Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Methadone Versus Morphine for Orthopedic Surgery Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00892606
Recruitment Status : Completed
First Posted : May 4, 2009
Results First Posted : May 17, 2017
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
University of Louisville

Tracking Information
First Submitted Date  ICMJE April 30, 2009
First Posted Date  ICMJE May 4, 2009
Results First Submitted Date  ICMJE April 6, 2017
Results First Posted Date  ICMJE May 17, 2017
Last Update Posted Date June 14, 2017
Study Start Date  ICMJE January 2009
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 6, 2017)
Opioid Consumption During the 48 Hours After Surgery [ Time Frame: 48 hours ]
The amount of opioid required for postoperative pain relief
Original Primary Outcome Measures  ICMJE
 (submitted: May 1, 2009)
Opioid Consumption During the 48 Hours After Surgery [ Time Frame: 48 hours ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
  • Number of Participants With Post Operative Nausea and Vomiting [ Time Frame: 48 hours ]
    rates subjects experienced PONV
  • Visual Pain Score [ Time Frame: 48 hours ]
    Patients rated their pain with the numerical VPS from 0 to 10, with 10 being the worst pain possible and 0 being no pain
Original Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2009)
  • Time to initial dose of rescue analgesic [ Time Frame: 48 hours ]
  • Overall rescue analgesic [ Time Frame: 48 hours ]
  • Side effects with special attention paid to respiratory rate and possible respiratory depression, and PONV [ Time Frame: 48 hours ]
  • Overall satisfaction of the patient with the analgesic graded on a scale of 1-5 [ Time Frame: 48 hours ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Methadone Versus Morphine for Orthopedic Surgery Patients
Official Title  ICMJE Effectiveness of Pre-Operative Methadone Versus Morphine for Post-Operative Analgesia in Orthopedic Surgery Patients
Brief Summary The investigators propose to compare analgesia by methadone and ketamine with a combination of morphine and ketamine in orthopedic surgery patients with moderate to severe pain. The investigators hypothesize that when given with ketamine before surgical incision, methadone is more effective than morphine in reducing postoperative morphine consumption and reducing pain during movement.
Detailed Description

Patients will receive 1-4 mg midazolam before being transferred to the operating room. All patients will receive standard ASA monitoring. In the operating room, the anesthesiologist will open a randomization envelope to determine patient group assignment (see below). Patients will be anesthetized with 0.2 mg/kg ketamine, 2 µg/kg fentanyl and propofol or etomidate IV. Muscle relaxant of the anesthesiologist's choice will be given and the patient will be intubated. After intubation, the computer-generated randomization codes stored in opaque envelopes will be opened. The patients will be randomized to one of two groups:

  1. Methadone group: Patients will receive 0.2 mg/kg of methadone IV immediately after intubation
  2. Control group: Patients will receive 0.2 mg/kg of morphine IV immediately after intubation

The unblinded investigator will draw the drug and dilute to a total volume of 10 cc. This syringe will be handed to the anesthesia provider, who will administer the medication after induction. They will be maintained with oxygen, air and an inhalational agent of anesthesiologist's choice, targeted at BIS between 40 and 60. Additional analgesia will be provided with fentanyl in 50 µg increments as required throughout surgery. At the end of surgery the neuromuscular block will be reversed and patients will breathe spontaneously. Fentanyl will be titrated to maintain a respiratory rate of 12-15 breaths per minute to obtain an O2 saturation > 95% and the other extubation criteria are met before tracheal extubation . The intraoperative use of narcotics, sedatives and anesthetic drugs will be noted. The type of surgery, the duration of surgery and use of additional analgesics and antiemetics will be noted.

An investigator blinded to randomization will track the patients in the PACU. If rescue medication is necessary, morphine IV will be given in 2-4 mg increments up to a total of 20 mg. If the patients continue to report pain (VAS > 4), IV hydromorphone will be given in 0.5 mg dose every 10-15 minutes until the patient has adequate analgesia (VAS < 4), as decided by the PACU nurse.

Patients will receive morphine patient-controlled analgesia (PCA) for pain relief as the primary analgesic. Percocet (Acetaminophen/Oxycodone 325 mg/5 mg) or Lortab (Acetaminophen/Hydrocodone 325/5 mg) will be prescribed as needed to maintain VRS < 4.

In the PACU, vital signs including respiratory rate, heart rate, non-invasive blood pressure, sedation score and oxygen saturation will be recorded every 15 minutes. VAS scores for pain will be obtained from the patient every 15 minutes until the patient is discharged to the floor. VAS (visual analog scale) is a 100-mm scale where 0 = no pain and 100 = worst pain imaginable. The investigator will record sedation scores every 15 minutes using the following scale until patient is discharged to the floor:

0-Patient is fully alert

  1. Patient has intermittent sedation
  2. Patient sedated but responsive to verbal stimuli
  3. Patient unresponsive to verbal stimuli

Patients will be seen at 8 am and 4 pm on the following day and will be contacted at home or in the hospital on POD 2 and 3 for information regarding pain scores and analgesic requirement. The initial dose of rescue analgesic and time it is given will be recorded. VAS at rest and on movement will be recorded, when the patients are seen or VRS will be recorded via phone contact. Morphine or other analgesics required during the first 24 and 48 hours after surgery, and times to first ambulation, first fluid, solid and flatus will be recorded, as will incidence and severity of postoperative nausea and vomiting be recorded.

Our primary outcome will be opioid consumption during the 48 hours after surgery. All analgesics consumed will be converted to morphine equivalent.

The secondary outcomes will be

  1. Overall rescue analgesic, converted into equipotent doses compared between the two groups
  2. Side effects with special attention paid to respiratory rate and possible respiratory depression, and PONV
  3. Visual pain score at 48 h post-op.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Fracture
  • Pain, Postoperative
Intervention  ICMJE
  • Drug: Methadone
    Patients will receive 0.2 mg/kg of methadone IV immediately after intubation
    Other Names:
    • Symoron
    • Dolophine
    • Amidone
    • Methadose
    • Physeptone
    • Heptadon
    • 6-(Dimethylamino)-4,4-diphenylheptan-3-one (IUPAC name)
  • Drug: Morphine
    Patients will receive 0.2 mg/kg of morphine IV immediately after intubation
    Other Names:
    • Opiate
    • (5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol
Study Arms  ICMJE
  • Experimental: Methadone
    Patients received 2 µg/kg fentanyl, 0.2 mg/kg ketamine and 0.2 mg/kg of methadone IV with induction of general anesthesia.
    Intervention: Drug: Methadone
  • Active Comparator: Control
    Patients received 2 µg/kg fentanyl, 0.2 mg/kg ketamine, and 0.2 mg/kg morphine (standard of care)
    Intervention: Drug: Morphine
Publications * Wadhwa A, Clarke D, Goodchild CS, Young D. Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery. Anesth Analg. 2001 Feb;92(2):448-54.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 6, 2017)
75
Original Estimated Enrollment  ICMJE
 (submitted: May 1, 2009)
80
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ASA I-III
  • Ages 18-65 years
  • Presenting for lower extremity orthopedic surgery involving fracture of long bones at University of Louisville Hospital
  • Surgery expected to last more than one hour
  • Patient expected to have moderate to severe post-operative pain
  • Patient refused regional anesthesia or has a contraindication to regional anesthesia

Exclusion Criteria:

  • Any known contraindications to methadone including hypothyroidism, Addison's disease, prostatic hypertrophy, or urethral stricture.
  • Difficulty or inability to understand the study or protocol
  • Known renal or hepatic dysfunction
  • BMI> 35
  • Known respiratory or cardiovascular problems, such as obstructive sleep apnea or oxygen saturation of less than 92% on room air
  • Taking any of the known drugs that induce or inhibit the cytochrome p450 enzyme systems. Common examples of these drugs are antifungal, antiretroviral, barbiturates, dexamethasone, and macrolide antibiotics.
  • Pregnancy
  • Taking preoperative opioids for more than 2 weeks before the surgery
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00892606
Other Study ID Numbers  ICMJE UofL IRB # 08.0200
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Louisville
Study Sponsor  ICMJE University of Louisville
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anupama Wadhwa, MD University of Louisville
PRS Account University of Louisville
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP