Efficacy of Nitric Oxide in Stroke trial
ENOS
The 'Efficacy of Nitric Oxide in Stroke' (ENOS) study is a collaborative, international, multicentre, prospective, randomised, single-blind, blinded endpoint, parallel-group, controlled trial designed to test the safety and efficacy of:
(i) transdermal glyceryl trinitrate (a nitric oxide donor) or control; and
(ii) continuing or temporarily stopping prior anti-hypertensive medication.
5,000 patients with acute ischaemic or haemorrhagic stroke will be enrolled within 48 hours of the onset of stroke and treatment will be given for 7 days. The primary outcome is death or dependency (modified Rankin Scale >2) and will be determined at 90 days by observers blinded to treatment.
Power point presentation, V1.0 (Powerpoint, size=3.9MB)
Brief Information for patients & relatives about the trial, V1.1 (PDF file, MREC approved)
Full information for patients, V2.11 (PDF file, MREC approved)
ENOS trial
Enter ENOS trial web-site
Status
As of 22 July 2010:
Enrolled patients: 1,922 with 941 (49%) in continue vs. stop pre-stroke antihypertensive therapy (see logon page for the very latest figure)
Centres who have recruited one or more patients: 107
Countries who have recruited one or more patients: 17 - Australia, Canada, China, Egypt, Eire, Hong Kong, India, Italy, Malaysia, New Zealand, Philippines, Poland, Romania, Singapore, Spain, Sri Lanka, UK
Continents who have enrolled one or more patients: 5 - Africa, Asia, Australia-Oceania, Europe, North America
Funding
Forthcoming events
News
- July 2010: Congratulations to all - ENOS reaches 1,900 patients.
- June 2010: Congratulations to Dr Valeria Caso in Perugia for recruiting the first ENOS patient in Italy. Dr Caso is the National Coordinator.
- June 2010: Data Monitoring Committee recommend trial continues unchanged.
- May 2010: Congratulations to all - ENOS reaches 1,800 patients.
- February 2010: Congratulations to all - ENOS reaches 1,700 patients.
- December 2009: Congratulations to all - ENOS reaches 1,600 patients.
- November 2009: Following their latest review of the data, the Data Monitoring Committee (PDF file) recommend that the trial should continue.
- November 2009: Congratulations to all - ENOS reaches 1,500 patients.
- August 2009: Congratulations to all - ENOS reaches 1,400 patients.
- August 2009: Congratulations to Dr Ronan Collins in Dublin for recruiting the first ENOS patient in Eire. Dr Collins is the National Coordinator.
- June 2009: Congratulations to all - ENOS makes 1,300 patients.
- May 2009: Following their latest review of the data, the Data Monitoring Committee (PDF file) recommend that the trial should continue.
- April 2009: Congratulations to Professor Exuperio Tejedor in Madrid for recruiting the first ENOS patient in Spain. Professor Tejedor is the National Coordinator.
- March 2009: Congratulations to Professor Szabolcs Szatmari in Targu Mures for recruiting the first ENOS patient in Romania. Professor Szatmari is the National Coordinator.
- March 2009: Congratulations to Professor Anwar Etribi in Cairo for recruiting the first ENOS patient in Egypt. Professor Etribi is the National Coordinator. Start-up of the trial in Egypt means that ENOS is now operating in 5 continents!
- March 2009: Congratulations to all - ENOS makes 1,200 patients. Thanks to all who have contributed to this great success.
- January 2009: Apologies but the earlier comment that January was the highest recruiting month ever in ENOS was incorrect. However, 31 patients were enrolled into the trial which is still very credible.
- December 2008: Following their latest review of the data, the Data Monitoring Committee (PDF file) recommend that the trial should continue.
- December 2008: Excellent news - ENOS makes 1100 patients. Thanks to all the patients and investigators who have contributed to this important milestone.
- October 2008: ENOS has its highest recruiting month ever at 34 patients. Thanks to all the investigators who have made it possible, and especially those who are managing to enrol more than one patient per month: AIIMS/New Delhi, India; Blackpool, UK; Derby, UK; Dunedin, New Zealand; Kirkcaldy, UK; .
- August 2008: Fantastic news - ENOS makes 1000 patients. Thanks to all who have contributed to this massive endeavour: investigators, patients and staff. And now for the second 1000 - good luck!
- August 2008: Congratulations to Prof Prasad and colleagues (AIIMS, Delhi) for enrolling the first ENOS patient in India. Prof Prasad is also the National Coordinator for India.
- May 2008: Many thanks to all the investigators and potential investigators who attended the ENOS Stand and Investigator meeting at the European Stroke Conference in Nice.
- April 2008: Congratulations to all the investigators - ENOS reaches 900 patients.
- April 2008: Many thanks to all the potential investigators who attended the ENOS Investigator meeting at the V International Ischaemic Stroke Workshop in Madrid.
- January 2008: The updated protocol and associated documents have been approved by MREC (National Ethics) and the MHRA (competent authority) in the UK. This brings the trial right up to date in approvals. The approvals documents are mounted on the Investigator website.
- December 2007: Well done to United Lincolnshire Hospitals who recruited 10 patients between 1 November and end December and won GBP 500.
- December 2007: Following their latest review of the data for 795 patients, the Data Monitoring Committee (PDF file) recommend that the trial should continue.
- December 2007: Thanks to all the current and potential Investigators who attended the ENOS stand at 2nd UK Stroke Forum (UKSF) in Harrogate.
- November 2007: Congratulations to all the investigators - ENOS reaches 800 patients. And special thanks to Yeovil District Hospital who found the 800th patient - they have a free registration to attend The European Stroke Conference in Nice in May 2008.
- June 2007: Congratulations to all the investigators - ENOS reaches 700 patients.
- May 2007: Thanks to all the Investigators who attended the ENOS meeting and/or stand at the European Stroke Conference in Glasgow.
- March 2007: Congratulations to all investigators - ENOS reaches 600 patients. And thanks to Stepping Hill, Stockport in the UK for making it 600!
- February 2007: We are very pleased to welcome Dr Graham Venables as the incoming independent Chairman of the Trial Steering Committee.
- January 2007: The Stroke exemplar within the MRC NeuroGRID project, which comprises ENOS and IST-3, has been published in the International Journal of Stroke (February 2007, volume 2, issue 1)
- January 2007: Annual Trial Steering Committee (TSC) held. We would like to thank Professor Daffyd Thomas, who has recently retired, for guiding us from the begining of the trial as the independent Chairman of the TSC. Daffyd has always been very supportive and we wish him well in retirement. Daffyd will remain as Chair until we appoint successor.
- December 2006: Congratulations to all the investigators - ENOS reaches 550 patients.
- December 2006: Following their latest review of the data for 520 patients, the Data Monitoring Committee (PDF file) recommend that the trial should continue.
- December 2006: ENOS has its own stand at The UK Stroke Forum (in Harrogate)
- November 2006: Main phase of trial commences!
- October 2006: Trial protocol is published in International Journal of Stroke (November 2006, volume 1, issue 4)
- August 2006: Congratulations to all the investigators - ENOS reaches 500 patients. And thanks to Singapore for making it 500!
- June 2006: Congratulations to Dr Jayathissa and colleagues (Hutt Valley) for enrolling the first ENOS patient in New Zeland. Dr John Gommans (Hawkes Bay) is the National Coordinator.
- May 2006: Media coverage of trial: UK Saga FM Radio
- April 2006: UK Stroke Research Network (UKSRN) 'adopts' ENOS. Also see UK Clinical Research Network (UKCRN)
- April 2006: Congratulations to Professor L Wong and colleagues for enrolling the first ENOS patient in Hong Kong
- April 2006: Medical Research Council funds the main phase of ENOS which will commence in September 2006. Congratulations to all the Investigators for supporting the trial without which this funding would not have been made
- Feb 2006: First Belgium site (Leige, Dr Desfontaines) joins trial
- Dec 2005: Congratulations to Professor Y-Y Wang, Dr X Gong and colleagues for enrolling the first ENOS patient in China
- Dec 2005: Please note new contact telephone and fax numbers
- Nov 2005: New Zealand Stroke Trials Network (NZSTN) review and approve ENOS, and recommend it to their sites
- Oct 2005: Congratulations to all the investigators - ENOS passes 400 patients
- Oct 2005: Thanks to BUPA Foundation who have extended the trial's start-up funding for up to 5 months to August 2006
- Summer 2005: Media coverage: Queen's Medical Centre
- May 2005: Congratulations to Professor C Bladin and colleagues for enrolling the first 2 ENOS patients in Australia
- Apr 2005: Congratulations to all the investigators - Now the largest ever randomised controlled trial to assess blood pressure management in acute stroke
- Feb 2005: Australia joins ENOS
- Jan 2005: Congratulations to Dr C Chen and colleagues in Singapore for being funded by A*STAR for the ENOS MRI sub-study
- Dec 2004: Congratulations to all the investigators - ENOS passes 300 patients
- Aug 2004: Medical Research Council (MRC) funds NeuroGRID. ENOS is an exemplar project within NeuroGRID
- Feb 2004: Media coverage of trial: BBC News, Medical News Today, UK Saga FM Radio
- Dec 2003: UK BUPA Foundation funds ENOS start-up phase for 400 patients
- Oct 2003: Canadian Stroke Consortium (CSC) review and approve ENOS, and recommend it to their sites
- Sep 2003: Australasian Stroke Trials Network (ASTN) review and approve ENOS, and recommend it to their sites
- Jun 2003: Now bigger than all the existing randomised data for nitric oxide donors in acute stroke
- Mar 2003: Now the largest trial of a nitric oxide donor in acute stroke
ENOS trial
Enter ENOS trial web-site
Documents
ENOS protocol - summary, V1.7 (html file) **UPDATED**
Expression of interest, V1.1 (PDF file)
Newsletter 54 - June 2010 (PDF file)
Newsletter 53 - April 2010 (PDF file)
Newsletter 52 - February 2010 (PDF file)
Newsletter 51 - December 2009 (PDF file)
Newsletter 50 - October 2009 (PDF file)
Newsletter 49 - August 2009 (PDF file)
Newsletter 48 - June 2009 (PDF file)
Newsletter 47 - April 2009 (PDF file)
Newsletter 46 - February 2009 (PDF file)
Newsletter 45 - December 2008 (PDF file)
Newsletter 44 - October 2008 (PDF file)
Newsletter 43 - August 2008 (PDF file)
Newsletter 42 - June 2008 (PDF file)
Newsletter 41 - April 2008 (PDF file)
Newsletter 40 - February 2008 (PDF file)
Newsletter 39 - December 2007 (PDF file)
Newsletter 38 - October 2007 (PDF file)
Newsletter 37 - August 2007 (PDF file)
Newsletter 36 - June 2007 (PDF file)
Newsletter 35 - April 2007 (PDF file)
Newsletter 34 - February 2007 (PDF file)
Newsletter 33 - December 2006 (PDF file)
Newsletter 32 - October 2006 (PDF file)
Newsletter 31 - August 2006 (PDF file)
Newsletter 30 - June 2006 (PDF file)
Newsletter 29 - April 2006 (PDF file)
Newsletter 28 - February 2006 (PDF file)
MRI study newsletter - December 2005 (PDF file)
Newsletter 27 - December 2005 (PDF file)
Newsletter 26 - October 2005 (PDF file)
Newsletter 25 - August 2005 (PDF file)
Newsletter 24 - June 2005 (PDF file)
Newsletter 23 - April 2005 (PDF file)
Newsletter 22 - February 2005 (PDF file)
Newsletter 21 - December 2004 (PDF file)
Newsletter 20 - October 2004 (PDF file)
Newsletter 19 - August 2004 (PDF file)
Newsletter 18 - June 2004 (PDF file)
Newsletter 17 - April 2004 (PDF file)
Newsletter 16 - February 2004 (PDF file)
Newsletter 15 - December 2003 (PDF file)
Newsletter 14 - October 2003 (PDF file)
Newsletter 13 - August 2003 (PDF file)
Newsletter 12 - June 2003 (PDF file)
Newsletter 11 - April 2003 (PDF file)
Newsletter 10 - February 2003 (PDF file)
Newsletter 9 - December 2002 (PDF file)
Newsletter 8 - October 2002 (PDF file)
Newsletter 7 - August 2002 (PDF file)
Newsletter 6 - June 2002 (PDF file)
Newsletter 5 - April 2002 (PDF file)
Newsletter 4 - February 2002 (PDF file)
Newsletter 3 - November 2001 (PDF file)
Newsletter 2 - September 2001 (PDF file)
Newsletter 1 - July 2001 (PDF file)
Presentations/publications/listings
ENOS has been presented regularly at stroke conferences since 2001, including:
Recent attendances include:
- July 2010 - NIHR Stroke Research Network Annual Conference, Newcastle, UK
- May 2010 - European Stroke Conference, Barcelona, Spain
- February 2010 - International Stroke Conference/American Stroke Association, San Antonio, USA
- January 2010 - West Midlands Stroke Research Netowrk, Birmingham, UK
- December 2009 - UK Stroke Forum, Glasgow, UK
- July 2009 - UK Stroke Research Network Annual Conference, Newcastle, UK
- May 2009 - European Stroke Conference, Stockholm, Sweden
- May 2009 - Peninsula Stroke Research Network Annual Conference, Exeter, UK
- February 2009 - International Stroke Conference/American Stroke Association, San Diego, USA
- December 2008 - 3rd UK Stroke Forum (UKSF) in Harrogate, UK.
- October 2008 - 56th Irish Gerontological Society Scientific meeting in Kilkenny, Eire.
- October 2008 - Northern Ireland Multidisciplinary Association for Stroke Teams meeting.
- October 2008 - Scottish Stroke Research Network meeting.
- October 2008 - 12th Asian Oceanian Congress of Neurology (AOCN 2008)/16th Annual Conference of Indian Academy of Neurology (IAN) in New Delhi, India.
Trial protocol:
- The ENOS Trial Investigators. Glyceryl trinitrate vs. control, and continuing vs. stopping temporarily prior antihypertensive therapy, in acute stroke: rationale and design of the Efficacy of Nitric Oxide in Stroke (ENOS) trial (ISRCTN99414122). International J Stroke 2006;1:245-249
Other selected presentations, publications and listings include:
- Is lowering blood pressure hazardous in patients with significant ipsilateral carotid stenosis and acute ischaemic stroke? Interim assessment in the 'Efficacy of Nitric Oxide in Stroke' Trial. Blood Pressure Monitoring 2009;14(1):20-25
- The NeuroGrid stroke exemplar clinical trial protocol. International Journal of Stroke 2007;2:63-69
- Effect of nitric oxide donors on blood pressure and pulse pressure in acute and subacute stroke. J Stroke Cerebrovascular Diseases 2006;15:245-249
- Continuing prior antihypertensive medication in acute stroke lowers blood pressure: Data from the continue vs stop arm of the 'Efficacy of Nitric Oxide in Stroke' (ENOS) trial. World Congress of Neurology, Sydney, November 2005
- ENOS Efficacy of Nitric Oxide in Stroke Trial. Stroke Center Stroke Trials Registry 2002
- Management of blood pressure in acute stroke. Canadian J Neurological Sciences 2002;29;404
Demo/practice website and database
Enter demo/practice ENOS trial web-site
Please note that data entered into the demo/practice website and database is not entered into the main/full trial database and does not contribute to trial data. However, this website and database replicates and demonstrates the functions of the main trial website and database.
Study personnel
Trial Steering Committee:
Independent Chairman - Graham Venables (Sheffield); Independent experts - Pierre Amarenco (Paris), Keith Muir (Glasgow); Members - Philip Bath (Nottingham), Kennedy Lees (Glasgow), Stuart Pocock (London), Joanna Wardlaw (Edinburgh), David Whynes (Nottingham); EME/MRC representative - Jane Sinclair (Southampton); University of Nottingham/sponsor representative - Angela Shone
International Advisory Committee:
Chair - Philip Bath, Australia - TBA, Canada - Stephen Phillips, China - Yong-Jun Wang, Egypt - Anwar El Etribi, Eire - Ronan Collins, Georgia - Maia Beridze, Greece - Yiannis Ellul, Hong Kong - Lawrence Wong, India - Kameshwar Prasad, Italy - Valeria Caso, Malaysia - Abdul Raman Ghani, New Zealand - John Gommans, Poland - Anna Czlonkowska, Romania - Szabolcs Szatmari, Saudi Arabia - Mohammed Al Jumah, Singapore - Hui Meng Chang, Spain - Exuperio de Tejedor, Sri Lanka - Asita de Silva, UK - Kennedy Lees
Trial Management Committee (Nottingham):
Chief Investigator - Philip Bath, Trial Manager - Sally Utton, Medic - Sandeep Ankolekar, UK Coordinator - Tanya Payne, Outcome & International Coordinator - Sharon Ellender, Statistician - Cheryl Hogg, Data/imaging Coordinator - Tanya Jones, Programming - Graham Watson, Liz Walker, Finance - Wim Clarke, Secretary - Yvonne Smallwood
Independent Data Monitoring Committee:
Chairman - Peter Sandercock (UK); Members - Kjell Asplund (Sweden), Colin Baigent (UK); Statistician - Veronica Moroz (UK)
Independent Events Adjudicator:
Daniel Bereczki (Hungary), Niki Sprigg (UK)
CT Scan Adjudicators:
Joanna Wardlaw, Rob Dineen, Jenny Becker, Panos Koumellis (UK)
Programming/database management:
Graham Watson, Liz Walker (UK)
Contact details
ENOS Trial Office
Division of Stroke
University of Nottingham
Clinical Sciences Building
City Hospital campus
Hucknall Road
Nottingham NG5 1PB
UK
Telephone: +44 (0)115 823 1770
Fax: +44 (0)115 823 1771
E-mail:enos@nottingham.ac.uk
Written by Philip Bath, last updated 22 July 2010
