Preoperative Oral Methadone for Patients Undergoing Cardiac Surgery: Reduction of Postoperative Pain

Pain Clinical Trial

Official title:

Preoperative Oral Methadone for Patients Undergoing Cardiac Surgery: Reduction of Postoperative Pain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02774499
• Other study ID #: Bio16-02
• Status: Completed
• Phase: Phase 2
• First received: April 6, 2016
• Last updated: December 28, 2017
• Start date: April 2016
• Est. completion date: December 2017

Study information

• Verified date: December 2017
• Source: University of Saskatchewan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Oral medications like gabapentin and acetaminophen are commonly given to patients prior to surgery to provide balanced anaesthesia. Intravenous methadone has been shown to decrease postoperative pain as well as postoperative nausea and vomiting, which are known barriers to discharge. Oral methadone would be a convenient alternative to give as a preoperative medication with its bioavailability approaching 80%. No clinical trials to date have explored the utility of oral methadone as a preoperative analgesic to improve postoperative outcomes. Current literature shows preoperative IV methadone reduces opioid consumption in the perioperative period for cardiac surgeries; therefore, investigators hypothesize that preoperative oral methadone will also reduce postoperative pain and opioid consumption in patients undergoing sternotomy for cardiac surgery.

Description:

Investigators propose a prospective, randomized, double-blind, placebo-controlled trial to investigate the effects of preoperative oral methadone on postoperative pain. The trial will be conducted in compliance with the protocol, Good Clinical Practice (GCP), and University of Saskatchewan Research Ethics Committee principles using an intent-to-treat model. The primary endpoint will be postoperative pain in the ICU, and secondary outcomes will include morphine requirements as measured by Patient Controlled Analgesia (PCA). Secondary endpoints include opioid consumption at 15 minutes and at 2, 4, 8, 12, 24, 48, and 72 hours post extubation. Other secondary endpoints include the following: pain with cough (using a 0-10 verbal pain scale) measured at the time of extubation then daily until post-op day three. Secondary outcomes that will be recorded from nursing assessment records include: incidence of nausea and/or vomiting requiring antiemetics, pruritus, hypoventilation (respiratory rate less than 8 breaths/min), hypoxemia (oxygen saturation less than 90%), time to extubation, and sedation (Richmond Agitation-Sedation Scale of -4 or -5).

Patients will receive a dose of either oral methadone or placebo prior to entering the operating room. The dose given will be 0.3 mg/kg (to a maximum of 30 mg) or equivalent volume of placebo. An blinded research assistant will receive an envelope the morning of surgery outlining if the patient is in group A or B as well as their weight in kg. For the methadone arm the research assistant will prepare the appropriate amount of methadone, which is dispensed as 10 mg/mL, and dilute it to a total volume of 5 mL in sugary syrup to mask its taste. For the placebo arm a similar volume will be mixed at a 0.3 mg/kg volume and diluted to a total volume of 5 mL of sugary syrup. The methadone or placebo will be given to the researcher in a syringe. The researcher will give syringe to the patient and the patient will administer the solution to themself orally prior to entering the operating room.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: December 2017
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• presenting for elective first-time CABG cardiac surgery with anticipated extubation within 12 hours

Exclusion Criteria:

• < 18 years of age

• preoperative renal failure requiring dialysis or serum creatinine greater than 176 µmol/L

• significant hepatic dysfunction (liver function tests more than twice the upper limit of normal)

• ejection fraction less than 30%

• corrected QT interval (QTc) on ECG > 440ms for men and 450ms for women

• pulmonary disease necessitating home oxygen therapy

• preoperative requirement for inotropic agents or intra-aortic balloon pump to maintain hemodynamic stability

• emergency surgery

• allergy to methadone

• use of preoperative opioids or recent history of opioid abuse

Related Conditions & MeSH terms

• Pain
• Pain, Postoperative

Intervention

Drug:
• Methadone
0.3mg/kg of methadone given preoperatively (to maximum of 30mg)
• Placebo
equivalent volume (5mL) of syrup given preoperatively

Locations

Country	Name	City	State
Canada	Saskatoon Health Region, 410 22nd Street East	Saskatoon	Saskatchewan

Sponsors (1)

Lead Sponsor	Collaborator
University of Saskatchewan

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain score (VRS)	Pain score as measured by 0-10 Verbal Rating Score (VRS)	24 hours
Secondary	Total Morphine Consumption (mg)	Total dose in mg of IV morphine administered via Patient Controlled Analgesia	72 hours
Secondary	Pain score (VRS)	Pain score as measured by 0-10 Verbal Rating Score (VRS)	Up to 72 hours postoperative
Secondary	Time to extubation	Time from start of surgery until removal of endotracheal tube in ICU	up to 24 hours postoperative
Secondary	Level of sedation	Level of sedation as measured by the Richmond Agitation-Sedation Scale (RASS) in ICU	up to 72 hours postoperative
Secondary	Incidence of opioid-related side effects	Incidence of as nausea, vomiting, pruritus, hypoventilation, and hypoxia during a seventy-two hour monitoring period	up to 72 hours postoperative