Study into the reversal of septic shock with landiolol (beta blockade): STRESS-L Study protocol for a randomised trial

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Authors

  • Ranjit Lall
  • Dipesh Mistry
  • Emma Skilton
  • Nafisa Boota
  • Scott Regan
  • Anthony C Gordon
  • Daniel Francis McAuley
  • Gavin Perkins
  • Mervyn Singer
  • Duncan Young
  • Tony Whitehouse

External organisations

  • University of Warwick
  • Imperial College London
  • Queen's University, Belfast
  • University of Oxford
  • University Hospital Birmingham
  • University of Leicester
  • University College London Hospitals NHS Foundation Trust

Abstract

INTRODUCTION: In 2013, a single-centre study reported the safe use of esmolol in patients with septic shock and tachycardia who required vasopressor therapy for more than 24 hours. Although not powered to detect a change in mortality, marked improvements were seen in survival (adjusted HR, 0.39; 95%  CI, 0.26 to 0.59; p<0.001). Beta blockers are one of the most studied groups of drugs but their effect in septic shock is poorly understood; proposed mechanisms include not only the modulation of cardiac function but also immunomodulation.

METHODS AND ANALYSIS: STRESS-L is a randomised, open-label, non-blinded clinical trial which is enrolling a total of 340 patients with septic shock as defined by Sepsis-3 consensus definition and a tachycardia (heart rate ≥95 beats per minute (bpm)) after vasopressor treatment of at least 24 hours. Standard randomisation (1:1 ratio) allocates patients to receive usual care (according to international standards) versus usual care and a continuous landiolol infusion to reduce the heart rate between 80 and 94 bpm. The primary endpoint is the mean Sequential Organ Failure Assessment score over 14 days from entry into the trial and while in intensive care unit. Results will inform current clinical practice guidelines.

ETHICS AND DISSEMINATION: This trial has clinical trial authorisation from the UK competent authority, the Medicines and Healthcare products Regulatory Agency, and has been approved by the East of England-Essex Research Ethics Committee (reference: 17/EE/0368).The results of the trial will be reported first to trial collaborators. The main report will be drafted by the trial coordinating team, and the final version will be agreed by the Trial Steering Committee before submission for publication, on behalf of the collaboration.

REGISTRATION: The trial is funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) (Project Number: EME-14/150/85) and registered ISRCTN12600919 and EudraCT: 2017-001785-14.

Bibliographic note

Funding Information: Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme and managed by the NIHR (Project Number: 14/150/85). ACG is funded by an NIHR Clinician Scientist Fellowship. MS and GP are supported by NIHR senior investigators. Disclaimer The views expressed in this publication are those of the author(s) and not necessarily those of the EME, NHS, NIHR or the Department of Health. Competing interests TW reports grants from NIHR Efficacy and Mechanism Evaluation for the funding of STRESS-L (Project Number: EME-14/150/85) and during the conduct of the study; personal fees and non-financial support from AOP Orphan, manufacturer of Landiolol, outside the submitted work. MS has received travel expenses from AOP Orphan for delivering lectures. MS reports grants and other from NewB, grants from DSTL, other from Amormed, other from Biotest, other from GE, other from Baxter, grants from Critical Pressure, grants from Apollo Therapeutics, other from Roche, other from Bayer, other from Shionogi, outside the submitted work. ACG reports receiving grants from the NIHR and the NIHR Research Professorship; non-financial support from the NIHR Clinical Research Network and the NIHR Imperial Biomedical Research Centre during the conduct of the study; and personal fees from GlaxoSmithKline and Bristol-Myers Squibb outside the submitted work. DFM reports a grant from the NIHR EME programme for this study. Outside the submitted work, DFM reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim, Bayer, Novartis and Eli Lilly. In addition, his institution has received funds from grants from the NIHR, Wellcome Trust, Innovate-UK and others. In addition, DFM has a patent issued to his institution for a treatment for ARDS. DFM is a director of the Research for the Intensive Care Society and NIHR EME programme director. GP reports grants from National Institute for Health Research, during the conduct of the study; and he is a director of the Research for the Intensive Care Society. All other authors declare they have no competing interests. Publisher Copyright: © The Author(s), 2021.

Details

Original languageEnglish
Article numbere043194
Number of pages10
JournalBMJ open
Volume11
Issue number2
Publication statusPublished - 16 Feb 2021

Keywords

  • adult intensive & critical care, clinical trials, microbiology, statistics & research methods

ASJC Scopus subject areas