Epidural Anesthesia-analgesia and Long-term Outcome

July 6, 2020 updated by: Dong-Xin Wang, Peking University First Hospital

Impact of Epidural Anesthesia-analgesia on Long-term Outcome in Elderly Patients After Surgery: 5-year Follow-up of a Multicenter Randomized Controlled Trial

Surgical resection is one of the most important treatments for resectable cancer; on the other hand, cancer recurrence and/or metastasis are the major reasons of treatment failure. The development of recurrence/metastasis after cancer surgery mostly depends on the balance between the immunity of human body and the capability of implantation, proliferation and neovascularization of the residual cancer. Preclinical and retrospective clinical studies suggest that anaesthetic management may affect the long-term outcomes after cancer surgery. The investigators hypothesize that use of epidural anesthesia-analgesia may improve long-term survival in elderly patients after major surgery for cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Surgical resection is the main treatment for potentially curable solid organ cancer. However, it is unavoidable that some cancer cells are disseminated into the circulatory or lymphatic system during surgery. And quite a number of patients develop cancer recurrence and/or metastasis after surgery, which are associated with poor long-term outcomes. The development of cancer recurrence and/or metastasis after surgery is mostly dependent on the balance between the anti-tumor immune function of the human body and the ability of implantation, proliferation and neovascularization of the residual cancer cells.

Multiple surgical factors may influence the balance between the anti-cancer immune function and cancer recurrence. For example, the presence of the primary cancer inhibits angiogenesis, whereas cancer resection eliminates this safeguard against angiogenesis; surgical manipulation releases cancer cells into the circulation; surgery-related stress response inhibits natural killer (NK) cell activity and can promote the development of cancer metastasis; local and systemic release of growth factors during surgery may also promote cancer recurrence both locally and at distant sites.

Available studies showed that general anaesthesia/anesthetics may influence the cellular immune function and long-term outcomes. For example, it was found that ketamine and thiopental, but not propofol, suppressed NK cell activity; all three drugs caused a significant reduction in NK cell number; isoflurane and halothane inhibit interferon (IFN) stimulation of NK cell cytotoxicity; nitrous oxide interferes with DNA, purine, and thymidylate synthesis and depresses neutrophil chemotaxis; opioids have been reported to suppress cell-mediated and humoral immunity.

Considering the potential harmful effects of general anesthesia/anesthetics, there is an increasing interest on the effect of regional anaesthesia. Retrospective studies investigating the relationship between epidural anesthesia and outcome after cancer surgery gave different results. In a meta-analysis, regional anesthesia is associated with improved survival (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.74-0.96, P = 0.013), but not cancer recurrence/metastasis (HR 0.88, 95% Cl 0.64-1.22, P = 0.457). The investigators hypothesize that combined use of epidural anesthesia may produce favorable effects on the long-term survival in elderly patients undergoing major cancer surgery.

Study Type

Interventional

Enrollment (Actual)

1802

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100044
        • Peking University People's Hospital
      • Beijing, China, 100730
        • Beijing Hospital
      • Beijing, China, 100191
        • Peking University Third Hospital
      • Beijing, China, 100038
        • Beijing Shijitan Hospital
    • Beijing
      • Beijing, Beijing, China, 100034
        • Peking University First Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Elderly patients (age 60-90 years);
  • Scheduled to undergo noncardiac thoracic or abdominal surgery with an expected duration of 2 hours or longer. For those who undergo thoracoscopic or laparoscopic surgery, the expected length of incision must be 5 centimeters or more;
  • Agree to receive patient-controlled postoperative analgesia.

Exclusion Criteria:

  • Refuse to participate;
  • Previous history of schizophrenia, epilepsy or Parkinson disease, or unable to complete preoperative assessment due to severe dementia, language barrier or end-stage disease;
  • History of myocardial infarction or stroke within 3 months before surgery;
  • Presence of any contraindication to epidural anesthesia and analgesia, including abnormal vertebral anatomy, previous spinal trauma or surgery, severe chronic back pain, coagulation disorder (prothrombin time or activated partial prothrombin time longer than 1.5 times of the upper normal limit, or platelet count of less than 80 * 10^9/L), local infection near the site of puncture, and severe sepsis;
  • Severe heart dysfunction (New York Heart Association functional classification 3 or above), severe hepatic insufficiency (Child-Pugh grade C), or severe renal insufficiency (serum creatinine of 442 umol/L or above, with or without serum potassium of 6.5 mmol/L or above, or requirement of renal replacement therapy);
  • Any other conditions that are considered unsuitable for study participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Combined epidural-general anesthesia
Patients assigned to this group (experimental group) receive combined epidural-general anesthesia and postoperative patient-controlled epidural analgesia.
Drug: Combined epidural-general anesthesia
Combined epidural-general anesthesia and postoperative epidural analgesia. General anesthesia is performed as that in the general anesthesia group. Epidural anesthesia is performed with ropivacaine. Epidural analgesia is performed with a mixture of ropivacaine and sufentanil.
Other Names:
  • Combined epidural-general anesthesia and postoperative epidural analgesia
ACTIVE_COMPARATOR: General anesthesia
Patients assigned to this group (control group) receive general anesthesia and postoperative patient-controlled intravenous analgesia.
Drug: General anesthesia
General anesthesia and postoperative intravenous analgesia. General anesthesia is performed with propofol induction and propofol and/or sevoflurane maintenance. Intravenous analgesia is performed with morphine.
Other Names:
  • General anesthesia and postoperative intravenous analgesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival after surgery.
Time Frame: Up to median 5 years after surgery.
Time from surgery to the date of all-cause death.
Up to median 5 years after surgery.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival after surgery.
Time Frame: Up to median 5 years after surgery.
Time from surgery to the first date of cancer recurrence/metastasis, new onset cancer, new serious non-cancer disease, or death from any cause.
Up to median 5 years after surgery.
Cancer-specific survival after surgery.
Time Frame: Up to median 5 years after surgery.
Time from surgery to the date of cancer-specific death. Patients who die from other causes will be censored at the time of death.
Up to median 5 years after surgery.
Recurrence-free survival after surgery.
Time Frame: Up to median 5 years after surgery.
Time from surgery to the date of cancer recurrence/metastasis or all-cause death, whichever come first.
Up to median 5 years after surgery.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival after surgery (cancer patients).
Time Frame: Up to median 5 years after surgery.
Time from surgery to the date of all-cause death.
Up to median 5 years after surgery.
Event-free survival after surgery (cancer patients).
Time Frame: Up to median 5 years after surgery.
Time from surgery to the first date of cancer recurrence/metastasis, new onset cancer, new serious non-cancer disease, or death from any cause.
Up to median 5 years after surgery.
Cognitive function (3-year survivors).
Time Frame: At the end of the 3rd year after surgery.
Cognitive function is assessed with the modified Telephone Interview for Cognitive Status (TICS-m; a 12-item questionnaire that assesses global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function).
At the end of the 3rd year after surgery.
Cancer-specific survival after surgery (cancer patients).
Time Frame: Up to median 5 years after surgery.
Time from surgery to the date of cancer-specific death. Patients who die from other causes will be censored at the time of death.
Up to median 5 years after surgery.
Recurrence-free survival after surgery (cancer patients).
Time Frame: Up to median 5 years after surgery.
Time from surgery to the date of cancer recurrence/metastasis or all-cause death, whichever come first.
Up to median 5 years after surgery.
Quality of life (3-year survivors).
Time Frame: At the end of the 3rd year after surgery.
Quality of life is assessed with the World Health Organization Quality of Life-brief version (WHOQOL-BREF; a 24-item questionnaire that assesses the quality of life in physical, psychological, social relationship and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function).
At the end of the 3rd year after surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Collaborators

Peking University
Peking University People's Hospital
Peking University Third Hospital
Beijing Hospital
Beijing Shijitan Hospital, Capital Medical University

Investigators

  • Principal Investigator: Dong-Xin Wang, MD, Peking University First Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 1, 2014

Primary Completion (ACTUAL)

September 30, 2019

Study Completion (ACTUAL)

September 30, 2019

Study Registration Dates

First Submitted

December 31, 2016

First Submitted That Met QC Criteria

January 5, 2017

First Posted (ESTIMATE)

January 6, 2017

Study Record Updates

Last Update Posted (ACTUAL)

July 8, 2020

Last Update Submitted That Met QC Criteria

July 6, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PUCRP201101-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data will be provided on request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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