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Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

Prevention of post-operative complications by using a HMG-CoA reductase inhibitor in patients undergoing one-lung ventilation for non-cardiac surgery: study protocol for a randomised controlled trial

Authors: Murali Shyamsundar, Cecilia O’Kane, Gavin D. Perkins, Gavin Kennedy, Christina Campbell, Ashley Agus, Glenn Phair, Danny McAuley

Published in: Trials | Issue 1/2018

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Abstract

Background

Postoperative pulmonary complications (PPC) and peri-operative myocardial infarction (MI) have a significant impact on the long-term mortality of surgical patients. Patients undergoing one-lung ventilation (OLV) for surgery are at a high risk of developing these complications. These complications could be associated with intensive care unit (ICU) admissions and longer hospital stay with associated resource and economic burden. Simvastatin, a HMG-CoA reductase enzyme inhibitor has been shown to have pleiotropic anti-inflammatory effects as well as being endothelial protective. The benefits of statins have been shown in various observational studies and in small proof-of-concept studies. There is an urgent need for a well-designed, large clinical trial powered to detect clinical outcomes. The Prevention HARP 2 trial will test the hypothesis ‘simvastatin 80 mg when compared to placebo will reduce cardiac and pulmonary complications in patients undergoing elective oesophagectomy, lobectomy or pneumonectomy’.

Methods/design

The Prevention HARP 2 trial is a UK multi-centre, randomised, double-blind, placebo-controlled trial. Adult patients undergoing elective oesophagectomy, lobectomy or pneumonectomy will be eligible. Patients who are already on statins will be excluded from this trial. Patients will be randomised to receive simvastatin 80 mg or matched placebo for 4 days pre surgery and for up to 7 days post surgery. The primary outcome is a composite outcome of PPC and MI within 7 days post surgery. Various secondary outcome measures including clinical outcomes, safety outcomes and health economic outcomes will be collected. The study aims to recruit 452 patients in total across 12 UK sites.

Discussion

The results of the Prevention HARP 2 trial should add to our understanding of the benefits of peri-operative statins and influence clinical decision-making. Analysis of blood and urine samples from the patients will provide insight into the mechanism of simvastatin action.

Trial registration

International Standard Randomised Controlled Trials registry, ID: ISRCTN48095567. Registered on 11 November 2016.
Appendix
Available only for authorised users
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Metadata
Title
Prevention of post-operative complications by using a HMG-CoA reductase inhibitor in patients undergoing one-lung ventilation for non-cardiac surgery: study protocol for a randomised controlled trial
Authors
Murali Shyamsundar
Cecilia O’Kane
Gavin D. Perkins
Gavin Kennedy
Christina Campbell
Ashley Agus
Glenn Phair
Danny McAuley
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-3078-5

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