The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: Study protocol for a randomised controlled trial (2018)

Type of publication:
Journal article

Author(s):
Al-Shahi Salman R.; Dennis M.S.; Innes K.; Drever J.; Dinsmore L.; Williams C.; Whiteley W.N.; Sandercock P.A.G.;  Sudlow C.L.M.; Murray G.D.; White P.M.; Newby D.E.; Sprigg N.; Werring D.J.; Dennis M.; Sudlow C.; Whiteley W.; Lerpiniere C.; McCormick K.; Perry J.; Parakramawansha R.; Hunter N.; Doubal F.; Paulton R.; O’Brien R.; Burgess S.; Mead G.; Taylor P.; MacLeod M.-J.; Maclennan B.; Clarke R.; Taylor V.; Klaasen K.; Crouch N.; Jagpal B.; Furnace J.; Irvine J.; Gow H.; Joyson A.; Nelson S.; Ross S.; Davies R.; Jose D.; Robinson N.; Codd L.; Dodd A.; Moroney H.; Weir P.; Little V.; Gott V.; Sangster G.; Owings P.; Cherian S.; Downham S.; Epstein D.; Webber A.; Qureshi S.; Nicholas P.; Krishnamurthy V.; Shukla A.; Jones I.; Ahmed A.; Cunningham M.; Zahoor T.; Johnson S.; Denniss C.; Albazzaz M.; Ramadan H.; Maguire S.; Patterson C.; Bellfield R.; Hairsine B.; Quinn O.; Hooley M.; Nair A.; Alam M.I.; Greig J.; Rana P.; Robinson M.; Sajid M.; Ball M.; Gascoyne R.; Ghaly G.; Raghunathan S.; Clarke J.; Wilkes G.; Law Z.; Appleton J.; Matias O.; Jackson B.; Keshvara R.; Whittamore K.; Jordan C.; Sheikh S.; Roffe J.; Gilzeane N.; Krishnan K.; Buck A.; Havard D.; Hedstrom A.; Shelton F.; Godfrey M.; Webster T.; Haider S.; Seagrave S.; Leason S.; Nallasivan A.; Chatterjee K.; Perkins C.; Mohd Nor A.; Persad N.; Eglinton C.; Brown C.; Weinling M.; Shah A.; Baker J.; Hyams B.; Kini M.; Fong R.; Chadha D.; Walstow D.; Proeschel H.; Sharpe S.; Horton S.; Jones S.; Byrne A.; McGhee C.; Smart A.; Copeland C.; Dutta D.; Bakawala R.; O’Connell S.; Hughes C.; Brown P.; Davis F.; Collins K.; Ward D.; Turfrey J.; Rudd T.; Marks K.; Kullane S.; Jonathan B.; Bhalla A.; Yip B.; Bell M.; MacInnes B.; Macliver L.; Esson D.; Yadava R.; Stafford S.; Reddan J.; Sangombe M.; Azhar K.; Jenkins C.; Price F.; Mercer L.; Vasileiadis E.; Mason C.; Aweid B.; Holden M.; Parry A.; Landers G.; Broughton D.; Chapman K.; Sigsworth A.; Tryambake D.; Young A.; Dixon L.; Bergin A.; Barber M.; Brodie F.; Anjum T.; Connor L.; Tucker S.; Thomas S.; Davies C.; Slade P.; Treadwell S.; Wani M.; Beaty T.; Krishnan M.; Dacey L.; Spencer J.; Quinn L.; Chenna S.; Storton S.; Jones T.; Jones H.T.; Hussain M.; Homan J.; Foster E.; Brotherton L.; Durman H.; Hunt N.; Foot J.; Whitcher A.; Pawley C.; Khan M.; Whiting R.; Harvey M.; Brown S.; Foote L.; Richard B.; Triscott C.; Edwards M.; Lawson H.; Wallace R.; Nott C.; Moseley S.; Buckle S.; Sarah P.; Whiteman J.; Fotherby K.; Butler D.; Willberry A.; Ahmad N.; Jennings-Preece K.; Baig F.; Morgan D.; Stevens A.; Metcalf K.; McDonald S.; Ravenhill G.; Anversha A.; Shinh N.; Perfitt R.; Greenwood R.; Saada J.; Waterfield K.; Sutton P.; Jagger J.; Wiltshire A.; Luder R.; Johnson V.V.; Bridger H.; Bhargava M.; Gallagher J.; Adesina T.; van Someren C.; Carpenter M.; Walker M.; Stanners A.; Ball J.; Jackson L.; Datta P.; Bateman G.; Fathima R.; Davey R.; Needle A.; Siddegowda P.; Ponnambath S.; Suttling A.; Harrington-Davies Y.; Butler R.; James M.C.; Valentine M.S.; Dobson T.; Howard P.; Tandy J.; Hyatt L.; Jarrett D.; Saulat A.; Sims D.; Willmot M.; Green C.; Jones R.; Cunningham J.; Maiden S.; Sutton C.; Hurley J.; Littleton E.; Shekhar R.; Crown R.; Ahmed I.; Fuller S.T.; Gilham E.; Andole S.; Gadapa N.; Dunne M.K.; Krommyda M.; Burssens E.; King S.; Goorah N.; Bell A.; Patel F.; Tomlinson B.; Duberley S.; Singh A.; Kelly C.; Walford J.; Harrington F.; Schofield C.; Lucas L.; Ellis S.; Bond K.; Mate A.; Adie K.; James A.; Maund B.; Courtauld G.; Mudd P.; Hemsley A.; Thorpe K.; Gupwell K.; Goff A.; Sword J.; Roughan C.; Strain D.; Cageao J.; Bowring A.; Keenan S.; James M.; Kingwell H.; Miller K.; Harkness K.; Doyle C.; Majis A.; Stocks K.; Maatouk A.; Barron L.; Dakin K.; Lindert R.; Kamara C.; Bayliss P.; Redgrave J.; Kibutu F.; Blank C.; Ali A.; Balitska O.; Birchall K.; Richards E.; Howe J.; Smyth N.; Giallombardo E.; Sykes L.; Wilson J.; Langhorne P.; McAlpine C.; Humphreys L.; Iqbal M.S.; Graham R.; Kerr G.; Wright F.; Kumar P.; Thomas P.; Culmsee C.; Huggett I.; Dunn M.L.; Barker J.; Manoj A.; Fitzsimmons P.; Lopez M.P.; Sharma N.; Cox P.; Fletcher G.; Wilkinson M.; Emsley H.; Raj S.; Doyle D.; Gregory B.; Punekar S.; Sultan S.; McLoughlin A.; Pasco K.; Balazikova M.O.; Nasim A.; Peixoto C.; Kane I.; Pitt- Ford A.; Hervey S.; Thompson P.; Latter M.L.; Barbon E.; Breeds J.; Rajkumar C.; Gainsborough N.; Gaylard J.; Choulerton J.; Shaw L.; Madigan B.; Howcroft D.; Lucas S.; Stone A.; Avis J.; Gbadamoshi L.; Button D.; Stephanie M.; Dow L.; Davis M.; Thompson T.; Hogg V.; Hays C.; Fawcett M.; Atkinson N.; Guy H.; Woodward S.; Parry-Jones A.; Marshall S.; Jarapa R.; Lee S.; Harrison L.; Johnes M.; Oloughlin V.; Wood E.; Perez J.; Naing Z.; Morell J.; Marsden T.; Ingham A.; Burger I.; Shaw K.M.; Hall A.; Punter M.; Weir N.; Evans S.; Walters A.; Gartrell M.I.; Smith M.F.; Cox M.C.; Smith C.N.S.; Egerton S.; Creeden R.; Marigold J.R.; Blades A.; Crawford P.; Battersby- Wood E.; Pressly V.; Allen C.; Howard G.; Muir K.; Kalladka D.; Smith W.; Day N.; Moreton F.; Cheripelli B.K.; Huang X.; Welch A.; El Tawil S.; Ramachandran S.; Crosbie C.; Elliot J.; Cluckie G.; Clarke B.; Dayal N.; Orefo C.; Adedoyin T.; Ghatala R.; Clarke N.; Jones V.; Blight A.; Lovelock C.; Chopra N.; Moynihan B.; Kennedy K.; Williams R.; Kerin M.L.; Jeyaraj M.N.; Choy L.; Watson F.; Trippier S.; O’Reill J.; Haque M.; Symonds S.; Maanoosi M.; Herman J.; Vassallo J.; Krishnamoorthy S.; Cochrane H.; Walter D.; O’Connell J.; Fox C.; Krishnamurthy R.; Osborne E.; Smith A.; Mokoena B.; Gulliver D.; Brew H.; Myint M.; Majmudar N.; Bunea G.; Sattar N.; *Srinivasan M.; *Mukherjee I.; *Motherwell N.; *Donaldson D.; *Campbell R.; *Hurford F.; Thavanesan K.; David O.; Tiwari D.; Hann G.; Longland B.; Bell J.; Rogers M.E.; Bagnall M.C.; Iqbal M.A.; Keltos M.; Jupp B.; Roberts J.; Cox C.; Ovington C.; Bhaskaran B.; Garfield-Smith J.; Buxton J.; Horan K.; Ayres G.; Bearne H.; Tomlin D.; Szabo S.; Kelly D.; Salih I.; Bhakri H.; Fitzell P.; Wilson D.; Wroath B.; Dynan K.; Power M.; Thompson S.; Ghosh S.; Henry M.; Gilmour D.; Barrie E.; Kenton A.; Nyabadza M.S.; Martin M.I.; Hunt B.; Hassan H.; Dallol B.; Muddegowda G.; Hiden M.J.; Maguire H.; Grocott J.; Finney K.; Barry A.; Roffe C.; Lyjko S.; Sanyal R.; Remegoso A.; Ferdinand P.; Butler A.; Abano N.; Causley M.C.; Denic H.; Carpio R.; Stevens S.; Moores A.; Varquez R.; Pai Y.; Bruce D.; Dima S.; Baliga V.; Naeem M.; Rogers G.; Brown E.; Hayman R.; Garside M.; Dhakal M.; Smith G.M.; Clayton S.; Orugun E.; Poultney U.; Glover R.; Crowther H.; Thornthwaite S.; Webb T.; Beranova E.; Walker S.; Cosier T.; Rudenko H.; Cowie L.; Verrion A.; Thomson A.; Gamble E.; Charles B.; Grue R.; Blane S.; Hague A.; Rashed K.; Vickers C.; Wood D.; Board J.; Buckley C.; Allison J.; Board S.; William-Yesson B.; Balian L.; Keeling E.; Kar A.; Halse O.; Nguyen V.; Harvey K.; Gardener L.; Mashate S.; Tilley V.; Wilding P.; Geraghty O.; Hazel B.; Harrison T.; Cuenoud L.; Auld G.; Erumere E.; Redjep O.; Grimwood G.; Howaniec L.; Hove D.; Salek-Haddadi A.; Saastamoinen K.; Argandona L.; Wiggam I.; Wallace A.; Cuddy S.; Tauro S.; Hunter A.; Kerr E.; Fulton A.; Putterill J.; Kakar P.; Jha R.; Gallifent R.; Pusalkar A.; Chan K.; Dangri P.; Crabtree K.; Beadle H.; Cook A.; Black T.; Cronin J.; Fennelly R.; Tribbeck M.; Clarke C.; Miriam S.; Anthony A.; Mead D.; Esisi B.; Bokhari M.; Cassidy T.; McClelland B.; Cooper M.; Wynter I.; Rajapakse A.; Nasar M.; Anwar I.; Ramshaw A.; Annamalai A.; Crawford S.; Nozedar T.; Skinner H.; Kumar B.; McArdle D.; Holmes C.; Dodd E.; Clarke S.; Caine S.; Baker P.; Murphy P.; Osborn M.; Guthrie L.B.; Steele A.; Devitt N.; Mangion D.; Fletcher J.; Hardwick A.; Constantin C.; Markova S.; Lawrence T.; Subramonian S.; Temple M.N.; Owusu-Agyei P.; Butterworth-Cowin N.; Werring D.; Hogan C.; brezitski M.; Elliott E.; Francia N.; Ashton A.; Hostettler I.; Oji N.; Banaras A.; Patel K.; Crook L.; Watchurst C.; Erande R.; Sekaran L.; Mohammed N.; Chauhan M.; Sethuraman S.; Simon R.; Bharaj K.; Tate M.; Justin F.; Phiri D.; Hewitt J.; Gray J.; Mardania R.; Procter M.S.; Elfandi K.; Khan U.; Ragab S.; Knops K.; Jinks E.; Dickson C.; Gleave L.; Leggett J.; Dube J.; Garcia T.; McIlmoyle J.; Anwar S.; Dhar S.; Jones K.; Jeffs C.; Dickinson C.; Howard J.; England T.; Donnelly R.; Maddula M.; Hassan A.; Veraque E.; Kambafwile M.; Makawa L.; Randall M.; Papavasileiou V.; Waugh D.; Ispoglou S.; Hayes A.; Ankolekar S.; Evans R.; Ni H.; Graham C.; Jose J.; Milligan J.; Rahman B.; Findlay P.; Macaden A.; Shread I.; Keegan B.; Blair C.; Kelly J.; Doherty M.; Dewar R.; White J.; Thomas K.; Cohen D.; David A.; Owoyele E.; Njoku K.; Poku P.; Sukdeo V.; Chandrakumar A.; Chamberlain A.; Abbdulsaheb M.; Guo F.; Oshodi M.A.; Licenik R.; Devine J.; Davies S.; Nisar N.; Niranchanan R.; Roganova T.; Mpelembue M.; Burgess L.; Bathula R.; Ngwako M.; Eveson D.; Mistri A.; Stephens C.; Musarrat K.; Lam M.Y.; Sattar S.; Khan S.; Moqsith M.; Manning L.; Patel C.; Schulz U.; Kennedy J.; Ford G.; Harston G.; Teal R.; Mathieson P.; Lenti G.; Reckless I.; Cullen C.; Stevenson S.; Harrison M.; Ewing J.; Shackcloth D.; Durairaj R.; Zoe M.; Ingram T.; Thant H.; Peters J.; Sutton V.; Ivatts S.; Amey I.; Clayton-Evans L.; Baird Y.; Sally M.; Newton S.; Guyler P.; Ng K.X.; Prabakaran R.O.; Ngo D.; Rashmi S.; Coward L.; Menon N.; Kelavkar S.; Kunhunny S.; Sinha D.; Siddiqui A.; Loganathan T.; Tysoe S.; Shah S.; Kalathil L.; Gautam N.; Meir J.; Bailey D.; Salehin M.; Miller R.; Kelly A.; Rayessa R.; Rodgers A.; Wilson L.; Naylor C.; Wilson S.; Clarkson E.; McCarron M.; McVerry F.; McKee S.J.; Cvoro V.; Ullah K.; Chapman N.; Couser M.; Mcauley S.; Pound S.; Nicolson A.; Imam J.; Wood L.; O’Brien E.; Hannon N.; Finlay S.; Hayhoe H.; Handley D.; Kelly S.; Mcgee J.; Mitchell J.; Amis E.; Sesay J.; Crisp S.; Francis J.

Citation:
Trials; Mar 2018; vol. 19 (no. 1)

Abstract:
Background: For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. Methods/design: The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigatorled, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Discussion: Final results of RESTART will be analysed and disseminated in 2019.

Link to full-text [no password required]

Normal acutely performed CT scan of the brain may give a false sense of safety prior to use of antiplatelets in transient focal (2017)

Type of publication:
Conference abstract

Author(s):
*McNeela N.; *Srinivasan M.

Citation:
Cerebrovascular Diseases; Jul 2017; vol. 43 ; p. 116

Abstract:
Transient focal neurological episodes (TFNE) are frequently assumed to be transient ischaemic attacks (TIAs) in older patients who are then started on antiplatelets for stroke prevention. Imaging with a CT scan of the brain reported as normal or not suggesting haemorrhage can give a false sense of security with regard to therapeutic decision making. Current UK stroke guidelines do not emphasise the need for imaging (either CT or MRI) in transient ischaemic attacks with NICE guidance recommending treat with aspirin immediately and then refer to stroke services for further management. Imaging is then only recommended for patients where the vascular territory or pathology is uncertain with diffusion weighted MRI scans. In cases where MRI is contraindicated second line imaging is a CT head. We present two cases of patients who presented with symptoms of TFNEs treated as TIAs who then subsequently developed haemorrhagic strokes. The first case is of an 80 year old lady with new onset atrial fibrillation who presented with transient face and arm paraesthesia and dysarthria. Following a normal CT head she was started on anticoagulation and discharged home. She subsequently represented with a further two episodes and each time underwent a repeat imaging which again showed no abnormalities until she eventually succumbed to a massive right cortical intracranial haemorrhage. The second case involves a 68 year old gentleman with no significant past medical history other than a recent headache who presented with recurrent symptoms of left face and arm paraesthesia and dysarthria. A CT scan of the brain was normal and so he was treated with antiplatelets for a presumed TIA and discharged. However within six hours he deteriorated with dense left hemiplegia and reduced consciousness. A repeat CT showed a large right frontoparietal bleed with midline shift requiring referral to neurosurgeons. These cases highlight how a CT head in an acute presentation with transient symptoms can be misleading. One option would be consideration of blood sensing MRI scans in investigation of TFNE verses TIA diagnoses. As TFNEs often to present as descending paresthesia, we would recommend all patients with this presentation to undergo urgent inpatient MRI scans before being commenced on treatment.

Obstacles to consent for intravenous rtPAin acute stroke (clinical audit and survey) (2016)

Type of publication:
Conference abstract

Author(s):
*Alamgir M., *Srinivasan M., *Ghani U.

Citation:
Cerebrovascular Diseases, May 2016, Vol. 41, Supplement 1, p.285-286

Abstract:
Introduction: Intravenous thrombolysis with rTPA is the standard of care for the treatment of acute ischaemic stroke within 3 hrs (up to 4.5 in suitable Pt) after stroke onset. Even with clear evidence of benefit there is increased risk of harm . Due to complex risk & benefit aspects of the treatment the current guidance recommends consent should be obtained for intravenous thrombolysis whenever possible. Our objective was to review the current practice in documentation of consent and also identify the factors which contribute in fauilu-re to obtain consnet Method: We have randomly selected 25 Patient’s notes those were admitted from November 2014 to May 2015 and looked for the completed consent form or documentation elsewhere. We have also conducted a survey among Stroke Consultants and medical registrars (who are involved in administration of intravenous thrombolysis) to identify the reasons responsible for failure to obtain consent in acute setting. Results: The documentation of consent was noted to be very poor (either on consent form or documentation elsewhere in notes). Consent form was completed only in 27% cases and there was no clear documentation of reasons for not obtaining consent in the rest. Survey results showed that the only 40% were aware of the consent form in pathway. Reasons of not obtaining consent were , Time pressure = 40%, Patient factors = 40, Ignorance of statistics( Not sure about actual statistics) = 20 %. Conclusion: We have recommended that the use of a consent form with visual illustrations of statistics of risks & benefits to make consent process easier to understand for patients & save time in acute settings. Alternatively suggested that If patient does not have capacity for consent then there should be every effort made to involve the family and next of kin in decision making process (Figure Presented).

Link to more details or full-text: http://misc.karger.com/products/CED_2016_041_S1/index.html

Thrombolysis for stroke in pregnancy at 39 weeks gestation with a subsequent normal delivery (2015)

Type of publication:
Journal article

Author(s):
*Ritchie J., *Lokman M., *Panikkar J.

Citation:
BMJ Case Reports, August 2015, vol./is. 2015

Abstract:
Stroke during pregnancy is fortunately a rare event, however, it can have severe consequences, with 9.5% of all maternal deaths being related to stroke. The most common presentation is an ischaemic stroke. There has been much debate as to the correct treatment for such cases’ and whether thrombolysis can be used safely in pregnancy. Our case describes a 28-year-old woman with a previous normal vaginal delivery presenting in her third trimester with a sudden onset of dense left hemiparesis. She was successfully treated with alteplase, an intravenous recombinant tissue-type plasminogen activator, and made a full recovery after normal delivery of a healthy infant. This case report highlights one of the first documented successful outcomes from thrombolysis for this condition in the UK and may help inform future management of these women.

Link to full-text: http://casereports.bmj.com/content/2015/bcr-2015-209563.full.pdf

The first case of thrombolysis for stroke in pregnancy in the UK (2014)

Type of publication:
Conference abstract

Author(s):
*Ritchie J., *Lokman M., *Panikkar J.

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology, November 2014, vol./is. 121/(7), 1470-0328 (November 2014)

Abstract:
Case: A healthy 28-year-old Caucasian woman presented to the Royal Shrewsbury Hospital (RSH) in her second pregnancy at 39 weeks of gestation with a sudden onset of dense left hemiparesis. This woman had no preceding risk factors. An urgent CT scan showed no acute changes suggesting a diagnosis of ischaemic stroke. Through discussion between the stroke specialist and consultant obstetrician, it was decided for thrombolysis which was performed in the emergency department prior to transfer to a larger hospital with stroke facilities. We wished to discover how many other women had undergone thrombolysis for stoke in pregnancy and the associated risks. We conducted a literature review concentrating on stroke and pregnancy including known risk factors and thrombolyis in pregnancy. We have found no other documented case of thromboylsis being used for stroke in pregnancy in the UK. Additionally there are many case reports not from the UK that demonstrate good maternal and fetal outcomes after thromobolysis. Conclusion: Our case appears to be the first reported case of thrombolysis for stroke in pregnancy in the UK. All post investigations have so far come back as normal, which is unusual as most other cases have had known risk factors for stroke. Our patient has recovered well post thrombolysis, which demonstrates the importance of dealing with stroke in pregnancy efficiently to allow thrombolysis to be achieved quickly. Although the risks and benefits need to be weighed up on an individual basis, our case and the relevant literature show that thrombolyiss can be safely used in pregnancy with good maternal and fetal outcomes.

Link to more details or full-text: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00134415-201411006-00021&LSLINK=80&D=ovft