Pilot Study Comparing Treatment With Dexmedetomidine to Midazolam for Symptom Control in Advanced Cancer Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Fraser Health
Sponsor:
Information provided by (Responsible Party):
Fraser Health
ClinicalTrials.gov Identifier:
NCT01687751
First received: August 29, 2012
Last updated: January 8, 2013
Last verified: January 2013
  Purpose

Cancer patients with very difficult to control symptoms at the Abbotsford (AC) and Fraser Valley (FVC) Cancer Centers are referred and admitted to the Tertiary Palliative Care Units at the Abbotsford Regional Hospital and Cancer Center(ARHCC). For symptom management, patients are sometimes given midazolam continuously through a needle placed underneath the skin. While effective in symptom management, midazolam can be sedating, leaving patients unable to interact with loved ones in their last days.

This study is a pilot project. Before proceeding to a full-scale study, a "pilot study" or "feasibility study" is often carried out first to test the design of a study, the likelihood of successful recruitment or the acceptability of the intervention to potential subjects. The basic idea is to find out whether it will be practical to proceed to a larger study that will include more subjects. This type of study involves only a small number of subjects and therefore the results can only be used as a guide for further larger studies.

The investigators also will determine whether palliative care cancer patients taking a medication called dexmedetomidine would have improved rousability (more easily and fully awakened) and symptom control (pain, shortness of breath, nausea or confusion) compared with those taking standard of care which is receiving the medication midazolam. The use of dexmedetomidine in other clinical situations (in the Operating Room or Intensive Care Unit where the patient can still respond to the doctor) has been shown to be effective in symptom control and to provide a better degree of rousability to patients but has not been well studied in the palliative care environment.


Condition Intervention Phase
Pain Intractable
Delirium
Dyspnea
Nausea
Drug: Dexmedetomidine
Drug: Midazolam
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Dexmedetomidine Compared to Midazolam for Symptom Control in Advanced Cancer Patients: A Pilot Randomized Controlled Trial (RCT)

Resource links provided by NLM:


Further study details as provided by Fraser Health:

Primary Outcome Measures:
  • Number of subjects needed to recruit for a multicenter double blind randomized controlled phase III trial comparing dexmedetomidine to midazolam for symptom control in advanced cancer patients [ Time Frame: one year ] [ Designated as safety issue: No ]

    Sample size determination for significant improvement in:

    • Pain
    • Dyspnea
    • Nausea
    • Delirium
    • Rousability


Secondary Outcome Measures:
  • Change in pain (0 to 10 numerical scale) [ Time Frame: Up to 10 days ] [ Designated as safety issue: No ]
    Pain will be evaluated using the Edmonton Symptom Assessment Scale (ESASr)

  • Change in dyspnea (0 to 10 numerical scale) [ Time Frame: Up to 10 days ] [ Designated as safety issue: No ]
    Dyspnea will be evaluated using the Edmonton Symptom Assessment Scale (ESASr)

  • Change in nausea (0 to 10 numerical scale) [ Time Frame: Up to 10 days ] [ Designated as safety issue: No ]
    Nausea will be evaluated using the Edmonton Symptom Assessment Scale (ESASr)

  • Change in delirium (16 item clinician rated scale) [ Time Frame: Up to 10 days ] [ Designated as safety issue: No ]
    Delirium will be assessed using the Delirium Rating Scale-Revised-98 (DRS-R-98)

  • Rousability (10 point scale) [ Time Frame: Up to 10 days ] [ Designated as safety issue: No ]
    Rousability will be measured using the Richmond Agitation and Sedation Scale (RASS)

  • Acceptable symptom control (yes/no) [ Time Frame: Up to 10 days ] [ Designated as safety issue: No ]
    Acceptable symptom control of the difficult to control or intractable symptoms of pain, dyspnea, nausea or delirium will be assessed by a two part question addressed to each of subject, family member and assigned palliative care nurse. Subjective responses will be collected from each as binary variables (0/1) with two positive responses indicating acceptable symptom control overall.


Other Outcome Measures:
  • Time to enroll 20 subjects [ Time Frame: One year ] [ Designated as safety issue: No ]
    This information will be used to determine accrual rate. The accrual rate and the primary outcome measure of number needed to recruit will be used to determine the number of sites required for a multi-center double blind randomized controlled Phase III trial comparing dexmedetomidine to midazolam for symptom control in advanced cancer patients.

  • Cost determination for developing a budget for a large multi-center trial [ Time Frame: One year ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2012
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dexmedetomidine
Dexmedetomidine 0.2 to 1.1 mcg/kg/hr by continuous subcutaneous infusion for up to 10 days
Drug: Dexmedetomidine

Study drugs will be administered by continuous subcutaneous infusion using a weight based protocol at a rate between 1.0 to 5.5 mL/hr.

  • The study drug will be started at a rate of 1.0 mL/hr.
  • The infusion rate is incremented by 0.5 ml/hr every 30 minutes until acceptable symptom control, bradycardia (heart rate < 40) or hypotension (systolic blood pressure < 80) prevent further increase or maximum infusion rate of 5.5 ml/hr, whichever comes first. Achievement of acceptable symptom control will be defined, for purposes of this trial, as a consensus between reports from patient, family care giver and attending registered nurse
Other Names:
  • Precedex
  • DIN 02339366
Active Comparator: Midazolam
Midazolam 10 to 100 mcg/kg/hr by continuous subcutaneous infusion for up to 10 days
Drug: Midazolam

Study drugs will be administered by continuous subcutaneous infusion using a weight based protocol at a rate between 1.0 to 5.5 mL/hr.

  • The study drug will be started at a rate of 1.0 mL/hr.
  • The infusion rate is incremented by 0.5 ml/hr every 30 minutes until acceptable symptom control, bradycardia (heart rate < 40) or hypotension (systolic blood pressure < 80) prevent further increase or maximum infusion rate of 5.5 ml/hr, whichever comes first. Achievement of acceptable symptom control will be defined, for purposes of this trial, as a consensus between reports from patient, family care giver and attending registered nurse
Other Name: DIN 02240286

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater or equal to 19 years of age
  • Advanced cancer patient admitted to the Abbotsford Tertiary Palliative Care Unit
  • Difficult to control or intractable symptom (REF 38, page 3)
  • Midazolam CSCI would normally be considered for symptom management
  • Informed consent is able to be provided in the English language
  • Goals of care include do not resuscitate (DNR)
  • For intractable symptoms, patient would prefer proportional sedation rather than no sedation or total sedation.

Exclusion Criteria:

  • Second or third degree heart block (without pacemaker)
  • Uncompensated congestive heart failure
  • Heart rate less than 50 beats per minute
  • Mean arterial blood pressure (MAP) < 60
  • Weight below 35 kg. or above 85 kg.
  • Prior use within the preceding 14 days of high dose benzodiazepines equivalent to the use of 30 mg or more of midazolam or 6 mg or more of lorazepam per 24 hours.
  • Currently enrolled in any other research study involving drugs or devices
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01687751

Contacts
Contact: Neil K Hilliard, MD 604-851-4700 ext 642921 Neil.Hilliard@fraserhealth.ca

Locations
Canada, British Columbia
Abbotsford Regional Hospital and Cancer Center Recruiting
Abbotsford, British Columbia, Canada, V2S 0C2
Contact: Stuart Brown, MD    604-851-4798      
Contact: Neil K Hilliard, MD    604-851-4700 ext 642921      
Sponsors and Collaborators
Fraser Health
Investigators
Principal Investigator: Neil K Hilliard, MD 1. BC Cancer Agency 2. Fraser Health Authority
Principal Investigator: Stuart Brown, MD Fraser Health Authority
  More Information

Publications:

Responsible Party: Fraser Health
ClinicalTrials.gov Identifier: NCT01687751     History of Changes
Other Study ID Numbers: FHREB 2012-057
Study First Received: August 29, 2012
Last Updated: January 8, 2013
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by Fraser Health:
palliative care/
terminal care/
feasibility studies
conscious sedation/
dexmedetomidine/
midazolam/
infusions, subcutaneous/
terminally ill/
neoplasms/
treatment outcome
Precedex
"end of life"
Dying
Advanced cancer
mood/delirium/delirious

Additional relevant MeSH terms:
Delirium
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Midazolam
Dexmedetomidine
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on September 16, 2014