Simvastatin to prevent complications after oesophagectomy v1.0
Research type
Research Study
Full title
Prevention of post-operative complications by using HMG-CoA Reductase Inhibitor in patients undergoing oesophagectomy - A multicentre, randomised, double blind, placebo controlled trial
IRAS ID
180853
Contact name
Murali Shyamsundar
Contact email
Sponsor organisation
Belfast Health and Social Care Trust
Eudract number
2015-004424-65
Duration of Study in the UK
4 years, 2 months, 9 days
Research summary
Oesphagectomy (removal of food pipe) is a common surgery. 1220 oesophagectomies were performed in 2013 in England and Wales. One in three patients will develop complications. Heart and lung complications account for up to 50% of complications requiring admissions to Intensive Care Units (ICUs). The risk of dying is significantly elevated in these patients when compared to patients who do not suffer these complications. There is also an impact on their long term disability as these patients have physical and mental health issues. There is also a reduced rate of return to employment. There is no proven pharmacotherapy to reduce these complications in patients undergoing oesophagectomy.
In addition, there is an associated increase in healthcare utilisation costs. ICU is an expensive and limited resource and a bed in ICU costs up to £1500. These patients also have a higher rate of healthcare contacts after discharge.
Simvastatin belongs to a group of medications licensed to reduce fat levels in the blood. Simvastatin, through its enzyme blocking action, has also been shown to reduce inflammation and reduce cell damage. In various studies it has been shown to reduce the rates of progression of severe infection, death from sepsis, ICU admissions and to be cardioprotective. In a small study conducted by our team, we have shown that simvastatin reduces inflammation in the lungs and reduces the rates of heart, lung and infective complications.
Based on our studies and other published evidence, we will conduct this multi-centre trial to study the benefits of giving simvastatin to patients before their surgery to reduce heart and lung complications. Simvastatin is a cheap drug and costs less than £5 for the proposed treatment. If proven beneficial, this study has the potential to improve both patient outcomes and reduce costs to the NHS.
Research Summary:
When a patient gets surgery for removal of the food pipe or removal of a lung or part of a lung they could develop complications after surgery involving their lungs (postoperative pulmonary complication) which if severe can lead to ‘’acute respiratory distress syndrome” (ARDS) or have heart complications such as heart attack. Patients who develop these complications have longer lengths of stay in the hospital, higher number of admissions to the intensive care unit and have a lower chance of survival when compared to patients who do not develop these complications. There is some evidence that treatment with statins (a group of medications used to control cholesterol) before and after surgery may help to prevent these complications by modifying the inflammatory processes that underlie them.
There were no trials studying the effectiveness of statins in patients undergoing surgery for removal of food pipe or removal of a lung or part of a lung and so the Prevention Harp-2 trial was undertaken to test the hypothesis that treatment with simvastatin 80mg once daily for four days pre-surgery and up to 7 days post-surgery will prevent cardiac and respiratory complications in participant undergoing these surgeries. The study aimed to enrol 452 participants however the study closed early to recruitment and only 251 were recruited; 126 treated with simvastatin daily and 125 treated with placebo or dummy drug, which had no active ingredients.
The results of the Prevention Harp-2 trial showed that at 7 days after surgery there was no difference in the number of post-operative complications between participants in the simvastatin and placebo groups. So simvastatin did not have an effect. There were no other clinical differences between the two groups either. Slightly lower healthcare costs were seen in participants in the simvastatin group, but also slightly lower health-related quality of life over 90 days. It was found that simvastatin was still likely to be cost-effective compared with placebo because cost savings outweighed any loss in quality of life.REC name
South Central - Berkshire Research Ethics Committee
REC reference
16/SC/0152
Date of REC Opinion
24 Mar 2016
REC opinion
Favourable Opinion