Clinical trial NCT02025855: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Opioid Use, Unspecified With Withdrawal
Opioid-Induced Disorders
Delirium
Keywords: Iatrogenic opioid abstinence syndrome
Methadone
Mechanical ventilation
ICU delirium
Continuous sedation
Lead sponsor: Henry Ford Health System
Sponsor class: OTHER
First posted: 2014-01-01
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Time to extubation
timeFrame: Up to 14 days
Secondary outcomes:
measure: Cumulative opioid consumption
timeFrame: Up to 14 days
measure: Level of sedation
timeFrame: Up to 14 days
measure: Corrected QT interval
timeFrame: Up to 14 days
measure: Cumulative Antipsychotic Use
timeFrame: Up to 14 days
measure: Cumulative benzodiazepine consumption
timeFrame: Up to 14 days
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
Study officials:
affiliation: Henry Ford Health System
name: Thomas L Smoot, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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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.
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.
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