BALTI 2: The Beta-2 Agonist Lung Injury Trial 2
Lead Research Organisation:
University of Warwick
Department Name: Research Support Services
Abstract
Acute Respiratory Distress Syndrome (ARDS) is a common and extremely serious type of respiratory failure among patients in intensive care units. Nearly half of the patients who suffer ARDS die, and many of the survivors have long-term health problems. A small-scale study suggested that intravenous salbutamol given for 7 days early in the course of ARDS may help more patients to survive. This project will determine whether this is correct, by comparing the results among over 1300 patients, half of whom (decided at random) will receive salbutamol and half of whom will receive an inactive solution.
Technical Summary
BALTI 2 is a multicentre, randomised, double-blind, placebo-controlled trial to determine whether intravenous salbutamol infusion in critically ill adult patients with acute respiratory distress syndrome (ARDS) influences 28 day mortality. The setting will be adult Intensive Care Units (ICUs) within the National Health Service in the UK with the ability to provide full (Level 3) Intensive Care.
The BALTI 2 trial is an effectiveness study, where the allocation of salbutamol or placebo infusion is determined randomly, but all other treatment decisions are left to the clinicians managing the patient. 1344 patients will be randomised within 72 hours of the onset of ARDS, and and the primary outcome is mortality 28 days after randomisation. All patients will be followed up at 1 year to determine whether salbutamol treatment has any effect on the health of survivors over the subsequent year. An economic evaluation willl be conducted alongside the trial.
The BALTI 2 trial is an effectiveness study, where the allocation of salbutamol or placebo infusion is determined randomly, but all other treatment decisions are left to the clinicians managing the patient. 1344 patients will be randomised within 72 hours of the onset of ARDS, and and the primary outcome is mortality 28 days after randomisation. All patients will be followed up at 1 year to determine whether salbutamol treatment has any effect on the health of survivors over the subsequent year. An economic evaluation willl be conducted alongside the trial.
Organisations
- University of Warwick, United Kingdom (Lead Research Organisation)
- National Institute for Health Research, United Kingdom (Collaboration)
- The Royal College of Anaesthetists (Collaboration)
- UK Perioperative Medicine Clinical Trials Network (Collaboration)
- Royal College of Surgeons of England, United Kingdom (Collaboration)
- NHS England, United Kingdom (Collaboration)
- National Institute of Academic Anaesthesia (Collaboration)
Publications
Zheng S
(2018)
ResolvinD stimulates epithelial wound repair and inhibits TGF-ß-induced EMT whilst reducing fibroproliferation and collagen production.
in Laboratory investigation; a journal of technical methods and pathology
Wang Q
(2014)
S102 Lipoxin A4 Improves Efferocytosis Via Inhibition Of The Hmgb1 In Human Alveolar Macrophages
in Thorax
Perkins GD
(2014)
The beta agonist lung injury trial prevention. A randomized controlled trial.
in American journal of respiratory and critical care medicine
Perkins GD
(2011)
The Beta Agonist Lung Injury TrIal (BALTI)--prevention trial protocol.
in Trials
Howes M
(2013)
The Use of Beta 2-Agonists for the Treatment of Acute Respiratory Distress Syndrome
in Journal of the Intensive Care Society
Gates S
(2013)
Beta-Agonist Lung injury TrIal-2 (BALTI-2): a multicentre, randomised, double-blind, placebo-controlled trial and economic evaluation of intravenous infusion of salbutamol versus placebo in patients with acute respiratory distress syndrome.
in Health technology assessment (Winchester, England)
Gao Smith F
(2012)
Effect of intravenous ß-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial.
in Lancet (London, England)
Bassford CR
(2012)
The rise and fall of ß-agonists in the treatment of ARDS.
in Critical care (London, England)
| Guideline Title | The International Surviving Sepsis Campaign Guidelines for management of severe sepsis and septic shock 2012 |
| Description | Change the International Surviving Sepsis Campgain Guidelines |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | Salbutamol infusion resulted in a 10.8% increase in 28-day mortality, which means that every 9 ARDS patients treated with salbutamol would result in one extra death. Consistent with 28-day mortality, there was a 8.4% increase in ICU mortality and 6% increase in hospital mortality in the salbutamol arm although this did not reach statistical significance. Again consistent with mortality data, salbutamol group had the mean 2.68 day reduction in ventilator-free days, and the mean 2.3 organ free days compared with the placebo arm. ARDS survivors in salbutamol group required average 3.4 more days in ICU than placebo arm and this nearly reached a statistical significance. We did not find a significant difference between two groups in length of ICU and hospital stay, in level 3 care bed days. The data suggested that quality of life was lower in the salbutamol group. Health economic analyses showed that costs of care were slightly higher in the salbutamol group and that salbutamol was unlikely to be cost-effective. However, our snapshot audit in 2013 showed beta-2 agonists were still used as one of drug treatments for ARDS: 8% in the UK and 14% in China patients with ARDS. |
| URL | http://inc.sagepub.com/content/14/3/196.full.pdf |
| Description | Citation in Editorial, Lancet with the publication on our trial. |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in other policy documents |
| Impact | International practice on use of Beta-2 agonists in critically ill patients. |
| URL | http://www.ncbi.nlm.nih.gov/pubmed/22166901 |
| Guideline Title | Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 |
| Description | Our findings of Balti-2 trial provided the good evidence for revised International Guideline for Sepsis Management 2017 |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | provided the scientific evidence for the guideline update. |
| URL | http://www.survivingsepsis.org/Guidelines/Pages/default.aspx |
| Description | BALTI II treatment costs subvention |
| Amount | £178,000 (GBP) |
| Organisation | Department of Health (DH) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2007 |
| End | 09/2009 |
| Description | The Beta Agonist Lung Injury Trial (prevention) : BALTI-prevention study |
| Amount | £248,983 (GBP) |
| Funding ID | PB-PG-0408-16104 |
| Organisation | National Institute for Health Research |
| Department | Research for Patient Benefit |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2009 |
| End | 07/2012 |
| Description | a feasibility study for BALTI II |
| Amount | £50,000 (GBP) |
| Organisation | Intensive Care Foundation (ICF) |
| Sector | Private |
| Country | Australia |
| Start | 01/2006 |
| End | 01/2007 |
| Description | IMPACT Study |
| Organisation | National Institute for Health Research |
| Department | NIHR Clinical Research Network (CRN) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I had the original idea on evaluating IMPACT of UK critical care RCTs which was accepted by the Intensive Care Foundation and NIHR CRN for Critical Care specialty. Dr Jaimin Patel, Clinician Scientist, University of Birmingham (from my team) under my and Dr Paul Dark (Prof in University of Manchester) supervision leads this prospective national evaluation of impact of these RCTs (including Balti-2) on changes of clinical practice. |
| Collaborator Contribution | Professor Paul Dark, Chair of the NIHR Critical Care CRN, supported the idea, contributed to the protocol and supported to obtain a CRN funding £5000 for the study, |
| Impact | 1. to raise awareness in the UK critical care community on impact of clinical research; 2. to evaluate the outputs and outcomes of the UK Intensive Care Foundation funded clinical trials. |
| Start Year | 2015 |
| Description | collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs |
| Organisation | NHS England |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Collaborator Contribution | Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Impact | Further £2,000,000 funding received. |
| Start Year | 2018 |
| Description | collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs |
| Organisation | National Institute of Academic Anaesthesia |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Collaborator Contribution | Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Impact | Further £2,000,000 funding received. |
| Start Year | 2018 |
| Description | collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs |
| Organisation | Royal College of Surgeons of England |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Collaborator Contribution | Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Impact | Further £2,000,000 funding received. |
| Start Year | 2018 |
| Description | collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs |
| Organisation | The Royal College of Anaesthetists |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Collaborator Contribution | Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Impact | Further £2,000,000 funding received. |
| Start Year | 2018 |
| Description | collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs |
| Organisation | UK Perioperative Medicine Clinical Trials Network |
| Sector | Academic/University |
| PI Contribution | Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Collaborator Contribution | Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Impact | Further £2,000,000 funding received. |
| Start Year | 2018 |
| Description | collaborations with other universities, NHS organisations, NIHR CRN, Royal College of Anaesthetists, Royal College of Surgeons, Research Trainees network, UK Perioperative Medicine Clinical Trials Network, NIAA, ACTAC, NIAA HSRC PCPIE and PPIs |
| Organisation | UK Perioperative Medicine Clinical Trials Network |
| Sector | Academic/University |
| PI Contribution | Assisted co-applicants with expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Collaborator Contribution | Co-applicants contributed expertise from different institutions, active contributions to economic growth and increase influence of PPIs and strengthen trainee research networks. |
| Impact | Further £2,000,000 funding received. |
| Start Year | 2018 |
| Description | 12th Annual Critical Care Symposium, April 2015, Manchester England |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The faculties of the Symposiums are from the best researchers and the best policy makers in critical care communities, and it was great honour to be a part of it. More than 500 participants from all over the world attended this annual event for the purpose of receiving the most updated research information on use of beta-agonists in ARDS patients which sparked questions and debates. |
| Year(s) Of Engagement Activity | 2014,2015,2016 |
| URL | http://critcaresymposium.co.uk/site3/ |
| Description | 14TH ANNUAL CRITICAL CARE SYMPOSIUM |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | International speakers in the critical care area to demonstrate expertise to inspire further excellent research. |
| Year(s) Of Engagement Activity | 2018 |
| Description | 29th and 30th Internaitonal Symposium of Intensive Care and Emegency Medicine, Brussels, Belgium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | More than thousands participants attended symposium each year to take in newly released clinical research information. |
| Year(s) Of Engagement Activity | 2009,2010 |
| URL | http://www.ccforum.com/supplements/all |
| Description | ? 16th World Congress of Anaesthesiology, Hong Kong |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Should we be using beta agonists in ARDS? |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://wca2016.com/ |
| Description | ? International Clinical Trial Conference July 2015, Orlando, Florida, USA |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Exchanged experience in how to handle a premature terminated clinical trial. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://clinicaltrials.conferenceseries.com/2015 |
| Description | Annual Scientific Meeting on Intensive Care 2018, Kuala Lumpur, 21-23 Sept, 2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Enhance our international collaborations in research and education with he final goal to improve the patients care and outcomes. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Intensive Care Society UK State of Art Conference 2011, London |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Approximately 500 participants attended the Conference to take in the BALTI-2 findings prior to the publication, which stimulated loads of questions and discussions amongst the community. |
| Year(s) Of Engagement Activity | 2011 |
| URL | http://www.ics.ac.uk/ics-homepage/events/past-meetings/state-of-the-art-meeting-2011/ |
| Description | Trial of drug for acute respiratory distress syndrome stopped following increased mortality and no improvement in outcomes (BALTI-2 study)-Press Release |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Intensive Care community in the world received the Release, which stimulated questions and discussions afterwards, and the Society applied the evidence into the Guideline to change ICM clinicians practice. |
| Year(s) Of Engagement Activity | 2011 |
| URL | http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61623-1/abstract |
| Description | Wessex CRN annual conference, Basingstoke, Hampshire, England, Nov 2017 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | The feedback to my presentation on our success in trial recruitment: such inspiration presentation and could we put your presentation at our CRN portal? |
| Year(s) Of Engagement Activity | 2017 |
| Description | dissemination to participants |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Type Of Presentation | Keynote/Invited Speaker |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Surviving participants informed of publication of the trial's results by post. None yet. |
| Year(s) Of Engagement Activity | 2011 |