Epidural Versus Patient-controlled Analgesia for Reduction in Long-term Mortality Following Colorectal Cancer Surgery (EPICOL)
Drug: Ropivacaine + opioid epidurally
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Epidural or Patient-controlled Analgesia for Colorectal Cancer Surgery. Long-term Outcomes.|
- Long-term (up to 5 yrs) all-cause mortality [ Time Frame: 7 years from start of enrollment ] [ Designated as safety issue: Yes ]Cancer specific as well as all-cause mortality would be recorded.
- Cancer recurrence detected by MRI; perioperative complications [ Time Frame: 7 years following start of enrollment ] [ Designated as safety issue: Yes ]All complications during the perioperative period including cancer recurrence detected by MRI examination once each year would be recorded.
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||May 2018 (Final data collection date for primary outcome measure)|
|Experimental: Epidural anesthesia and analgesia||
Drug: Ropivacaine + opioid epidurally
Epidural analgesia with local anesthetic + opioid
|Active Comparator: Patient controlled analgesia||
Morphine via PCA pump
An application was sent to the Regional Ethics Committee at the Linköping University Hospital and the study was approved recently. Informed consent will be obtained from 300 patients (ASA status 1-3) in the age group 40-80 years who are undergoing elective surgery for colorectal cancer. The exact type of cancer, its staging, degree of spread to proximal or distant sites and the pathologic type of cancer will be recorded. Patients on chronic narcotic analgesic medication, those with known immunologic diseases, those with known allergy to LA and those where epidural catheter placement is contraindicated will be excluded. This study will be a multi-centre study in Central Sweden. Patients will be randomized to one of two groups according to a computer-generated random number: Group E - Epidural anaesthesia (EDA) or Group P - Patient-controlled analgesia (PCA).
Anaesthesia and surgery will be standardized, other than for group randomization. Surgical management of patients in the hospitals will also be standardized. Postoperative parameters will include pain intensity, rescue analgesic (morphine) consumption, surgical complications (e.g., re-operation, surgical site infection, or bleeding), other perioperative complications (e.g., deep vein thrombosis, cardiac complications, or chest infections), cancer recurrence diagnosed by CT or MRI (done yearly over 5 years) and mortality, both cancer-related and all-cause mortality. In addition, blood will be taken preoperatively for analysis of the following inflammatory and immunological markers:
VEGF will be determined in peritoneal fluid and in serum during surgery. HIF-1A will be determined by immunohistochemistry and microRNA measurements in normal and neoplastic colonic mucosa.
In addition, the microRNA mi21 will be analyzed in by quantitative reverse transcriptase-PCR in colon adenocarcinomas and adjacent non-cancerous tissues.
The CTC in whole blood (in 5-7.5 ml) will be measured with the CellSearch System, according to the manufacturer´s instructions, and the Cell Tracks Analyzer II (Cristofanilli M et al. N Engl J Med 2004:351:781-91).
Inflammatory mediator assay-ELISA Patient serum or EDTA/Heparin plasma will be assessed for cytokine levels by a Luminex multiplex assay (Human Inflammation 12-Plex kit; GM.CSF, IFN-g, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-a and VEGF from R&D system) and PGE2 levels will be measured by an ELISA kit from Cayman Chemicals Company. In addition, markers of systemic inflammatory response, including CRP, white blood cell count, differential count and total platelet count, will also be measured before and after surgery.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01318161
|Linköping, Sweden, 581 85|
|Contact: Christina Eintrei, MD, PhD +46 0101031835 firstname.lastname@example.org|
|Örebro, Sweden, 701 85|
|Contact: Anil Gupta, MD, FRCA, PhD +46 19 6020256 email@example.com|