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

NCT ID: NCT01318161

Last Updated: 2021-02-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 221 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2021-01-31

Brief Summary

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.

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.

Conditions

Colorectal Cancer; Pain; Other Complications

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Epidural anesthesia and analgesia

Group Type: EXPERIMENTAL

Ropivacaine + opioid epidurally

Intervention Type: DRUG

Epidural analgesia with local anesthetic + opioid

Patient controlled analgesia

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

Morphine via PCA pump

Interventions

Ropivacaine + opioid epidurally

Epidural analgesia with local anesthetic + opioid

Intervention Type: DRUG

Morphine

Morphine via PCA pump

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Linkoeping

OTHER

Sponsor Role: collaborator

Örebro University, Sweden

OTHER

Sponsor Role: lead

Responsible Party

Anil Gupta

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Hospital

Linköping, , Sweden

University Hospital

Örebro, , Sweden

Countries

Sweden

Other Identifiers

2010/415-31

Identifier Type: -

Identifier Source: org_study_id