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

Phase 3

Terminated

• Conditions: Other Complications; Colorectal Cancer; Pain
• Interventions: Drug: Ropivacaine + opioid epidurally; Drug: Morphine

• Registration Number: NCT01318161
• Lead Sponsor: Örebro University, Sweden

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.

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-03-17
• Study First Submitted QC: 2011-03-17
• Study First Posted: 2011-03-18
• Primary Completion: 2020-12
• Study Completion: 2021-01
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-15
• Last Update Posted: 2021-02-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 221

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Epidural anesthesia and analgesia	Ropivacaine + opioid epidurally	-
Patient controlled analgesia	Morphine	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University Hospital; 🇸🇪 Örebro, Sweden