Epidural Versus Patient-controlled Analgesia for Reduction in Long-term Mortality Following Colorectal Cancer Surgery (EPICOL)

Epidural or Patient-controlled Analgesia for Colorectal Cancer Surgery. Long-term Outcomes.

Colorectal cancer is one of the most common cancers in the industrialized world (12% of all cancers). In Sweden, 6000 new cases of colorectal cancer are reported each year, and almost half of these cases result in death. Several recently published retrospective studies show that regional anaesthesia (RA) can reduce cancer-related mortality following surgical treatment of colorectal, breast and prostate cancers and malignant melanoma. If these results are true, then the choice of perioperative pain management is as beneficial, or even better, than the current oncological therapies. This theory needs to be investigated in a prospective, randomized and controlled trail.

Study Overview

• Status: Terminated
• Conditions: Pain; Colorectal Cancer; Other Complications
• Intervention / Treatment: Drug: Ropivacaine + opioid epidurally; Drug: Morphine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 221
• Phase: Phase 3

Contacts and Locations

Study Locations

• Sweden
  • Linköping, Sweden, 581 85
    • University Hospital
  • Örebro, Sweden, 701 85
    • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA status 1-3
• Age group 40-80 years old
• Undergoing elective surgery for colorectal cancer

Exclusion Criteria:

• All contraindications to epidural analgesia
• Chronic opiate medication/drug abuse
• Allergy to morphine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epidural anesthesia and analgesia	Drug: Ropivacaine + opioid epidurally; Epidural analgesia with local anesthetic + opioid
Active Comparator: Patient controlled analgesia	Drug: Morphine; Morphine via PCA pump

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term (up to 5 yrs) all-cause mortality	Cancer specific as well as all-cause mortality would be recorded.	7 years from start of enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer recurrence detected by MRI; perioperative complications	All complications during the perioperative period including cancer recurrence detected by MRI examination once each year would be recorded.	7 years following start of enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammation	Perioperative cytokine concentration in blood assessed between randomised groups as well as surgical technique after 100 recruited patients	0-5 days
Postoperative pain and early recovery	Aspects of early postoperative recovery until discharge would be measured after 200 recruited patients between randomised groups as well as surgical techniques	0 - 7 days postoperatively

Collaborators and Investigators

• Sponsor: Örebro University, Sweden
• Collaborators: University Hospital, Linkoeping

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: March 17, 2011
• First Submitted That Met QC Criteria: March 17, 2011
• First Posted (Estimate): March 18, 2011

Study Record Updates

• Last Update Posted (Actual): February 16, 2021
• Last Update Submitted That Met QC Criteria: February 15, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Colorectal cancer; Epidural analgesia; Morbidity; Mortality; Patient controlled analgesia
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Ropivacaine; Morphine
• Other Study ID Numbers: 2010/415-31