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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Örebro University, Sweden
Sponsor:
Collaborator:
University Hospital, Linkoeping
Information provided by (Responsible Party):
Anil Gupta, Örebro University, Sweden
ClinicalTrials.gov Identifier:
NCT01318161
First received: March 17, 2011
Last updated: May 25, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Pain
Other Complications
Drug: Ropivacaine + opioid epidurally
Drug: Morphine
Phase 3

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Örebro University, Sweden:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 300
Study Start Date: March 2011
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01318161

Locations
Sweden
University Hospital Recruiting
Linköping, Sweden, 581 85
Contact: Christina Eintrei, MD, PhD    +46 0101031835    christina.eintrei@lio.se   
University Hospital Recruiting
Örebro, Sweden, 701 85
Contact: Anil Gupta, MD, FRCA, PhD    +46 19 6020256    anil.gupta@orebroll.se   
Sponsors and Collaborators
Örebro University, Sweden
University Hospital, Linkoeping
  More Information

No publications provided

Responsible Party: Anil Gupta, Associate Professor, Örebro University, Sweden
ClinicalTrials.gov Identifier: NCT01318161     History of Changes
Other Study ID Numbers: 2010/415-31
Study First Received: March 17, 2011
Last Updated: May 25, 2014
Health Authority: Sweden: S-Huset University Hospital
Sweden: Clinical Research Support
Sweden: Örebro

Keywords provided by Örebro University, Sweden:
Epidural analgesia
Patient controlled analgesia
Colorectal cancer
Morbidity
Mortality

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Morphine
Analgesics, Opioid
Ropivacaine
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Local
Anesthetics

ClinicalTrials.gov processed this record on August 19, 2014