Regional Anesthesia and Endometrial Cancer Recurrence

NCT ID: NCT00531349

Last Updated: 2016-05-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2007-11-30

Brief Summary

The purpose of this study is to determine whether recurrence of local and metastatic cancer after open hysterectomy for stage 1 or 2 endometrial cancer is reduced when patients receive epidural anesthesia/analgesia combined with propofol sedation rather than sevoflurane anesthesia and opioid analgesia.

Detailed Description

This is a Phase III, multi-center study of patients having open hysterectomies for endometrial cancer. Patients will be randomly assigned to 1) epidural anesthesia/analgesia with propofol sedation; or 2) general anesthesia combined with postoperative patient-controlled morphine analgesia. There will be a total (maximum) of 1700 patients enrolled over a 5 year enrollment.

All patients will be premedicated with 1-3 mg IV midazolam and 1-2 µg/kg fentanyl. Patients will be randomly assigned to epidural anesthesia & analgesia with propofol sedation or to sevoflurane general anesthesia and postoperative opioid analgesia after they have met the inclusion/exclusion criteria and consent to the study.

In patients assigned to general anesthesia and opioid analgesia (General Anesthesia Group), general anesthesia will be induced with 1-3 µg/kg fentanyl and 2-4 mg/kg propofol. Tracheal intubation will be facilitated by succinylcholine or a non-depolarizing muscle relaxant; alternatively, a supraglottic airway (such as a laryngeal mask) will be used. Additional non-depolarizing muscle relaxant will be administered as deemed necessary by the attending anesthesiologist.

Anesthesia will be maintained with sevoflurane in 80% oxygen, balance nitrogen, and fentanyl. Sevoflurane and fentanyl administration will be adjusted to maintain blood pressure and heart rate within 20% of pre-operative values. The lungs will be mechanically ventilated to maintain end-tidal PCO2 near 35 mm Hg. When surgery is complete, muscle relaxant will be antagonized, if necessary, and the trachea extubated. Post-operative analgesia will be morphine, provided as needed IV or via patient-controlled pump. The initial pump setting will be for 1 mg boluses with a 6-minute lockout period and no background infusion. Additional morphine will be provided as necessary to maintain good pain control, either as needed or by changing the pump settings. Morphine will be the first-line drug; but hydromorphone will be substituted at one-fifth the morphine dose in patients who do not tolerate morphine. When pain is adequately controlled without much morphine (usually on the second postoperative day), patients will be transitioned to acetaminophen and non-steroidal anti-inflammatory analgesics; oral opioids will also be permitted if necessary.

In the Epidural Anesthesia and Analgesia group, a T8-10 epidural catheter will be inserted using a standard technique. After negative aspiration for blood, patients will be given a test dose of 3 ml of 1.5% lidocaine and 1:200,000 epinephrine. The catheter will be re-inserted or repositioned as necessary until both aspiration and test dose are negative. Each patient will be given an additional 12-18 ml bolus of 0.5% bupivacaine or 0.5% ropivacaine to provide intraoperative analgesia. The catheter will be repositioned or reinserted as necessary if a sensory block to temperature cannot be confirmed in the surgical dermatomes. Additional 5-10 ml boluses of the same solution will be given hourly during surgery to maintain anesthesia; additional boluses will be permitted at the discretion of the attending anesthesiologist.

Postoperative epidural analgesia will be supplemented with acetaminophen and/or NSAIDs if needed, or per individual sites' routine protocol. Supplemental morphine will be provided only if pain relief is inadequate, either "as needed" or by patient-controlled infusion. As soon as practical, usually on the second postoperative day, patients will be transitioned to acetaminophen and/or non-steroidal analgesics and, if necessary, oral opioids.

Conditions

Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

A

General anesthesia and opioid analgesia for the treatment of pain after surgery.

Group Type: ACTIVE_COMPARATOR

Sevoflurane

Intervention Type: DRUG

General anesthesia

B

Regional anesthesia and analgesia (epidural) combined with deep sedation or general anesthesia.

Group Type: ACTIVE_COMPARATOR

propofol general anesthesia

Intervention Type: PROCEDURE

Regional analgesia combined with sedation or a propofol general anesthesia

Interventions

propofol general anesthesia

Regional analgesia combined with sedation or a propofol general anesthesia

Intervention Type: PROCEDURE

Sevoflurane

General anesthesia

Intervention Type: DRUG

Other Intervention Names

propofol

Eligibility Criteria

Inclusion Criteria

1. Primary endometrial cancer without known extension beyond the uterus i.e., believed to be Stage 1 or 2

2. Scheduled for open abdominal hysterectomy

3. Written informed consent, including willingness to be randomized epidural anesthesia/analgesia with sedation or to sevoflurane general anesthesia and postoperative opioid analgesia

Exclusion Criteria

1. Previous surgery for endometrial cancer

2. Any contraindication to epidural anesthesia or analgesia (including coagulopathy, abnormal anatomy)

3. Any contraindication to midazolam, propofol, sevoflurane, fentanyl, or morphine

4. Age < 18 or > 85 years old

5. ASA Physical Status ≥ 4

6. Any contraindication to epidural anesthesia and analgesia (including coagulopathy, abnormal anatomy)

7. Other cancer not believed by the attending surgeon to be in long-term remission

8. Systemic disease believed by the attending surgeon or anesthesiologist to present ≥ 25% two-year mortality

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Cleveland Clinic

Principal Investigators

Daniel I. Sessler, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Daniel I. Sessler, MD

Role: STUDY_CHAIR

The Cleveland Clinic

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

07-532

Identifier Type: -

Identifier Source: org_study_id