Clinical trial NCT00531349: Regional Anesthesia and Endometrial Cancer Recurrence
Official title: Regional Anesthesia and Endometrial Cancer Recurrence
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Cancer
Keywords: Endometrial Cancer
Anesthesia; regional
cancer recurrence
Analgesia; opioid
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2007-09-18
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Time to metastatic spread or local cancer recurrence
timeFrame: every six months throughout the study, yearly thereafter
Secondary outcomes:
measure: Any-cause mortality
timeFrame: 4.4 years, 6.0 years, 7.5 years and if needed 8.9 years
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Daniel I. Sessler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Daniel I. Sessler, MD
role: STUDY_CHAIR
References: