Impact of Methadone on Prolonged Mechanical Ventilation in Patients on Continuous Treatment With Opioids

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effect of methadone on the duration on mechanical ventilation in critically ill patients receiving more than 72 hours of mechanical ventilation (MV) by comparing the number of ventilator free days from enrollment to the time of discharge, to assess the safety of methadone administration in critically ill patients while in the hospital and to determine hospital length of stay from the time of enrollment to the time of discharge

Official Title
-----------------
Impact of Methadone on Prolonged Mechanical Ventilation in Patients on Continuous Treatment With Opioids, a Randomized Trial (IMPACTOR Study)

Conditions
-----------------
Effect of Methadone on the Duration on Mechanical Ventilation

Intervention / Treatment
-----------------
* Drug: Methadone group
* Drug: Usual care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients on Intermittent mandatory ventilation (IMV) for more than 72 hours Patients infused Fentanyl or Hydromorphone for more than 72 hours Patients with evidence of reversal of process that caused respiratory failure, adequate oxygenation (PaO2/fraction of inspired oxygen (FiO2)>200; Positive end expiratory pressure (PEEP)≤8 and Ph≥7.2 Patients hemodynamically stable Patients with a failed single or multiple attempts at spontaneous breathing trials Exclusion Criteria: Patients with history of opioid drug abuse Patients receiving schedule II narcotics on a chronic basis for longer than 6 months prior to ICU admission or on other analgesic infusions other than Fentanyl or Hydromorphone Patients with cervical spinal cord injury or neuromuscular disease Patients with end stage liver disease at ICU admission (ie, International normalized ratio ≥2and not taking warfarin and/or a total serum bilirubin ≥1.5 times above normal limits Patients with prolonged QTc interval ≥500 Patients with prior history of cardiac conduction defects or sudden death Patients with QTc increase of ≥60 milliseconds above the value of prior EKGs measured during current ICU admission Patients with more than 5 days on IV analgesia Patients intubated for more than 3 days Patients without feeding tubes Patients not receiving enteral feeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methadone group<br> | Drug: Methadone group<br>* Participants will be started on Methadone 5mg, 10mg or 15mg every 8 hours depending on Fentanyl drip rate (0-100mcg/hr, 100-200mcg/hr or >200mcg/hr) or hydromorphone drip rate (0-1.5mg/hr, 1.5-3mg/hr, or >3mg/hr).<br>|
| Active Comparator: Non-Methadone group<br> | Drug: Usual care<br>* Participants will receive usual care with IV Fentanyl or hydromorphone per hospital protocols<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants on methadone that get extubated |  | from day of intubation to day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants that develop prolonged corrected QT interval (QTC) after administration of methadone |  | from first day patient given Methadone to date patient discharged or transferred from hospital( upto about 7 days after admission ) | 
| ICU length of stay |  | at time of discharge from ICU( upto about 3 days after admission ) | 
| ICU mortality |  | end of ICU stay ( upto about 3 days after admission ) | 
| hospital length |  | at time of discharge from hospital ( upto about 7 days after admission ) | 
| hospital mortality. |  | end of hospital stay ( upto about 7 days after admission ) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
opioids, mechanical ventilation