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

Delirium Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02025855
• Other study ID #: Smoot_8503
• Status: Enrolling by invitation
• Phase: Phase 4
• First received: December 30, 2013
• Last updated: January 15, 2014
• Start date: January 2014
• Est. completion date: March 2015

Study information

• Verified date: January 2014
• Source: Henry Ford Health System
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 46
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Methadone

• Placebo

Locations

Country	Name	City	State
United States	Henry Ford Hospital	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Henry Ford Health System

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to extubation	The time to extubation will be calculated and compared for both groups.	Up to 14 days	No
Secondary	Cumulative opioid consumption	Cumulative doses of opioids will be collected and converted to morphine equivalents for analysis.	Up to 14 days	No
Secondary	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.	Up to 14 days	No
Secondary	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.	Up to 14 days	Yes
Secondary	Cumulative Antipsychotic Use	The number of doses of antipsychotic medications will be collected and compared as a surrogate marker for presumed delirium.	Up to 14 days	No
Secondary	Cumulative benzodiazepine consumption	Doses of all benzodiazepines will be collected and compared between groups to determine if methadone reduces consumption.	Up to 14 days	No