Regional Anesthesia and Endometrial Cancer Recurrence (ECA/R)

• ClinicalTrials.gov Identifier: NCT00531349
• Recruitment Status: Withdrawn
• First Posted: September 18, 2007
• Last Update Posted: May 9, 2016
• Sponsor: The Cleveland Clinic
• Information provided by: The Cleveland Clinic

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cancer	Procedure: propofol general anesthesia; Drug: Sevoflurane	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Regional Anesthesia and Endometrial Cancer Recurrence
• Study Start Date: November 2007
• Actual Primary Completion Date: November 2007
• Actual Study Completion Date: November 2007

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: A; General anesthesia and opioid analgesia for the treatment of pain after surgery.	Drug: Sevoflurane; General anesthesia
Active Comparator: B; Regional anesthesia and analgesia (epidural) combined with deep sedation or general anesthesia.	Procedure: propofol general anesthesia; Regional analgesia combined with sedation or a propofol general anesthesia; Other Name: propofol

Outcome Measures

Primary Outcome Measures :

1. Time to metastatic spread or local cancer recurrence [ Time Frame: every six months throughout the study, yearly thereafter ]

Secondary Outcome Measures :

1. Any-cause mortality [ Time Frame: 4.4 years, 6.0 years, 7.5 years and if needed 8.9 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44129

Sponsors and Collaborators

The Cleveland Clinic

Investigators

• Principal Investigator: Daniel I. Sessler, MD; The Cleveland Clinic
• Study Chair: Daniel I. Sessler, MD; The Cleveland Clinic

More Information

• Responsible Party: Daniel I. Sessler, MD, Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT00531349 History of Changes
• Other Study ID Numbers: 07-532
• First Posted: September 18, 2007
• Last Update Posted: May 9, 2016
• Last Verified: May 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by The Cleveland Clinic:

Endometrial Cancer; Anesthesia; regional; cancer recurrence; Analgesia; opioid

Additional relevant MeSH terms:

Endometrial Neoplasms; Recurrence; Disease Attributes; Pathologic Processes; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Anesthetics; Propofol; Sevoflurane; Central Nervous System Depressants; Physiological Effects of Drugs; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Platelet Aggregation Inhibitors; Anesthetics, Inhalation