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

May 6, 2021 updated by: Andrew Waberski

The Effect of Methadone vs. Fentanyl Administration on Postoperative Pain Control in Pediatric Patients Undergoing Cardiac Surgery: A Randomized, Double-Blinded Controlled Trial

The purpose of this study is to determine if methadone improves postoperative pain control in pediatric patient's undergoing cardiac surgery.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The proposed study will be conducted at Children's National Health System (CNHS). Pediatric subjects undergoing cardiac surgery requiring cardiopulmonary bypass will be recruited. Eligible and consenting participants will be assigned a unique identification number and will be randomly assigned to receive either methadone or fentanyl using a computer-generated randomization scheme. A total of 52 participants will be enrolled to each arm of the study, providing 80% power to detect a 30% difference between groups.

Once informed consent is obtained the inpatient pharmacist at CNHS will randomly assign eligible participants to receive methadone or fentanyl. The pharmacist will prepare 0.3 mcg/kg of methadone and 20 mcg/kg of fentanyl for loading dose administration, diluted to 10 mL.

The IDS pharmacy will store and maintain all medications per Department of Pharmacy standard operating procedures for waste of a controlled substance (C-II) drug.

The treatment phase will begin at the induction of general anesthesia and finish at the end of the surgical procedure. Standard anesthetic practice for monitoring, induction, and maintenance of general anesthesia will be preserved throughout.

Participants will receive either 0.3 mg/kg of methadone or 20 mcg/kg of fentanyl prior to surgical incision, over 20 minutes. The medication will be prepared as described above and all research and staff personnel as well as the study participant will be blinded to treatment group assignment.

As per standard anesthetic practice, the subject will continue to be evaluated for hemodynamic stability, postoperative risk of bleeding, and respiratory effort. Morphine at 0.05 mg/kg per dose will be administered intravenously as needed for pain control. Surgical procedures and times will be recorded in the operative report via the electronic medical record.

Postoperative ICU Phase The postoperative cardiac intensive care unit phase will begin at admission to the Cardiac Intensive Care Unit (CICU) and will end on the third day of hospital admission. Postoperative care including hemodynamic stability, resuscitation, and respiratory support will be at the discretion of the CICU team.

As per CICU protocol, the nurse will monitor and record vital signs and pain scale (FLACC) scores beginning at handoff from the anesthesia team to the intensive care team. The nurse will continue to document vital signs including: blood pressure, heart rate, respiratory rate, oxygen saturation, temperature, minute ventilation when mechanically ventilated, and oxygen supplementation when appropriate, in the electronic medical record every hour. As per nursing protocol, FLACC scores will be recorded in the electronic medical record every 4 hours or when the nursing staff witnesses pain during the entirety of the subject's CICU stay.

All subjects will receive analgesics and sedation medication based on CICU postoperative pain control and agitation protocol

Data Collection The investigator or designee, blinded to group assignment, will collect all of the relevant data from the electronic medical record within six months of the cardiac surgery and enter it into the Medical Center's proprietary web-based data-entry and data-management system, REDcap (Research Electronic Data Capture). The source of information will be medical records at the Children's National Health System "Anesthesiology" and "Bear Tracks" information systems provided by Cerner Corporation.

Data will be obtained specifically for research purposes. Subject identifiers (e.g. name, date of birth, address) will not be entered into the REDcap system. The previously assigned unique identification numbers will be used.

Statistical Considerations Significance will be measured as a 30% reduction in postoperative pain requirement. Statistical analysis will be used to evaluate any differences between the randomization groups in opioid-related adverse events during the first 24-hour postoperative period.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 7 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age greater than or equal to 2 years and less than 8 years at the time of randomization.
  2. Weight greater than 6 kg.
  3. American Society of Anesthesiologists (ASA) physical status of ASA I, II, or III (Appendix I).
  4. Informed consent to participate from the parent or legally authorized guardian.
  5. Scheduled for congenital cardiac bypass surgery.

Exclusion Criteria

Subjects will not be eligible to participate in the study if any of the following exclusion criteria apply:

  1. History or a family (parent or sibling) history of malignant hyperthermia.
  2. Known significant hepatic disorders determined by medical history, medical record documentation, physical examination, or laboratory tests obtained during the routine preoperative cardiac surgery evaluation or cardiology visit (International Normalized Ratio (INR)>1.5).
  3. Emergency Cardiac Surgery.
  4. History of chronic nausea and/or vomiting.
  5. Currently receiving inotropic agents or using a pacemaker.
  6. Prexisting long QTc interval of greater than 460ms determined by medical history, medical record documentation, or electrocardiogram obtained during the routine preoperative cardiac surgery evaluation.
  7. History of documented pulmonary hypertension, respiratory dysfunction, or requirement of supplemental oxygen therapy.
  8. History of opioid abuse, addiction, or tolerance.
  9. Obesity defined as a body weight greater than 130% of the ideal weight.
  10. Participation in another clinical trial or any study that may interfere with participation in this trial.
  11. History of allergic reaction to methadone or fentanyl.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: 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.
Other Names:
  • Sublimaze
Active Comparator: 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.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Opioid Dose, in Morphine Equivalents, in the First 24 Hours After Pediatric Cardiac Bypass Surgery.
Time Frame: 24 hours
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.
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Opioid-related Adverse Events Including: Respiratory Failure, Cardiovascular Instability, and Postoperative Nausea and Vomiting
Time Frame: 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.
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Andrew Waberski

Investigators

  • Principal Investigator: Andrew T Waberski, MD, Children's National Health System

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Actual)

February 7, 2019

Study Completion (Actual)

February 7, 2019

Study Registration Dates

First Submitted

April 13, 2016

First Submitted That Met QC Criteria

April 21, 2016

First Posted (Estimate)

April 22, 2016

Study Record Updates

Last Update Posted (Actual)

June 1, 2021

Last Update Submitted That Met QC Criteria

May 6, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7364

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Study Data/Documents

  1. Study Protocol
    Information identifier: Pr 7364
    Information comments: The Effect of Methadone vs. Fentanyl Administration on Postoperative Pain Control in Pediatric Patients Undergoing Cardiac Surgery. A Randomized, Double-Blinded Controlled Trial

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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