Trial Outcomes & Findings for Methadone vs. Fentanyl Administration on Postoperative Pain Control in Pediatric Patients Undergoing Cardiac Surgery (NCT NCT02747875)

Last Updated: 2021-06-01

Results Overview

The distribution of the total opioid dose in the first 24 hours will be evaluated by randomization group (methadone vs. fentanyl) and differences between groups will be tested. It is hypothesized that compared to fentanyl, methadone administered intraoperative will result in a significantly lower total opioid dose (morphine or oxycodone) during the first 24 hour postoperative period. Assuming no difference between the two treatment strategies in the population, a total sample size of 52 in each group will provide 80% power to detect an effect size of 0.1. Significance will be measured as a 30% reduction in postoperative pain requirement.

Recruitment status

TERMINATED

Study phase

Target enrollment

26 participants

Primary outcome timeframe

24 hours

Results posted on

2021-06-01

Participant Flow

The trial was terminated because enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results. Additionally, without notice formulations of the study drug methadone became unavailable and remain unavailable due to production shortages.

Participant milestones

Participant milestones
Measure	Control - Fentanyl Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Fentanyl: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.	Treatment - Methadone Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Methadone: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.
Overall Study STARTED	12	14
Overall Study COMPLETED	11	13
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Control - Fentanyl Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Fentanyl: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.	Treatment - Methadone Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Methadone: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.
Overall Study Physician Decision	1	0
Overall Study Adverse Event	0	1

Baseline Characteristics

Methadone vs. Fentanyl Administration on Postoperative Pain Control in Pediatric Patients Undergoing Cardiac Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control - Fentanyl n=12 Participants Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Fentanyl: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.	Treatment - Methadone n=14 Participants Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Methadone: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.	Total n=26 Participants Total of all reporting groups
Age, Categorical <=18 years	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	4.1 years n=5 Participants	4.4 years n=7 Participants	4.2 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	14 participants n=7 Participants	26 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: The trail was terminated because enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results. Additionally, without notice formulations of the study drug methadone became unavailable and remain unavailable due to production shortages. Therefore, no analysis was performed on the data.

Outcome measures

Outcome measures
Measure	Control - Fentanyl n=11 Participants Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Fentanyl: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.	Treatment - Methadone n=13 Participants Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Methadone: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.
Total Opioid Dose, in Morphine Equivalents, in the First 24 Hours After Pediatric Cardiac Bypass Surgery.	0.55 mg postop morphine equivelant 24hr Standard Deviation 0.21	0.48 mg postop morphine equivelant 24hr Standard Deviation 0.24

SECONDARY outcome

Timeframe: 24 hours

Opioid-related adverse events will be monitored closely and a secondary analysis will compare the incidence of side effects between the two groups during the first 24-hour postoperative period. The Pearson's contingency chi-square test will be used to evaluate any differences between the randomization groups in opioid-related adverse events during the first 24-hour postoperative period.

Outcome measures

Outcome measures
Measure	Control - Fentanyl n=11 Participants Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Fentanyl: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.	Treatment - Methadone n=13 Participants Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Methadone: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.
Opioid-related Adverse Events Including: Respiratory Failure, Cardiovascular Instability, and Postoperative Nausea and Vomiting Ondansetron Doses	3.81 events Standard Deviation 1.70	3.43 events Standard Deviation 2.47
Opioid-related Adverse Events Including: Respiratory Failure, Cardiovascular Instability, and Postoperative Nausea and Vomiting Emesis Episodes	2.72 events Standard Deviation 2.45	2.08 events Standard Deviation 1.90
Opioid-related Adverse Events Including: Respiratory Failure, Cardiovascular Instability, and Postoperative Nausea and Vomiting Hypoventilation Episodes	0 events Standard Deviation 0	0 events Standard Deviation 0
Opioid-related Adverse Events Including: Respiratory Failure, Cardiovascular Instability, and Postoperative Nausea and Vomiting Arrhythmias	0 events Standard Deviation 0	0 events Standard Deviation 0

Adverse Events

Control - Fentanyl

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Treatment - Methadone

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Control - Fentanyl n=12 participants at risk Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Fentanyl: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.	Treatment - Methadone n=14 participants at risk Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. The medication will be prepared as described and all research and staff personnel as well as the study participant will be blinded to treatment group assignment. Methadone: The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Under the direction of the cardiac anesthesiologist subjects will be premedicated and general anesthesia will be induced with standard anesthetic monitoring and management. Participants will receive 0.3 mg/kg of methadone prior to surgical incision, over 20 minutes. General anesthesia will be maintained with inhalational anesthetics and paralytics. The subject will continue to be evaluated for hemodynamic stability, bleeding, and respiratory effort. The postoperative intensive care phase will begin at time of room admission and end at day three of hospital stay. All subjects will receive morphine or oxycodone analgesics and sedation medication based on the hospital's postoperative pain control and agitation protocol. Standard electronic documentation will be maintained throughout and include: medications, vital signs, and events.
Surgical and medical procedures Postoperative Bleeding	0.00% 0/12 • 2 weeks	7.1% 1/14 • Number of events 1 • 2 weeks

Other adverse events

Adverse event data not reported

Additional Information

Dr. Andrew Waberski, Assistant Professor

Children's National Hospital

Phone: 2024762025

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place