The Efficacy of Nitric Oxide in Stroke (ENOS) Trial (ENOS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00989716
Recruitment Status : Unknown
Verified July 2012 by University of Nottingham.
Recruitment status was:  Recruiting
First Posted : October 5, 2009
Last Update Posted : July 24, 2012
Information provided by (Responsible Party):
University of Nottingham

Brief 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. 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).

Condition or disease Intervention/treatment Phase
Stroke Drug: Transdermal glyceryl trinitrate patch Drug: Pre-stroke antihypertensives Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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
Study Start Date : July 2001
Estimated Primary Completion Date : October 2013
Estimated Study Completion Date : October 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Glyceryl trinitrate transdermal patch Drug: Transdermal glyceryl trinitrate patch
5mg per day
Other Name: Local ward stock to be used.

Experimental: Continue or stop pre-stroke antihypertensives Drug: Pre-stroke antihypertensives
Continue or stop pre-stroke anti-hypertensives

Primary Outcome Measures :
  1. Reduced death or dependency (modified Rankin score) [ Time Frame: 90 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00989716

Contact: Philip Bath

United Kingdom
Nottingham University Hospitals NHS Trust (City Hospital) Recruiting
Nottingham, Nottinghamshire, United Kingdom, NG5 1PJ
Sponsors and Collaborators
University of Nottingham
Principal Investigator: Philip Bath University of Nottingham

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of Nottingham Identifier: NCT00989716     History of Changes
Other Study ID Numbers: 04002
EudraCT no: 2004-003870-27
First Posted: October 5, 2009    Key Record Dates
Last Update Posted: July 24, 2012
Last Verified: July 2012

Additional relevant MeSH terms:
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Nitric Oxide
Antihypertensive Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Protective Agents