Post-operative complications - Post-operative Pulmonary complication, Acute Respiratory Distress Syndrome and Myocardial Infarction
Conditions
Interventions
Product Name: Simvastatin
Pharmaceutical Form: Tablet
INN or Proposed INN: Simvastatin
CAS Number: 79902-63-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Ph
Sponsors
Belfast Health and Social Care Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Adult patients =18 years of age undergoing elective oesophagectomy 2.Female subjects must be surgically sterile, or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 30 days after completion of treatment. A pregnancy test, measured by urine HCG in females with child bearing potential, will be performed at pre-operative assessment clinic Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 252 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 1.Age 5 times upper limit normal range in the local laboratory 3.Known active liver disease (Child’s Pugh score > 11) or abnormal liver function tests i.e. transaminases (AST or ALT) > 3 times upper limit normal range in the local laboratory 4.Renal impairment (calculated creatinine clearance less than 30mL/minute) 5.Inability to take oral medication pre-operatively 6.Subject reported lactose intolerance 7.Participation in other intervention trials within 30 days. 8.Current treatment with statins 9.Known hypersensitivity to the study medication 10.Previous adverse reaction to statins 11.Concomitant use of fibrates or other lipid-lowering therapy 12.Concomitant use of itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprivir, telaprevir, nefazodone, cyclosporine, danazol, amiodarone, amlodipine, verapamil or diltiazem, fusidic acid 13.Patients must be able to understand and give signed and dated informed consent indicating that they understand all the pertinent aspects of the trial prior to enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal research question is whether treatment with simvastatin when compared to a placebo (dummy pill) reduces complications related to the heart and lungs after oesophagectomy (surgery to remove the food pipe). Patients who undergo oesophagectomy receive ventilation (breathing support) to one lung while the other lung is allowed to collapse down. This will allow access to the foodpipe and this is a major surgery. The ventilation of one lung can lead to stretch of one lung while the other lung will be collapsed down. Both stretch and collapse can lead to inflammation and these patients have a high incidence of lung related complications such as pneumonia and in a more severe situation a condition called acute respiratory distress syndrome (ARDS). They also have a significant stress on the heart which can cause heart attacks (myocardial ischaemia). Various smaller studies have shown that patients who are on the group of medications called statins (to which the study drug si;Secondary Objective: The secondary research questions will look at the following: 1. Chances of complications such as post surgical lung complications and heart attacks up to 28 days post surgery or hospital discharge whichever is earlier 2. Abnormal heart rhythm by day 28 or hospital discharge whichever is earlier 3. Clots in deep veins by day 28 or hospital discharge whichever is earlier 4. Surgical complications by day 28 or hospital discharge whichever is earlier 5. Duration for which breathing support was used after surgery 6. Safety of the study drug as measured by liver, kidney function and muscle enzyme 7. Health related quality of life (HRQoL) 8. Length of ICU stay (level 3 care) 9. Length of HDU stay (level 2 care) 10. Length of hospital stay 11. Health service contacts up to 90 days post surgery 12. Cost effectiveness of the study drug 13. Hospital mortality and 90 day mortality ;Primary end point(s): The primary outcome measure is a composite endpoint of the i | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcomes include clinical outcomes, safety and data for the economic evaluation. Clinical Outcomes 1. Mortality at day 28 and day 90 2. Ventilator free days (VFDs) and are defined as the number of days in the first 28 days following surgery that a patient is free from ventilator assistance, for greater than 48 hrs. 3. ARDS, PPC and MI within 28 days of surgery or hospital discharge if earlier 4. Atrial fibrillation within 28 days of surgery or hospital discharge if earlier 5. Venous thromboembolism within 28 days of surgery or hospital discharge if earlier 6. Incidence and nature of any surgical complications will be recorded Safety 1. CK >10 times the upper limit of normal (day 0, day 3 and day 7 post-surgery) 2. ALT/AST >5 times the upper limit of normal (day 0, day 3 and day 7 post-surgery) 3. Serious adverse events (SAEs), adverse events(AEs) and occurrence of suspected unexpected serious adverse reactions (SUSARs) Health Economic Outcomes 1. Health related quality of life (HRQoL): • EQ-5D-5L at randomisation and at 90 days post-surgery. 2. Health and Social Care Service Use: • Length of ICU stay (level 3 care) • Length of HDU stay (level 2 care) • Length of hospital stay • Health service contacts up to 90 days post-surgery ;Timepoint(s) of evaluation of this end point: Patients will be followed up after their oesophagectomy for the evaluation of their secondary endpoints 1. Clinical secondary endpoints will be evaluated till day 28 post surgery or till hospital discharge whichever is earlier 2. Data for health economic evaluation will be collected by administration of the health related quality of life questionnaire (EQ-5D-5L) at baseline and at 90 days after surgery. Health resource utilisation data will be collected at day 90 post surgery. We will also collect data regarding their use of level 3, level 2 care and also the hospital length of stay as part of healthcare utilisation data. | — |
Countries
United Kingdom
Contacts
Public ContactDr Murali Shyamsundar
The Queen's University of Belfast
Outcome results
None listed