Study of GSK2862277 in Subjects Undergoing Oesophagectomy Surgery

Summary

Lung injury in patients undergoing oesophagectomy may occur during surgery (peri-operatively) as a result of One Lung Ventilation (OLV) and/or during the immediate post-operative period when patients receive intensive care. This is reinforced by the observation that physiological markers of lung injury are most elevated immediately after completion of surgery, and the development of clinical Acute Respiratory Distress Syndrome (ARDS)occurs immediately post-operatively (within 72 hours of surgery), with the majority of cases reported 24-48 hours after completion of surgery. This study is designed to investigate the impact of pre-operative administration of GSK2862277 on biological and physiological markers of lung injury in patients undergoing surgical resection of oesophageal cancer in order to achieve optimal exposure at the site of injury following OLV and lung deflation. This study is a randomized placebo controlled, double-blind, multi-centre, single dose parallel group, design. There will be two treatment groups comprising one active and one placebo arm with approximately 40 patients per group. Patients enrolled in the study will be scheduled to undergo planned/elective trans-thoracic surgery for oesophagectomy. The primary endpoint for this study is the change in pulmonary vascular permeability index (PVPI) from pre-surgical levels to the end of surgery. GSK2862277 will be administered as an orally inhaled aerosol (single nebulized dose) over approximately 3 to 5 minutes (min) 1-3 hours prior to surgery. Subject will be monitored daily until discharge and followed up till day 28.

Timeline

Start

2015-04-28

Primary completion

2017-06-28

Completion

2017-06-28

Outcome

Outcome not reported

Stopped: “The study was terminated on the basis that protocol defined stopping criteria had been met.”

Publications

• Background Ryan J, Bayliffe AI, McAuley DF, Yeung J, Thickett DR, Howells PA, O'Donnell C, Vassallo AM, Wright TJ, McKie E, Hardes K, Summers C, Shields MO, Powley W, Wilson R, Lazaar AL, Fowler A, Perkins GD. A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study. Eur J Anaesthesiol. 2020 Nov;37(11):1014-1024. doi: 10.1097/EJA.0000000000001245.

Drugs

Indications