Use of Transdermal Clonidine in Trauma Patients

A Randomized Double Blinded Placebo Controlled Trial Of Transdermal Clonidine for Adjuvant Sedation in Ventilated Trauma Patients Experiencing Delirium

This study will attempt to learn how to better treat trauma patients with delirium who are on a breathing machine. Delirium, also known as acute, temporary brain dysfunction, is a common reason why ventilated patients can not be weaned from the breathing machine even though their lungs may be healthy enough to breathe without the machine. The study hopes to show that by decreasing the patient's delirium it will lead to quicker weaning from the breathing machine and possibly a quicker overall recovery as well. Patients enrolled in this study will be treated with Clonidine or placebo. Clonidine is a drug that produces significant calming effects, decreases anxiety, and reduces pain, but with a lower incidence of delirium than other medications used in the ICU for this purpose. Clonidine is not approved by the Federal Food and Drug Administration for treatment of delirium, but is commonly used for this purpose.

Study Overview

• Status: Terminated
• Conditions: Delirium
• Intervention / Treatment: Drug: Clonidine; Drug: Placebo

Detailed Description

Obtaining the appropriate level of sedation and analgesia in severely injured trauma patients admitted to the intensive care unit (ICU) can be challenging due to the diversity of injuries as well as the breadth of comorbidities present in this population. Clonidine may be a useful adjuvant to traditional analgesics such as opioids and sedatives such as benzodiazepines and propofol. Ventilator dependent trauma patients frequently fail extubation trials secondary to inappropriate sedation, inadequate analgesia or undertreated delirium. Patients that fail extubation for these reasons have a potentially preventable prolonged ventilator, ICU and hospital course. Ventilated trauma patients that meet criteria for our institution's SBT protocol and have the diagnosis of delirium will be considered for the trial if they have a documented failed SBT. We hypothesize treatment of this patient population with transdermal Clonidine will decrease delirium in trauma patients during their ICU stay. Patients enrolled in the treatment group will receive an oral loading dose of Clonidine 0.3 mg and placement of a Clonidine Transdermal system at a dose of 0.3-mg/day (Catapres TTS-3) covered by a patch overlay. In 12 hours the patient will receive a second and final dose of Clonidine 0.3 mg. The placebo group will receive a placebo oral tablet and the overlay patch only and in 12 hours they will receive a second and final placebo tablet. A total of 120 patients will be enrolled, 60 patients in each group. All patients will complete the study at end of Day 14 or upon discharge from the hospital, whichever comes sooner. Ventilator times will be measured in each group as well as the prevalence of delirium by the amount of positive CAM-ICU scores over the course of the trial.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ventilated male or female trauma patient 18 years of age or older admitted to the ICU >24 hours
2. Patient must meet minimal medical criteria for potential extubation (meet criteria for being placed on spontaneous breathing trials per established MUMC SBT protocol)
3. Patients must exhibit delirium as assessed by the CAM-ICU assessment tool
4. Patient must be declared stable from a neurologic, respiratory and cardiovascular standpoint to receive clonidine by the attending MD
5. Consent must be obtained prior to any study procedures

Exclusion Criteria:

1. Patient < 18 years old
2. Bradycardia (HR < 60)
3. Presence of active pacemaker
4. Hypotensive (<90/60)or active treatment of hypotension with vasoactive medications
5. Patient actively being treated with Clonidine or dexmedetomidine
6. Presence of allergy to Clonidine
7. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Transdermal Clonidine/Oral Clonidine; An oral loading dose of Clonidine 0.3 mg and placement of a Clonidine Transdermal system at a dose of 0.3 mg/day (Catapres TTS-3), with patch overlay, followed by a final dose of Clonidine 0.3 mg after 12 hours	Drug: Clonidine; An oral loading dose of Clonidine 0.3 mg and placement of Clonidine Transdermal system at a dose of 0.3-mg/day (Catapres TTS-3), with patch overlay, followed by a final dose of Clonidine 0.3mg after 12 hours
PLACEBO_COMPARATOR: Comparator; Placebo group will receive a placebo oral tablet and the overlay patch only and in 12 hours they will receive a second and final placebo tablet	Drug: Placebo; A placebo oral tablet and the overlay patch only and in 12 hours they will receive a second and final tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Mechanical Ventilation Following Administration of the First Dose of Clonidine or Placebo	data were not collected	2 or more years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Duration in Hours of Delirium Currently Used	As assessed by the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score Data were not collected	2 or more years
Time to Pass First SBT Following Administration of the First Dose of Clonidine or Placebo	Hours. data were not collected	2 or more years
Mean Incidence and Duration of Delirium	As assessed by daily CAM score currently used. data were not collected	2 or more years

Collaborators and Investigators

• Sponsor: Memorial Health University Medical Center

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: June 7, 2010
• First Submitted That Met QC Criteria: June 8, 2010
• First Posted (ESTIMATE): June 9, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: MHUMC-2010-04-02