StrokePhase 3ENOSNCT00989716
The Efficacy of Nitric Oxide in Stroke (ENOS) Trial
A Phase 3 study testing Transdermal glyceryl trinitrate patch and Pre-stroke antihypertensives in people with Stroke, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
Nitric oxide is a multimodal candidate treatment for acute stroke having a number of properties which may be beneficial in acute stroke, including lowering blood pressure, causing cerebral vasodilation, and improving central and systemic haemodynamics. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Transdermal glyceryl trinitrate patch and Pre-stroke antihypertensives
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,500 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2001to Oct 2013
- Phase
- Phase 3
- 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
- Adult(> 18 yrs).
- Clinical stroke syndrome with limb weakness lasting at least 1 hour i.e. not likely to be a transient ischaemic attack).
- Limb weakness (SNSS Arm <6 and/or Leg <6).
- Onset < 48 hours.
- Conscious (Glasgow Coma Scale > 8).
- Independent prior to stroke (pre-morbid Rankin scale < 2).
- Meaningful consent, or assent from a relative or carer
Who cannot join
- Definite need for nitrate therapy
- Contraindication to nitrate therapy
- Definite need for prior antihypertensive or anti-anginal medication
- Definite need for antihypertensive therapy during acute stroke
- Systolic blood pressure <140 mmHg or >220 mmHg.
- Patients expected to require surgical intervention
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- Known intracerebral pathology other than stroke
- Other serious condition which is likely to prevent outcome assessment at 3 months
- Previous enrollment in ENOS or current involvement in another trial of an experimental drug intervention.
- Not available for follow-up -Females of childbearing potential, pregnancy or breastfeeding. -
Trial locations and contacts
1 site in 1 country.
Philip Bath contact
United Kingdom1 site, 1 recruiting
- Recruiting
Nottingham University Hospitals NHS Trust (City Hospital)
Nottingham, Nottinghamshire, NG5 1PJ
About this study
Official title: A Prospective, Collaborative, International, Multicentre, Randomised, Parallel-group, Single and Outcome Blinded, Controlled, Factorial Trial to Investigate the Safety and Efficacy of Treatment With Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, and of Continuing or Stopping Temporarily Pre-stroke Antihypertensive Therapy, in Patients With Acute Stroke
Nitric oxide is a multimodal candidate treatment for acute stroke having a number of properties which may be beneficial in acute stroke, including lowering blood pressure, causing cerebral vasodilation, and improving central and systemic haemodynamics. Nitric oxide donors are effective in experimental stroke and pilot studies in patients suggest that one, glyceryl trinitrate, can be delivered easily in a transdermal preparation. Around half of all patients admitted with acute stroke are taking antihypertensive therapy immediately prior to their stroke. No data exist as to whether it is beneficial or safe to stop or continue this treatment during the acute phase. ENOS is a prospective, international, multicentre, randomised, parallel-group, blinded, controlled, collaborative, factorial trial designed to test two questions related to the management of blood pressure immediately post-stroke:
- The safety and efficacy of nitric oxide, given as transdermal glyceryl trinitrate.
- The safety and efficacy of stopping or continuing prior antihypertensive medication.
Previously independent adult patients who are conscious and have residual limb weakness are eligible for enrollment. Central randomisation will be performed via the internet. Treatment is initiated within 48 hours of stroke onset and is given as daily glyceryl trinitrate patches for 7 days. A computed tomography (CT) scan is required within 7 days of randomisation. Early follow-up is performed locally over the 7 days of treatment, including blood pressure, early stroke events, and adverse events. Telephone central follow-up by the trial co-ordinating centre will be performed at 3 months. The primary outcome is combined death or dependency (modified Rankin Score >2).
- Conditions
- Stroke
- Being tested
- Transdermal glyceryl trinitrate patch, Pre-stroke antihypertensives
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transdermal glyceryl trinitrate patchDrug
Also called Local ward stock to be used.
5mg per day
Pre-stroke antihypertensivesDrug
Continue or stop pre-stroke anti-hypertensives
| Study group | Role | What they receive |
|---|---|---|
| Glyceryl trinitrate transdermal patch | Active comparator | Not described Receives: Drug: Transdermal glyceryl trinitrate patch |
| Continue or stop pre-stroke antihypertensives | Experimental | Not described Receives: Drug: Pre-stroke antihypertensives |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduced death or dependency (modified Rankin score)
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2009 (estimated)
- Study startJul 2001
- Primary completionOct 2013 (estimated)
- Study completionOct 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 3,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philip Bath, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00989716
- Sponsor's protocol ID
- 04002
- Other IDs
- ISRCTN99414122, EudraCT no: 2004-003870-27
- Acronym
- ENOS
- Status last verified
- Jul 2012
- First submitted
- 2 Oct 2009
- Last updated
- 24 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Learoyd AE, Woodhouse L, Shaw L, Sprigg N, Bereczki D, Berge E, Caso V, Christensen H, Collins R, Czlonkowska A, El Etribi A, Farr TD, Gommans J, Laska AC, Ntaios G, Ozturk S, Pocock SJ, Prasad K, Wardlaw JM, Fone KC, Bath PM, Trueman RC; ENOS Trial investigators. Infections Up to 76 Days After Stroke Increase Disability and Death. Transl Stroke Res. 2017 Dec;8(6):541-548. doi: 10.1007/s12975-017-0553-3. Epub 2017 Jul 27.
PubMed 28752410Woodhouse L, Scutt P, Krishnan K, Berge E, Gommans J, Ntaios G, Wardlaw J, Sprigg N, Bath PM; ENOS Investigators. Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke: Subgroup Analysis of the Efficacy of Nitric Oxide in Stroke (ENOS) Trial. Stroke. 2015 Nov;46(11):3194-201. doi: 10.1161/STROKEAHA.115.009647. Epub 2015 Oct 13.
PubMed 26463698
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Collaborative, International, Multicentre, Randomised, Parallel-group, Single and Outcome Blinded, Controlled, Factorial Trial to Investigate the Safety and Efficacy of Treatment With Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, and of Continuing or Stopping Temporarily Pre-stroke Antihypertensive Therapy, in Patients With Acute Stroke
- ClinicalTrials.gov ID
- NCT00989716
- Acronym / sponsor ID
- ENOS / 04002
- Conditions
- Stroke
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 3,500 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Jul 2001
- Primary completion
- Oct 2013 (estimated)
- Study completion
- Oct 2013 (estimated)
- First posted
- 5 Oct 2009 (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.
Nitric oxide is a multimodal candidate treatment for acute stroke having a number of properties which may be beneficial in acute stroke, including lowering blood pressure, causing cerebral vasodilation, and improving central and systemic haemodynamics. Nitric oxide donors are effective in experimental stroke and pilot studies in patients suggest that one, glyceryl trinitrate, can be delivered easily in a transdermal preparation. Around half of all patients admitted with acute stroke are taking antihypertensive therapy immediately prior to their stroke. No data exist as to whether it is beneficial or safe to stop or continue this treatment during the acute phase. ENOS is a prospective, international, multicentre, randomised, parallel-group, blinded, controlled, collaborative, factorial trial designed to test two questions related to the management of blood pressure immediately post-stroke:
- The safety and efficacy of nitric oxide, given as transdermal glyceryl trinitrate.
- The safety and efficacy of stopping or continuing prior antihypertensive medication.
Previously independent adult patients who are conscious and have residual limb weakness are eligible for enrollment. Central randomisation will be performed via the internet. Treatment is initiated within 48 hours of stroke onset and is given as daily glyceryl trinitrate patches for 7 days. A computed tomography (CT) scan is required within 7 days of randomisation. Early follow-up is performed locally over the 7 days of treatment, including blood pressure, early stroke events, and adverse events. Telephone central follow-up by the trial co-ordinating centre will be performed at 3 months. The primary outcome is combined death or dependency (modified Rankin Score >2).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glyceryl trinitrate transdermal patch | Active comparator | Drug: Transdermal glyceryl trinitrate patch |
| Continue or stop pre-stroke antihypertensives | Experimental | Drug: Pre-stroke antihypertensives |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult(> 18 yrs).
- Clinical stroke syndrome with limb weakness lasting at least 1 hour i.e. not likely to be a transient ischaemic attack).
- Limb weakness (SNSS Arm <6 and/or Leg <6).
- Onset < 48 hours.
- Conscious (Glasgow Coma Scale > 8).
Key exclusion criteria (10 listed)
- Definite need for nitrate therapy
- Contraindication to nitrate therapy
- Definite need for prior antihypertensive or anti-anginal medication
- Definite need for antihypertensive therapy during acute stroke
- Systolic blood pressure <140 mmHg or >220 mmHg.
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 |
|---|---|---|
| Transdermal glyceryl trinitrate patchAlso: Local ward stock to be used.5mg per day | Drug | Glyceryl trinitrate transdermal patch |
| Pre-stroke antihypertensivesContinue or stop pre-stroke anti-hypertensives | Drug | Continue or stop pre-stroke antihypertensives |
Primary outcome
Reduced death or dependency (modified Rankin score)
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2012.
- Derived from this study: PubMed 28752410Learoyd AE, Woodhouse L, Shaw L, Sprigg N, Bereczki D, Berge E, Caso V, Christensen H, Collins R, Czlonkowska A, El Etribi A, Farr TD, Gommans J, Laska AC, Ntaios G, Ozturk S, Pocock SJ, Prasad K, Wardlaw JM, Fone KC, Bath PM, Trueman RC; ENOS Trial investigators. Infections Up to 76 Days After Stroke Increase Disability and Death. Transl Stroke Res. 2017 Dec;8(6):541-548. doi: 10.1007/s12975-017-0553-3. Epub 2017 Jul 27.
- Derived from this study: PubMed 26463698Woodhouse L, Scutt P, Krishnan K, Berge E, Gommans J, Ntaios G, Wardlaw J, Sprigg N, Bath PM; ENOS Investigators. Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke: Subgroup Analysis of the Efficacy of Nitric Oxide in Stroke (ENOS) Trial. Stroke. 2015 Nov;46(11):3194-201. doi: 10.1161/STROKEAHA.115.009647. Epub 2015 Oct 13.
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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.
Philip Bath contact
Philip Bath principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Transdermal glyceryl trinitrate patch and Pre-stroke antihypertensives in people with Stroke, run by University of Nottingham 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 7 inclusion and 10 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 24 Jul 2012. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Philip Bath (philip.bath@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduced death or dependency (modified Rankin score) (time frame: 90 days). 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 NCT00989716, which also lists 2 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 24 Jul 2012.