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Adjunct Methadone to Decrease the Duration of Mechanical Ventilation in the Medical Intensive Care Unit

Primary Purpose

Opioid Use, Unspecified With Withdrawal, Opioid-Induced Disorders, Delirium

Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Methadone
Placebo
Sponsored by
Henry Ford Health System
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid Use, Unspecified With Withdrawal focused on measuring Iatrogenic opioid abstinence syndrome, Methadone, Mechanical ventilation, ICU delirium, Continuous sedation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Mechanically ventilated patients with opioid consumption greater than or equal to 1,200 mcg of fentanyl or equivalent consumption of another opioid per day during the first 48 hours of intubation.

Exclusion Criteria:

  • Allergy to methadone
  • Admitted for head injury
  • Admitted for seizure
  • Seizure during admission, prior to enrollment
  • Subjects at high risk for developing a prolonged corrected QT (QTc) interval
  • Gastric residual volume ≥200 mL
  • Suspected obstruction or ileus
  • Nausea and vomiting
  • Recent abdominal surgery
  • Active upper or lower gastrointestinal bleeding
  • Active order for no medications by mouth or Total parenteral nutrition (TPN)
  • Pregnancy
  • Subjects receiving neuromuscular blocker infusions
  • Subjects taking antipsychotics at baseline

Sites / Locations

  • Henry Ford Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Methadone

Placebo

Arm Description

Methadone will be administered at a dose calculated from the subjects total daily opioid requirements, with a maximum methadone dose of 60 mg per day. The methadone will be administered every 8 hours as 5 mg capsules that will be given via an enteral feeding tube.

This will be a capsule containing only lactose and will be given every 8 hours via an enteral feeding tube. The number of placebo capsules will be calculated based on the subjects opioid requirements. This will ensure the same number of capsules will be given despite which arm the patient is enrolled in.

Outcomes

Primary Outcome Measures

Time to extubation
The time to extubation will be calculated and compared for both groups.

Secondary Outcome Measures

Cumulative opioid consumption
Cumulative doses of opioids will be collected and converted to morphine equivalents for analysis.
Level of sedation
Levels of pain and sedation will be assessed per institutional policy, which utilizes the Motor Agitation Assessment Scale (MAAS). Average daily scores will be collected and compared for each group.
Corrected QT interval
QTc intervals will be calculated and documented at baseline and every 24 hours after to ensure it does not become prolonged. These values will be compared between groups.
Cumulative Antipsychotic Use
The number of doses of antipsychotic medications will be collected and compared as a surrogate marker for presumed delirium.
Cumulative benzodiazepine consumption
Doses of all benzodiazepines will be collected and compared between groups to determine if methadone reduces consumption.

Full Information

First Posted
December 30, 2013
Last Updated
January 15, 2014
Sponsor
Henry Ford Health System
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1. Study Identification

Unique Protocol Identification Number
NCT02025855
Brief Title
Adjunct Methadone to Decrease the Duration of Mechanical Ventilation in the Medical Intensive Care Unit
Official Title
Adjunct Methadone to Decrease the Duration of Mechanical Ventilation in the Medical Intensive Care Unit
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Unknown status
Study Start Date
January 2014 (undefined)
Primary Completion Date
March 2015 (Anticipated)
Study Completion Date
March 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Henry Ford Health System

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine if administering methadone to mechanically ventilated patients in the medical intensive care unit (ICU) requiring continuous infusions of sedatives and analgesics will decrease the time of mechanical ventilation, when initiated within 48 hours of their admission. Patients meeting enrollment criteria will be randomly assigned to receive methadone or placebo in addition to standard care. Methadone is a long acting pain medication that is approved by the Food and Drug Administration (FDA) to manage withdrawal from opioids and moderate to severe pain. Both of these indications are a frequent concern for critically ill patients that require mechanical ventilation. These patients often require intravenous (IV) opioids to manage the pain they experience due to their illness, procedures, and mechanical ventilation. During this time patients can develop physical dependence, which leads to withdrawal symptoms when the opioids are stopped or the dose is reduced. These symptoms can include agitation, pain, diarrhea and several others. Currently this is managed by a slow reduction in the dose of the IV opioid, but this can lead to prolonged time on mechanical ventilation, which has been associated with increased morbidity. Administering oral methadone to patients experiencing withdrawal symptoms has been shown to reduce and even eliminate these symptoms in the outpatient setting. This should also benefit patients in the ICU experiencing withdrawal from intravenous opioids required during their stay. It may allow for the other opioids to be discontinued more quickly, allowing for a shorter duration of mechanical ventilation. The level of pain and sedation will be assessed between groups randomized to either methadone or placebo in addition to current intravenous sedative and analgesic agents. The duration of mechanical ventilation will be assessed between both groups. Opioid withdrawal symptoms may manifest or be mistaken for delirium symptoms. ICU delirium is often managed with antipsychotic medications. To assess if methadone can reduce the need for antipsychotic medication, all administered antipsychotic doses will be recorded and total consumption will be compared between the two groups. Methadone has been associated with abnormal heart rhythms in rare instances. To ensure patient safety, data from the heart monitor will be collected and compared between the two groups to assess for QT interval prolongation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Use, Unspecified With Withdrawal, Opioid-Induced Disorders, Delirium
Keywords
Iatrogenic opioid abstinence syndrome, Methadone, Mechanical ventilation, ICU delirium, Continuous sedation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Methadone
Arm Type
Experimental
Arm Description
Methadone will be administered at a dose calculated from the subjects total daily opioid requirements, with a maximum methadone dose of 60 mg per day. The methadone will be administered every 8 hours as 5 mg capsules that will be given via an enteral feeding tube.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
This will be a capsule containing only lactose and will be given every 8 hours via an enteral feeding tube. The number of placebo capsules will be calculated based on the subjects opioid requirements. This will ensure the same number of capsules will be given despite which arm the patient is enrolled in.
Intervention Type
Drug
Intervention Name(s)
Methadone
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Time to extubation
Description
The time to extubation will be calculated and compared for both groups.
Time Frame
Up to 14 days
Secondary Outcome Measure Information:
Title
Cumulative opioid consumption
Description
Cumulative doses of opioids will be collected and converted to morphine equivalents for analysis.
Time Frame
Up to 14 days
Title
Level of sedation
Description
Levels of pain and sedation will be assessed per institutional policy, which utilizes the Motor Agitation Assessment Scale (MAAS). Average daily scores will be collected and compared for each group.
Time Frame
Up to 14 days
Title
Corrected QT interval
Description
QTc intervals will be calculated and documented at baseline and every 24 hours after to ensure it does not become prolonged. These values will be compared between groups.
Time Frame
Up to 14 days
Title
Cumulative Antipsychotic Use
Description
The number of doses of antipsychotic medications will be collected and compared as a surrogate marker for presumed delirium.
Time Frame
Up to 14 days
Title
Cumulative benzodiazepine consumption
Description
Doses of all benzodiazepines will be collected and compared between groups to determine if methadone reduces consumption.
Time Frame
Up to 14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Mechanically ventilated patients with opioid consumption greater than or equal to 1,200 mcg of fentanyl or equivalent consumption of another opioid per day during the first 48 hours of intubation. Exclusion Criteria: Allergy to methadone Admitted for head injury Admitted for seizure Seizure during admission, prior to enrollment Subjects at high risk for developing a prolonged corrected QT (QTc) interval Gastric residual volume ≥200 mL Suspected obstruction or ileus Nausea and vomiting Recent abdominal surgery Active upper or lower gastrointestinal bleeding Active order for no medications by mouth or Total parenteral nutrition (TPN) Pregnancy Subjects receiving neuromuscular blocker infusions Subjects taking antipsychotics at baseline
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas L Smoot, PharmD
Organizational Affiliation
Henry Ford Health System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9726743
Citation
Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G. The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest. 1998 Aug;114(2):541-8. doi: 10.1378/chest.114.2.541.
Results Reference
background
PubMed Identifier
22420584
Citation
Wanzuita R, Poli-de-Figueiredo LF, Pfuetzenreiter F, Cavalcanti AB, Westphal GA. Replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial. Crit Care. 2012 Dec 12;16(2):R49. doi: 10.1186/cc11250.
Results Reference
background
PubMed Identifier
11765307
Citation
Lugo RA, MacLaren R, Cash J, Pribble CG, Vernon DD. Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU. Pharmacotherapy. 2001 Dec;21(12):1566-73. doi: 10.1592/phco.21.20.1566.34471.
Results Reference
background
PubMed Identifier
15781034
Citation
Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN. Impact of methadone treatment on cardiac repolarization and conduction in opioid users. Am J Cardiol. 2005 Apr 1;95(7):915-8. doi: 10.1016/j.amjcard.2004.11.055.
Results Reference
background
PubMed Identifier
1977561
Citation
Tobias JD, Schleien CL, Haun SE. Methadone as treatment for iatrogenic narcotic dependency in pediatric intensive care unit patients. Crit Care Med. 1990 Nov;18(11):1292-3. doi: 10.1097/00003246-199011000-00024. No abstract available.
Results Reference
background
PubMed Identifier
22392424
Citation
Johnson PN, Boyles KA, Miller JL. Selection of the initial methadone regimen for the management of iatrogenic opioid abstinence syndrome in critically ill children. Pharmacotherapy. 2012 Feb;32(2):148-57. doi: 10.1002/PHAR.1001. Epub 2012 Jan 24.
Results Reference
background
PubMed Identifier
21076361
Citation
Bowens CD, Thompson JA, Thompson MT, Breitzka RL, Thompson DG, Sheeran PW. A trial of methadone tapering schedules in pediatric intensive care unit patients exposed to prolonged sedative infusions. Pediatr Crit Care Med. 2011 Sep;12(5):504-11. doi: 10.1097/PCC.0b013e3181fe38f5.
Results Reference
background
PubMed Identifier
3612531
Citation
Hovav E, Weinstock M. Temporal factors influencing the development of acute tolerance to opiates. J Pharmacol Exp Ther. 1987 Jul;242(1):251-6.
Results Reference
background

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Adjunct Methadone to Decrease the Duration of Mechanical Ventilation in the Medical Intensive Care Unit

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