The Efficacy of Nitric Oxide in Stroke (ENOS) Trial

NCT ID: NCT00989716

Last Updated: 2012-07-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

3500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-07-31

Study Completion Date

2013-10-31

Brief Summary

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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:

1. The safety and efficacy of nitric oxide, given as transdermal glyceryl trinitrate.
2. 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).

Detailed Description

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Conditions

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Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Glyceryl trinitrate transdermal patch

Group Type ACTIVE_COMPARATOR

Transdermal glyceryl trinitrate patch

Intervention Type DRUG

5mg per day

Continue or stop pre-stroke antihypertensives

Group Type EXPERIMENTAL

Pre-stroke antihypertensives

Intervention Type DRUG

Continue or stop pre-stroke anti-hypertensives

Interventions

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Transdermal glyceryl trinitrate patch

5mg per day

Intervention Type DRUG

Pre-stroke antihypertensives

Continue or stop pre-stroke anti-hypertensives

Intervention Type DRUG

Other Intervention Names

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Local ward stock to be used.

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 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. -
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Nottingham

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Philip Bath

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Locations

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Nottingham University Hospitals NHS Trust (City Hospital)

Nottingham, Nottinghamshire, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Philip Bath

Role: CONTACT

Email: [email protected]

References

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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.

Reference Type DERIVED
PMID: 28752410 (View on PubMed)

Woodhouse 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.

Reference Type DERIVED
PMID: 26463698 (View on PubMed)

Related Links

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Other Identifiers

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ISRCTN99414122

Identifier Type: -

Identifier Source: secondary_id

EudraCT no: 2004-003870-27

Identifier Type: -

Identifier Source: secondary_id

04002

Identifier Type: -

Identifier Source: org_study_id