Landiolol and Organ Failure in Patients With Septic Shock
Author:
Whitehouse Tony12, Hossain Anower3, Perkins Gavin D.13, Gordon Anthony C.4, Bion Julian15, Young Duncan6, McAuley Danny78, Singer Mervyn9, Lord Janet2, Gates Simon10, Veenith Tonny12, MacCallum Niall S.11, Yeung Joyce13, Innes Richard12, Welters Ingeborg13, Boota Nafisa3, Skilton Emma3, Ghuman Belinder3, Hill Maddy3, Regan Scott E.3, Mistry Dipesh3, Lall Ranjit3, Veenith Tonny14, Patel Jaimin14, Murphy Nick14, Bangash Mansoor14, Torlinski Tomasz14, Talbot Nicholas14, Snelson Catherine14, Parekh Dhruv14, Desai Amisha14, Kotada Mary14, May Chin Yin14, Holden Sophie14, Neal Aoife14, Ventura Maximina14, Pope Martin14, Harkett Samantha14, McGhee Christopher14, Fellows Emma14, Bamford Amy14, Carrera Ronald14, Ellis Karen14, Spruce Elaine14, Despy Liesl14, Porter Stephanie14, Bergin Colin14, Gouny Stephanie14, Smith Hazel14, Mason Tracy14, Dooley Natalie14, Clark Amy14, Yeung Joyce14, Gresty Jo14, Melody Teresa14, Reeves Ellie14, Smith Rachel14, Sampson Julia14, Team BHH Critical Care Unit ACCP14, Nutt Chris14, Mcnamee James14, Mcauley Danny14, Boyle Anen14, McGinley Loren14, Wright Chris14, Ward Kathryn14, Macartney Lauren14, Mccann Justine14, Wells Brian14, Mills Janette14, Bannon Leona14, O’Neill Aisling14, Finn Stephanie14, Gordon Anthony14, Antcliffe David14, Brett Stephen14, Banach Dorota14, Cabreros Leilani14, Curran Laura14, Sousa Arias Sonia14, Rojo Roceld14, Fernandez de Pinedo Artaraz Ziortza14, Coghlan Phoebe14, Templeton Maie14, ElHaddad Ahmed14, Sabine Loko Zohonon14, Barker Gareth14, MacCallum Niall14, Brealey David14, Singer Mervyn14, Warnes Kristian14, Bason Nina14, Filipowicz Dorota14, Bercades Georgia14, Hass Ingrid14, Ryu Jung14, Smyth Deborah14, Ilano Dorothy14, Harvey Dan14, Conner Louise14, Ryan Lucy14, Peters Cecilia14, Meredith Megan14, Mcaulay Megan14, Whitman Zoe14, Morris Lucy14, Woodford Claudia14, Hodgkinson Sally14, Finucane Sonya14, Camporota Luigi14, Shankar-Hari Manu14, Ostermann Marlies14, Bociek Aneta14, Lim Rosario14, GrauNovellas Neus14, Palmer Natalie14, Cape Angela14, Kelly Anea14, Arbane Gill14, Campos Sarah14, Singh Michael14, Yoo Jinny14, Innes Richard14, Dempsey Fiona14, Doble Patricia14, Purnell Rebecca14, Tait Moira14, Hutter Jo14, Pawley Corinne14, Rowe Joy14, Wane Catherine14, Burgess Richard14, Thomas Ashly14, Paul Pulak14, White Brenda14, Lovegrove Wayne14, Gill Mandy14, Wade Lynne14, Brear Tracy14, Dhokia Vishal14, Jackson Debbie14, Shelton Sarah14, Kirk Jill14, Boulton Anew14, Roy Alistair14, Rostron Anthony14, Elcioglu Zeynep14, Woods Lindsey14, Cornell Sarah14, Betts Rebecca14, Holden Jill14, Laybourne Stephen14, Rogerson Kimberley14, Bewley Jeremy14, Johnson Rebekah14, Chillingworth Anna14, Gumbrill Bethany14, Galvin Hilary14, Wright Kim14, Efford Georgia14, Corcoran Kathleen14, Cole Libby14, Sweet Katie14, Webster Denise14, Grimmer Lisa14, Paris Gemma14, Searles Chloe14, Garland Zoe14, Gibson Charly14, Hutchings Melanie14, Walters Fiona14, Kelly Sinead14, Scaife Lorraine14, Littlewood Kelly14, Leavy James14, Todd Shirley14, Gordon Elizabeth14, Heddon Sadie14, Mariano Victor14, Gupwell Karin14, Appelboam Rebecca14, Keenan Samantha14, Brady Cassie14, Mew Ian14, Chambler Duncan14, Williams Sarah14, Ashcroft Pauline14, Williams Patricia14, Rees James14, Wiseman Sophie14, Horton Sarah14, Shortland Mark14, Dukes Stephanie14, Ball Andy14, Spivey Michael14, Stephens Jennie14, Bean Sarah14, Burt Karen14, Chapman Rachel14, Richards Carol14, Moore Lorraine14, Allsop Linda14, Wynn Amber14, Latty Louise14, Waddy Sam14, Spencer Kayleigh14, Stowe Bethan14, Cox Georgina14, McMillan Helen14, Lankester Liana14, Wells Colin14, Squire Rosalyn14, Marner Mike14, Jackson Robert14, Nikitas Nikitas14, Dickson Stuart14, Reschreiter Henrik14, Bromilow James14, Keegan James14, Loew Chris14, Power Ken14, Briggs Spike14, Camsooksai Julie14, Patch Sarah14, Jenkins Sarah14, Power Sharon14, Woodward Elizabeth14, Pogson David14, Daly Zoe14, Rose Steve14, Collins Aimi14, Phelps Amy14, Claridge Helen14, Minnis Christine14, Inglis Sarah14, Brimfield Lutece14, Wong Charlotte14, Welters Ingeborg14, Williams Karen14, Waugh Victoria14, Patrick-Heselton Julie14, Johnson Emily14, Shaw David14, Johnston Brian14, Crews Maryam14, Waite Alicia14, Sankar Vinoth14, Walker Jonathan14, Turton Peter14, Wenstone Richard14, Fernandez Roman Jaime14, Hall Alison14, Lopez Martinez Maria14, Oliver Hamilton David14, Coey David14, Shelley Philip14, Goulding Martin14, Kavanagh Karen14, Marron Ann14, Allsop Hannah14, Hopkins Phil14, Smith John14, Noble Harriet14, Pappa Evita14, Finney Clare14, Heyler Sinead14, Clarey Emma14, Cockrell Maeve14, Therese Depante Maria14, O'Reilly Kevin14, Waterhouse Christopher14, Chu Vicky14, Gordon Joanne14, Marchant Greg14, Chandler Stuart14, Haile Senait14, Flanagan Joanna14, Notcheva Gaynor14, Jimenez Dom14, Gill Dilbagh14, Jamadarkhana Sunil14, Gohil Sunita14, Dabbagh Sura14, Chick Katy-Jane14, Cruz Carina14, Anumakonda Vikram14, Moore Vanessa14, Stanton Lisa14, Westwood Sharon14, Smith Jacqueline14, Reid Karen14, Gidda Ranjit14, Anastasescu Elena14, Salem Karim14, Mooradun Mohamed14, Reay Michael14, Ekbal Nasirul14, McNeil Margaret14, Filipe Helder14, Nandani Aarti14, Pakou Glykeria14, de Neef Mark14, Mingo Sara14, Maharajh Amitaa14, Nandhabalan Prashanth14, Billyard Thomas14, Wild Laura14, Bremmer Pamela14, Ward Geraldine14, McGurk Fiona14, Deol Rajbinder14, Morgan Catherine14, Pachoo Kirandeep14, Phillips Barbara14, Boyd Owen14, Phillips Claire14, Hindocha Rakhee14, Age Stephen14, Porter John14, Harrison Alex14, Evans Lynn14, Ortiz-Ruiz de Gordoa Louise14, Wlazly Dominika14, Anews Tomas14, West Jess14, Attwood Ben14, Jefferson Paul14, Parsons Penny14, Mason Sophie14, Campbell Bridget14, Jones Julia14, Webb Kathryn14, Spicer Karen14, Day Angela14, Stagg Camilla14, Ayesha Shah Noor14, Purcell Ian14, Shafiq Lucy14, Carle Coralie14, Chilvers Rebecca14, MacColl Heather14, Pope Alan14, Holder Anew14, Butterworth-Cowin Nicola14, Davies Matthew14, Wilmer Louise14, Ismail Nadeem14, Gurung Sneha14, Murphy Piers14, Elkington Toby14, Camilleri Matthew14, Charnock Rob14, Shevlin Claire14, McGregor Emma14, Clarke Chris14, Hinds Judith14, Hughes Sophie14, McKee Raymond14, McFarland Denise14, McNulty Roisin14, Breen Andy14, Wilby Elizabeth14, Youngs Nora14, French Richard14, Colquhoun Suzie14, Posnett Claire14, Howcroft Clare14, Taylor Anew14, Whiteley Simon14, Ogg Bethan14, Long Kate14, Tomkinson Alicia14, Clement Ian14, Shrestha Tara14, Dunn Leigh14, Calder Verity14, Babio-Galan Maite14, Zwiggelaar Kimberley14, Mitchell Anne14, Stephenson Julie14, Rigden Lesley14, Davison Jude14, Carter Joseph14, Howard Kate14, Cahill Hazel14, Grainger Lia14, Cottrell-Howe Poppy14, Rowbotham Abigail14, Jeffery Laura14, Waterman Emily14, Fletcher Arran14, Guy Zoe14, Birkinshaw Isabel14, Ingham Jo14, Scott Zoe14, Stead Samantha14, West Raha14, Shanmugasundaram Pradeep14, Abrams Judith14, Hambrook Geraldine14, Manso Katarina14, Scott Sally14, Husain Iram14, Chan Evelyn14, Gettings Siobhan14, Hormis Anil14, Walker Rachel14, Collier Dawn14, Graham Cheryl14, Murray Victoria14, Curtis Katy14, Widdop Charlotte14, Kimpton Sarah14, Oakley Susan14, Afzal Zirlish14, Varley James14, Polgarova Petra14, Johnston Andrew14, Whitehead Lynne14, Conway Morris Andrew14, Mahroof Razeen14, Teixeira Sofia14, Ali Nazrudeen14, Wilkinson Jonny14, Lyon Alex14, Mills Charlotte14, Hall Kathryn14, Grantham Gayna14, Campey Lorraine14, Cronshaw Helen14, Malanjum Livia14, Dudgeon Lucy14, Hinchley Clare14, Langhon Stephen14, Hosea Jane14, Hillyer Anea14, Kontogonis Rachel14, Ndefo Oninye14, Robinson Laura14, Kaye Callum14, Sim Kevin14, Scott Ian14, Scott Teresa14, Anderson Felicity14, Mitchell Wendy14, Cooper Patricia14, MacBrayne James14, Willox Fiona14, Richmond Kate14, Colleron Rebecca14, Trumper Erin14, Was Bartosz14, Christie Michael14, Johnson Amber14, Price Gillian14, Sim Malcolm14, Docking Robert14, McQueen Scott14, Kennedy-Kay Sophie14, Abel Lynn14, Henderson Steven14, McLeash Kirsty14, Gratrix Anew14, Martinson Victoria14, Foster Louise14, Stones Elizabeth14, Lowthorpe Vicki14, Crawley Daniel14, Leaver Susannah14, Farnell Ward Sarah14, Pepermans Saluzzio Romina14, Robinson Frances14, Delgado Carlos14, Gray Geraldine14, Kanu Rebecca14, Oakley Robert14, Keates Karen M.14, Walsh Tim14,
Affiliation:
1. University Hospitals of Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom 2. Institute of Inflammation and Ageing, University of Birmingham, United Kingdom 3. Warwick Clinical Trials Unit, University of Warwick, Coventry, United Kingdom 4. Division of Anaesthetics, Pain Medicine & Intensive Care, Faculty of Medicine, Imperial College London, London, United Kingdom 5. Institute of Clinical Sciences, University of Birmingham, United Kingdom 6. Kadoorie Centre for Critical Care Research, Nuffield Division of Anaesthesia, University of Oxford, Oxford, United Kingdom 7. Regional Intensive Care Unit, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, United Kingdom 8. The Wellcome Wolfson Institute for Experimental Medicine, Queens University Belfast, Belfast, United Kingdom 9. Centre for Intensive Care Medicine, Department of Medicine and Wolfson Institute for Biomedical Research, University College, London, United Kingdom 10. Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom 11. University College London Hospitals NHS Foundation Trust, Gower Street, London, United Kingdom 12. Musgrove Park Hospital, Taunton and Somerset NHS Foundation Trust, Taunton, United Kingdom 13. Royal Liverpool University Hospital, Liverpool, United Kingdom 14. for the STRESS-L Collaborators
Abstract
ImportancePatients with septic shock undergo adrenergic stress, which affects cardiac, immune, inflammatory, and metabolic pathways. β-Blockade may attenuate the adverse effects of catecholamine exposure and has been associated with reduced mortality.ObjectivesTo assess the efficacy and safety of landiolol in patients with tachycardia and established septic shock requiring prolonged (>24 hours) vasopressor support.Design, Setting, and ParticipantsAn open-label, multicenter, randomized trial involving 126 adults (≥18 years) with tachycardia (heart rate ≥95/min) and established septic shock treated for at least 24 hours with continuous norepinephrine (≥0.1 μg/kg/min) in 40 UK National Health Service intensive care units. The trial ran from April 2018 to December 2021, with early termination in December 2021 due to a signal of possible harm.InterventionSixty-three patients were randomized to receive standard care and 63 to receive landiolol infusion.Main Outcomes and MeasuresThe primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score from randomization through 14 days. Secondary outcomes included mortality at days 28 and 90 and the number of adverse events in each group.ResultsThe trial was stopped prematurely on the advice of the independent data monitoring committee because it was unlikely to demonstrate benefit and because of possible harm. Of a planned 340 participants, 126 (37%) were enrolled (mean age, 55.6 years [95% CI, 52.7 to 58.5 years]; 58.7% male). The mean (SD) SOFA score in the landiolol group was 8.8 (3.9) compared with 8.1 (3.2) in the standard care group (mean difference [MD], 0.75 [95% CI, −0.49 to 2.0]; P = .24). Mortality at day 28 after randomization in the landiolol group was 37.1% (23 of 62) and 25.4% (16 of 63) in the standard care group (absolute difference, 11.7% [95% CI, −4.4% to 27.8%]; P = .16). Mortality at day 90 after randomization was 43.5% (27 of 62) in the landiolol group and 28.6% (18 of 63) in the standard care group (absolute difference, 15% [95% CI, −1.7% to 31.6%]; P = .08). There were no differences in the number of patients having at least one adverse event.Conclusion and RelevanceAmong patients with septic shock with tachycardia and treated with norepinephrine for more than 24 hours, an infusion of landiolol did not reduce organ failure measured by the SOFA score over 14 days from randomization. These results do not support the use of landiolol for managing tachycardia among patients treated with norepinephrine for established septic shock.Trial RegistrationEU Clinical Trials Register Eudra CT: 2017-001785-14; isrctn.org Identifier: ISRCTN12600919
Publisher
American Medical Association (AMA)
Cited by
4 articles.
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