Clinical trial NCT03908060: Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Laparoscopic Hysterectomy
Official title: Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Laparoscopic Hysterectomy: a Prospective, Double-blind, Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Postoperative Pain
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2019-04-09
Enrollment: 126
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: TREATMENT

Brief summary: The role of a single-dose of intraoperative methadone on postoperative pain and opioid consumption in patients undergoing hysterectomy remains scarcely explored. A prospective double-blind, randomised controlled trial investigating the effect of a single-dose of intraoperative methadone in patients scheduled for same day hysterectomy is therefore conducted.

Detailed description: Background with aim: Hysterectomy is the most common major gynaecological procedure in the world and hysterectomy on benign indications are increasingly being performed as same-day surgery. Therefore, perioperative anaesthesia has moved towards the use of very short-acting opioids with the incitement to speed up extubation and facilitate hospital discharge. However, the potential consequence is that more patients experience pain and discomfort.

Methadone has several desirable pharmacological features, and a single intraoperative dose of the long acting opioid could therefore theoretically expand the analgesic window and reduce postoperative opioid consumption compared to the more conventional use of short-acting opioids. The aim of this study is to investigate the effect of a single-dose of intravenous intraoperative methadone on postoperative opioid consumption, pain and side effects in patients scheduled for hysterectomy for benign indications. Our primary hypothesis is that intravenous perioperative methadone reduces opioid consumption (oral cumulative equivalent dose) by 30% during the first 24 postoperative hours compared to intravenous morphine.

Methods: 126 patients will be included in an investigator-initiated, prospective, randomised, double-blind, controlled trial with two arms: an intervention arm (methadone 0.2 mg/kg ideal body weight) and a control arm (morphine 0.2 mg/kg ideal body weight). The study will be GCP-monitored, and is approved by the Danish Health and Medicines Authority (2018-004351-20) and the Central Denmark Region Committees on Health Research Ethics (1-10-72-365-18).

Hypothesis: The results will probably be applicable to other types of surgery involving visceral pain, and thus the present study has the potential to improve the pain management for a large number of patients undergoing surgery.

Eligibility criteria: Inclusion Criteria:

- Patients scheduled for elective laparoscopic hysterectomy for benign indications

Exclusion Criteria:

* American Society of Anaesthesiologists (ASA) physical status IV or V
* prolonged QT-interval assessed by electrocardiogram (\> 440 milliseconds)
* Existing treatment with medications prolonging the QT-interval
* Hysterectomy due to malignancy or acute bleeding disorders
* Allergy to study drugs
* Preoperative daily use of opioids
* Severe respiratory insufficiency
* Heart failure
* Acute alcohol intoxication/delirium tremens
* Increased intracranial pressure
* Acute liver disease
* Acute abdominal pain
* Liver insufficiency
* Kidney insufficiency
* Treatment with rifampicin
* Breastfeeding
* Inability to provide informed consent.

Primary outcomes:
measure: Opioid consumption at 24 hours after extubation (cumulative opioid consumption)
timeFrame: 24 hours
measure: Opioid consumption at 6 hours after extubation (cumulative opioid consumption)
timeFrame: 6 hours
Secondary outcomes:
measure: Pain intensity (NRS, 0-10) at rest and coughing
timeFrame: 0-48 hours after extubation
measure: Postoperative side effects/ adverse events (nausea and vomiting, sedation, hypoventilation, and hypoxemia)
timeFrame: 0-72 hours after extubation
Other outcomes:
Locations:
city: Horsens
country: Denmark
facility: Department of Anaesthesiology and Intensive Care, Horsens Regional Hospital
state: Central Denmark Region
Study officials:
affiliation: Department of Anaesthesiology and Intensive Care, Horsens Regional Hospital
name: Kristian Friesgaard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Shear T, Parikh KN, Patel SS, Gupta DK. Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. Anesthesiology. 2015 May;122(5):1112-22. doi: 10.1097/ALN.0000000000000633.
citation: Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Deshur MA, Vender JS, Benson J, Newmark RL. Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial. Anesthesiology. 2017 May;126(5):822-833. doi: 10.1097/ALN.0000000000001609.
citation: Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
citation: Richlin DM, Reuben SS. Postoperative pain control with methadone following lower abdominal surgery. J Clin Anesth. 1991 Mar-Apr;3(2):112-6. doi: 10.1016/0952-8180(91)90007-a.
citation: Chui PT, Gin T. A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Anaesth Intensive Care. 1992 Feb;20(1):46-51. doi: 10.1177/0310057X9202000109.