Methadone and Hydromorphone For Spinal Surgery

NCT ID: NCT02107339

Last Updated: 2019-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2017-09-30

Brief Summary

Patients undergoing major spinal surgery continue to experience moderate-to-severe pain during the first 2-3 days following the operative procedure. Pain complicates the recovery process, despite the routine practice of using potent opioid analgesics. The primary reason that pain is poorly controlled in patients undergoing major surgery is that most commonly-used opioids only produce analgesia for 2-4 hours. The intermittent use of these drugs results in periods of time when a patient will experience discomfort (at which time a nurse administers more drug or the button on a patient-controlled analgesic (PCA) system is pressed to deliver more medication). The use of a long-acting opioid may be advantageous in the perioperative setting. Methadone is an opioid that has a median duration of analgesia of 24-36 hours. Therefore, a single dose administered in the operating room may reduce the need for pain medication and improve pain control for the first few postoperative days. The aim of this randomized clinical trial is to examine the effect of methadone (compared to hydromorphone) on postoperative pain management in patients undergoing major spine surgery

Detailed Description

Patients: 100 patients (ages 18-80) will be enrolled in this clinical trial. All patients presenting for elective posterior lumbar or thoracic spinal fusion surgery will be eligible for enrollment. Patients will be randomized to receive either methadone or hydromorphone on the basis of a computer generated random number table. Patients in each group will receive standard clinical intraoperative doses of either methadone (0.2 mg/kg) or hydromorphone (2 mg). An analysis of patients undergoing posterior lumbar fusion surgery at Evanston Hospital revealed that patients received, on average, approximately 2 mg of hydromorphone intraoperatively. The most commonly used doses of methadone administered in clinical studies have been either 0.2 mg/kg or a dose of 20 mg. Furthermore, these doses also represent dosages which appear to be approximately equipotent. Study medications will be prepared by the pharmacy, and all clinicians will be blinded to group assignment. Two syringes will be prepared for each patient, one which contains the study drug (either methadone 0.2 mg/kg or hydromorphone 2 mg), and the other containing the placebo (saline). If the patient is randomized to the methadone group, a 3 cc syringe containing 0.2 mg/kg of methadone and saline (total volume 3 cc) will be prepared, as well as a 10 cc syringe containing 10 cc of saline (placebo). If the patient is randomized to the hydromorphone group, a 3 cc syringe containing 3 cc of saline (placebo) will be prepared, as well as a 10 cc syringe containing 2 mg of hydromorphone with 9 cc of saline (total volume 10 cc). At induction of anesthesia, the 3 cc syringe containing either 0.2 mg/kg of methadone or placebo will be given over 5 seconds. At the conclusion of surgery, the 10 cc syringe of either hydromorphone or placebo will be titrated slowly per clinician's preference. The administration of all other anesthetic agents will be standardized and reflect the usual practices of anesthesiologists at Evanston Hospital (spine protocol).

Anesthesia will be standardized and include propofol for induction, a propofol and remifentanil infusion for maintenance (plus sevoflurane), and IV acetaminophen 1000 mg during the last 60 minutes of the case.

On arrival to the postanesthesia care unit (PACU), patients will be assessed for pain by PACU nurses per standard protocols. Patients will be evaluated for pain on PACU arrival and then every 15 minutes. Patients will be administered hydromorphone 0.25-0.5 mg for pain, and doses will be repeated until the patient is comfortable (pain < 3 on a scale of 0-10; 0=no pain and 10=worst pain imaginable). The patient will then be connected to a PCA device to deliver pain medication during the remainder of the postoperative period.

All postoperative management will be per standard surgical protocols

Sample Size: The primary end-point of the investigation is amount of hydromorphone used. In a clinical trial by Urban et al. of patients undergoing complex spine surgery using a standard anesthetic, average hydromorphone consumption in the first 24 hours was 27 mg (18). The investigators expect to see at least a 33% reduction in hydromorphone consumption in the methadone group. Group sample sizes of 39 and 39 achieve 91% power to detect a difference of 9.0 between the null hypothesis that both group means are 27.0 and the alternative hypothesis that the mean of group 2 is 18.0 with estimated group standard deviations of 10.0 and 10.0 and with a significance level (alpha) of 0.01000 using a two-sided two-sample t-test. The investigators plan to enroll a total of 100 patients to ensure complete collection of data.

Conditions

Hydromorphone Use; Acute Postoperative Pain; Patient Satisfaction; Chronic Persistent Surgical Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

methadone group

Patient will receive methadone 0.2 mg/kg at induction of anesthesia (single dose)

Group Type: EXPERIMENTAL

Methadone

Intervention Type: DRUG

Methadone 0.2 mg/kg administered at induction of anesthesia

Hydromorphone group

Patients will receive hydromorphone 2 mg at the end of the surgical procedure

Group Type: ACTIVE_COMPARATOR

Hydromorphone

Intervention Type: DRUG

Hydromorphone 2 mg administered at the conclusion of anesthesia

Interventions

Methadone

Methadone 0.2 mg/kg administered at induction of anesthesia

Intervention Type: DRUG

Hydromorphone

Hydromorphone 2 mg administered at the conclusion of anesthesia

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• All patients presenting for elective posterior lumbar or thoracic spinal fusion surgery will be eligible for enrollment.

Exclusion Criteria

1. Preoperative renal failure (defined as a serum creatinine > 2.0 mg/dL.)

2. American Society of Anesthesiologists Physical Status IV or V

3. Pulmonary disease necessitating home oxygen therapy

4. Allergy to methadone or hydromorphone

5. Preoperative recent history of opioid or alcohol abuse

6. Inability to use a PCA device or speak the English language

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Endeavor Health

OTHER

Sponsor Role: lead

Responsible Party

Glenn Murphy

Director, Clinical Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Glenn S Murphy, MD

Role: PRINCIPAL_INVESTIGATOR

Endeavor Health

Locations

NorthShore University HealthSystem

Evanston, Illinois, United States

Countries

United States

Other Identifiers

EH14-113

Identifier Type: -

Identifier Source: org_study_id