Epidural Anesthesia-analgesia and Long-term Survival After Lung Cancer Surgery

Sponsor

Peking University First Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02801409

Collaborator

(none)

400

Enrollment

Location

Arms

54.2

Actual Duration (Months)

7.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Available studies suggest that regional anesthesia-analgesia may decrease the occurrence of recurrence/metastasis in patients after cancer surgery. However, evidences from prospective studies are still lacking. The purpose of this randomized controlled trial is to investigate the effect of epidural anesthesia-analgesia on recurrence-free survival in patients undergoing lung cancer surgery.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer Thoracic Surgery Anesthesia, Epidural Neoplasm Recurrence, Local Neoplasm Metastasis	Drug: General anesthesia alone Drug: Combined epidural-general anesthesia	N/A

Detailed Description

Lung cancer is increasing and is the leading cause of cancer death. Surgical resection is the mainstay of treatment for early stage non-small cell lung cancer. However, long-term survival after lung cancer surgery is far from optimal, and cancer recurrence or metastasis is the main reason leading to cancer death in these patients.

The development of cancer recurrence/metastasis largely depends on the balance between tumor-promoting factors and immune function of the body. Studies showed that surgical manipulation releases cancer cells into circulation; and stress response induced by surgery inhibits the cell-mediated immunity. In addition, volatile anesthetics and opioids may also aggravate immunosuppression and potentially worsen long-term outcome. On the other hand, regional anesthesia can blunt surgical stress and reduce anesthetic consumption. These effects may help to preserve immune function and reduce recurrence/metastasis. However, existing evidences are insufficient to draw conclusion in this topic.

The purpose of this randomized controlled trial is to test the hypothesize that regional anesthesia-analgesia may reduce recurrence/metastasis and improve long-term survival in patients after lung cancer surgery.

Study Design

Study Type:

Interventional

Actual Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Effects of Epidural Anesthesia-analgesia on Long-term Survival in Patients After Lung Cancer Surgery: A Randomized Controlled Trial

Actual Study Start Date :

May 25, 2015

Actual Primary Completion Date :

Nov 11, 2017

Actual Study Completion Date :

Nov 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: General anesthesia alone General anesthesia is performed during surgery; patient-controlled intravenous analgesia is provided after surgery.	Drug: General anesthesia alone General anesthesia is performed during surgery; patient-controlled intravenous analgesia is provided after surgery.
Experimental: Combined epidural-general anesthesia Combined epidural-general anesthesia is performed during surgery; patient-controlled epidural analgesia is provided after surgery.	Drug: Combined epidural-general anesthesia Combined epidural-general anesthesia is performed during surgery; patient-controlled epidural analgesia is provided after surgery.

Arm

Intervention/Treatment

Active Comparator: General anesthesia alone

General anesthesia is performed during surgery; patient-controlled intravenous analgesia is provided after surgery.

Drug: General anesthesia alone

General anesthesia is performed during surgery; patient-controlled intravenous analgesia is provided after surgery.

Experimental: Combined epidural-general anesthesia

Combined epidural-general anesthesia is performed during surgery; patient-controlled epidural analgesia is provided after surgery.

Drug: Combined epidural-general anesthesia

Combined epidural-general anesthesia is performed during surgery; patient-controlled epidural analgesia is provided after surgery.

Outcome Measures

Primary Outcome Measures

Recurrence-free survival after surgery. [Up to 4 years after surgery.]
Time from surgery to the earliest date of recurrence/metastasis or death from any cause, whichever came first.

Secondary Outcome Measures

Rate of intensive care unit admission after surgery. [Up to 30 days after surgery.]
Rate of intensive care unit admission after surgery.
Incidence of postoperative complications during hospital stay. [Up to 30 days after surgery.]
Postoperative complications are defined as new-onset conditions that are harmful to patients' recovery and required therapeutic intervention, i.e., class II or higher on the Clavien-Dindo classification.
Duration of chest tube placement. [Up to 30 days after surgery.]
Duration of chest tube placement.
Length of stay in hospital after surgery. [Up to 30 days after surgery.]
Length of stay in hospital after surgery.
Rate of all-cause mortality during hospital stay after surgery. [Up to 30 days after surgery.]
Rate of all-cause mortality during hospital stay after surgery.
Overall survival rate after surgery. [Up to 4 year after surgery.]
Time from surgery to all-cause death.
Cancer-specific survival after surgery. [Up to 4 years after surgery.]
Time from surgery to cancer-specific death; deaths from other causes are censored at the time of death.
Activity engagement in 1-year survivors. [At the end of the first year after surgery.]
Activity engagement is assessed by estimating metabolic equivalents (METs; 1 MET = 3·5 ml/min/kg resting oxygen consumption) for activity in daily life.

Other Outcome Measures

Pain intensity after surgery. [During the first 3 days after surgery.]
Assessed with the numeric rating score, an 11-point scale where 0 = no pain and 10 = the most severe pain.
Recurrence-free survival in cancer patients. [Up to 4 years after surgery.]
Time from surgery to the earliest date of recurrence/metastasis or death from any cause, whichever came first.
Overall survival in cancer patients. [Up to 4 years after surgery.]
Time from surgery to all-cause death.
Cancer-specific survival in cancer patients. [Up to 4 years after surgery.]
Time from surgery to cancer-specific death; deaths from other causes are censored at the time of death.
Number of CD8+ and FOXP3+ T cells per mm2 tumor area (sub-study). [After resection of lung adenocarcinoma specimens]
Immunohistochemical staining of CD8 and FOXP3 molecules in excised lung adenocarcinoma specimens. Performed in part of enrolled patients.
Percentage of NK-cells and T-cell subgroups in peripheral blood (sub-study). [Peripheral blood samples collected before induction, at the end of surgery and at 24 hours after surgery.]
Measured by flow cytometry. Performed in part of enrolled patients.
Rate of chronic pain at 3 month and 6 month after surgery (sub-study). [At 3 months and 6 months after surgery.]
Chronic pain is measured with the Brief Pain Inventory (BPI), neuropathic pain screening questionnaire (ID pain), and McGill Pain Questionnair (MPQ). Performed in part of enrolled patients.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients (aged 18-80 years);
Clinically diagnosed as primary non-small cell lung cancer of stage IA to IIIA, and scheduled for radical surgery;
Agreed to receive patient-controlled analgesia after surgery.

Exclusion Criteria:

Distant metastasis, malignant tumor in other organs, or chemo-/radiotherapy or other anti-cancer therapy before surgery;
Comorbid with autoimmune diseases, or glucocorticoid/immunosuppressant therapy within 1 year;
History of schizophrenia, epilepsy or Parkinson disease, or unable to complete preoperative assessment due to severe dementia, language barrier, or end-stage disease;
Severe hepatic disease (Child-Pugh classification C), renal failure (serum creatinine

442 umol/L or receiving renal replacement therapy), or American Society of Anesthesiologists classification IV or higher;

History of anesthesia and/or surgery within 1 year;
Contraindications to epidural anesthesia, including spinal deformity, coagulation dysfunction, local infection, and history of spinal trauma/surgery;
Allergic to any medications used during the study.