Colorectal CancerPhase 3EPICOLNCT01318161
Epidural Versus Patient-controlled Analgesia for Reduction in Long-term Mortality Following Colorectal Cancer Surgery
A Phase 3 study testing Ropivacaine + opioid epidurally and Morphine in people with Colorectal Cancer and Pain, run by Örebro University, Sweden at 2 sites in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Colorectal Cancer, Pain, Other Complications
- What is being tested?
- Ropivacaine + opioid epidurally and Morphine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 221 participants
- Where
- 2 sitesSweden
- Study dates
- Mar 2011to Jan 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ASA status 1-3
- Age group 40-80 years old
- Undergoing elective surgery for colorectal cancer
Who cannot join
- All contraindications to epidural analgesia
- Chronic opiate medication/drug abuse
- Allergy to morphine
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
University Hospital
Linköping, 581 85
University Hospital
Örebro, 701 85
About this study
Official title: 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.
Read the 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
- Being tested
- Ropivacaine + opioid epidurally, Morphine
- Keywords
- Epidural analgesia, Patient controlled analgesia, Colorectal cancer, Morbidity, Mortality
- Medical subject headings
- Colorectal Neoplasms, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ropivacaine + opioid epidurallyDrug
Epidural analgesia with local anesthetic + opioid
MorphineDrug
Morphine via PCA pump
| Study group | Role | What they receive |
|---|---|---|
| Epidural anesthesia and analgesia | Experimental | Not described Receives: Drug: Ropivacaine + opioid epidurally |
| Patient controlled analgesia | Active comparator | Not described Receives: Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Long-term (up to 5 yrs) all-cause mortality
Cancer specific as well as all-cause mortality would be recorded.
Measured: 7 years from start of enrollment
Secondary outcomes (1)
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.
Measured: 7 years following start of enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2011 (estimated)
- Study startMar 2011
- Primary completionDec 2020
- Study completionJan 2021
Why it stopped: Difficulty in recruiting
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 221 participants (actual)
Sponsor and investigators
- Lead sponsor
- Örebro University, Sweden
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Linkoeping
- Responsible party
- Principal investigator, Anil Gupta, Örebro University, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01318161
- Sponsor's protocol ID
- 2010/415-31
- Acronym
- EPICOL
- Status last verified
- Feb 2021
- First submitted
- 17 Mar 2011
- Last updated
- 16 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epidural or Patient-controlled Analgesia for Colorectal Cancer Surgery. Long-term Outcomes.
- ClinicalTrials.gov ID
- NCT01318161
- Acronym / sponsor ID
- EPICOL / 2010/415-31
- Conditions
- Colorectal Cancer, Pain, Other Complications
- Keywords
- Epidural analgesia, Patient controlled analgesia, Colorectal cancer, Morbidity, Mortality
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty in recruiting
- Enrolment
- 221 participants (actual)
- Lead sponsor
- Örebro University, SwedenUniversity, hospital or other
- Collaborators
- University Hospital, Linkoeping
- Study start
- Mar 2011
- Primary completion
- Dec 2020 (actual)
- Study completion
- Jan 2021 (actual)
- First posted
- 18 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Epidural anesthesia and analgesia | Experimental | Drug: Ropivacaine + opioid epidurally |
| Patient controlled analgesia | Active comparator | Drug: Morphine |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- ASA status 1-3
- Age group 40-80 years old
- Undergoing elective surgery for colorectal cancer
Key exclusion criteria (3 listed)
- All contraindications to epidural analgesia
- Chronic opiate medication/drug abuse
- Allergy to morphine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ropivacaine + opioid epidurallyEpidural analgesia with local anesthetic + opioid | Drug | Epidural anesthesia and analgesia |
| MorphineMorphine via PCA pump | Drug | Patient controlled analgesia |
Primary outcome
Long-term (up to 5 yrs) all-cause mortality
Time frame: 7 years from start of enrollment
Cancer specific as well as all-cause mortality would be recorded.
1 secondary outcome
Cancer recurrence detected by MRI; perioperative complications
Time frame: 7 years following start of enrollment
Results and safety
The study was stopped early (reason given: Difficulty in recruiting). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ropivacaine + opioid epidurally and Morphine in people with Colorectal Cancer and Pain, run by Örebro University, Sweden at 2 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulty in recruiting). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Long-term (up to 5 yrs) all-cause mortality (time frame: 7 years from start of enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2021.