib J, Einhaupl K, Diener HC, Dominiak P; Acute Candesartan Cilexetil Therapy in Stroke Survivors Study Group. The ACCESS Study: evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors. Stroke. 2003 Jul;34(7):1699-703. doi: 10.1161/01.STR.0000075777.18006.89. Epub 2003 Jun 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher S Gray, MD principal investigator
University of Newcastle Upon-Tyne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Candesartan in people with Cerebrovascular Accident and Acute Stroke, run by City Hospitals Sunderland NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Sep 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (all causes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00108706, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2006.