Clinical trial NCT04475029: Methadone in Cystectomy Patients
Official title: Clinical Effectiveness and Safety of Intraoperative Methadone in Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain, Postoperative
Postoperative Complications
Pathologic Processes
Bladder Cancer
Pain
Signs and Symptoms
Neurologic Manifestations
Neurologic Symptoms
Side Effect of Drug
Keywords: morphine
methadone
analgesics
opioids
effect of drugs
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2020-07-17
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial.
Primary purpose: TREATMENT

Brief summary: The role of a single-dose intraoperative methadone on postoperative pain and opioid consumption in patients undergoing Surgeon Accuracy Robot Assistant cystectomy. A prospective double-blind, randomized controlled trial investigating the effect of a single-dose of intraoperative methadone in patients undergoing robotassisted cystectomy.

Detailed description: During early recovery after surgery, intravenous opioids are typically administered to control the pain, either as intermittent bolus administration by nursing staff or by a patient-controlled analgesia device. Unfortunately, repeated doses or boluses of shorter-acting opioids, such as morphine, oxycodone and fentanyl, result in fluctuating blood concentrations, with the inherent risk of only relatively brief periods of adequate pain relief. Moreover, the use of shorter-acting opioids increases the risk of opioid-associated side effects, such as sedation, nausea and vomiting. An alternative approach to the postoperative use of shorter-acting opioids is therefore called for.

In this respect, methadone is an opioid with unique pharmalogical properties that may be advantageous when applied intraoperatively. A single-dose of this long acting opioid could provide a stable analgesia and potentially reduce the need for shorter-acting opioids

Method:

110 patients will be included in an investigator-initiated, prospective, randomised, double-blind, controlled trial with two arms: intervention arm (methadone 0.15 mg/kg ideal body weight). Control arm (morphine 0.15 mg/kg ideal body weight). The study will be GCP-monitored, and is approved by the Danish Health and Medicines Authority (2020041652) and the Central Denmark Region Committees on Health Research Ethics (1-10-72-275-19).

Hypothesis We hypothesize that a single-dose of intravenous intraoperative methadone is efficient and safe for the treatment of postoperative pain after cystectomy.

Objectives The primary objective is to determine whether a single-dose of intravenous methadone reduces postoperative opioid consumption when compared to morphine. The secondary objectives are to compare the effect and safety of intravenous methadone and morphine on postoperative pain, side effects, patient satisfaction and length of stay.

Eligibility criteria: Inclusion Criteria:

- All patients (≥18 years) scheduled for elective robot assisted cystectomy.

Exclusion Criteria:

* American Society of Anesthesiologists (ASA) physical status IV or V
* Prolonged QTc-interval assessed by electrocardiogram (\> 440 milliseconds)
* Existing treatment with a high risk of QTc-interval prolongation
* Allergy to study drugs
* Preoperative daily use of opioids
* Inability to provide informed consent
* Severe respiratory insufficiency (oxygen treatment at home)
* Heart failure (ejection fraction \< 30%)
* Acute abdominal pain
* Signs of severe liver dysfunction (cirrhosis, inflammation/hepatitis or liver malignancy)
* Severe kidney insufficiency (estimated Glomerular Filtration Rate \< 30 ml/min)
* Treatment with rifampicin
* Phaeochromocytoma
* Treatment with MAO-inhibitor during the last 14 days
* Pregnancy
* Nursing mothers
* Intraoperative conversion to open surgery (secondary inclusion criterion)
* Epidural analgesia in relation to surgical procedure

Primary outcomes:
measure: Opioid consumption (morphine mg equivalents)
timeFrame: 3 hours
measure: Opioid consumption (morphine mg equivalents)
timeFrame: 24 hours
Secondary outcomes:
measure: Pain intensity
timeFrame: within 24 hours
measure: Opioid consumption (morphine mg equivalents)
timeFrame: 72 hours
measure: PONV
timeFrame: Within 24 hours
measure: Level of sedation
timeFrame: 3 hours
measure: Adverse events
timeFrame: 6 hours
measure: Patient satisfaction from 0-10.
timeFrame: 24 hours
measure: Discharge
timeFrame: 6 days
Other outcomes:
measure: Pain intensity
timeFrame: 32-72 hours
measure: PONV
timeFrame: 32-72 hours
measure: Gastrointestinal function
timeFrame: 6-72 hours
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
References: