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

This study has been withdrawn prior to enrollment.
(Study design determined to be not likely feasible)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01687751
First Posted: September 19, 2012
Last Update Posted: May 25, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Fraser Health
  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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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 ]

    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 ]
    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 ]
    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 ]
    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 ]
    Delirium will be assessed using the Delirium Rating Scale-Revised-98 (DRS-R-98)

  • Rousability (10 point scale) [ Time Frame: Up to 10 days ]
    Rousability will be measured using the Richmond Agitation and Sedation Scale (RASS)

  • Acceptable symptom control (yes/no) [ Time Frame: Up to 10 days ]
    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 ]
    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 ]

Enrollment: 0
Study Start Date: November 2012
Study Completion Date: November 2014
Primary Completion Date: November 2014 (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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01687751


Locations
Canada, British Columbia
Abbotsford Regional Hospital and Cancer Center
Abbotsford, British Columbia, Canada, V2S 0C2
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:
Abernethy AP. Pain and palliative care pharmacotherapy literature summaries and analyses. J Pain Palliat Care Pharmacother. 2008;22(2):145-51.
Anger KE, Szumita PM, Baroletti SA, Labreche MJ, Fanikos J. Evaluation of dexmedetomidine versus propofol-based sedation therapy in mechanically ventilated cardiac surgery patients at a tertiary academic medical center. Crit Pathw Cardiol. 2010 Dec;9(4):221-6. doi: 10.1097/HPC.0b013e3181f4ec4a.
Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg. 2004 Jan;98(1):153-8, table of contents.
Brinkkemper T, van Norel AM, Szadek KM, Loer SA, Zuurmond WW, Perez RS. The use of observational scales to monitor symptom control and depth of sedation in patients requiring palliative sedation: a systematic review. Palliat Med. 2013 Jan;27(1):54-67. doi: 10.1177/0269216311425421. Epub 2011 Nov 1. Review.
Caraceni A, Simonetti F. Palliating delirium in patients with cancer. Lancet Oncol. 2009 Feb;10(2):164-72. doi: 10.1016/S1470-2045(09)70018-X. Review.
Chang VT, Hwang SS, Feuerman M. Validation of the Edmonton Symptom Assessment Scale. Cancer. 2000 May 1;88(9):2164-71.
Cheung CW, Ying CL, Chiu WK, Wong GT, Ng KF, Irwin MG. A comparison of dexmedetomidine and midazolam for sedation in third molar surgery. Anaesthesia. 2007 Nov;62(11):1132-8.
Chrysostomou C, Schmitt CG. Dexmedetomidine: sedation, analgesia and beyond. Expert Opin Drug Metab Toxicol. 2008 May;4(5):619-27. doi: 10.1517/17425255.4.5.619 . Review.
Clark, S., & Ezra, M. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients. Journal of the Intensive Care Society, 12(3), 244-245, 2011.
Coull JT, Jones ME, Egan TD, Frith CD, Maze M. Attentional effects of noradrenaline vary with arousal level: selective activation of thalamic pulvinar in humans. Neuroimage. 2004 May;22(1):315-22.
Coyne PJ, Wozencraft CP, Roberts SB, Bobb B, Smith TJ. Dexmedetomidine: exploring its potential role and dosing guideline for its use in intractable pain in the palliative care setting. J Pain Palliat Care Pharmacother. 2010 Dec;24(4):384-6. doi: 10.3109/15360288.2010.518227.
Dere K, Sucullu I, Budak ET, Yeyen S, Filiz AI, Ozkan S, Dagli G. A comparison of dexmedetomidine versus midazolam for sedation, pain and hemodynamic control, during colonoscopy under conscious sedation. Eur J Anaesthesiol. 2010 Jul;27(7):648-52. doi: 10.1097/EJA.0b013e3283347bfe.
Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003 Jun 11;289(22):2983-91.
Gerlach AT, Murphy CV, Dasta JF. An updated focused review of dexmedetomidine in adults. Ann Pharmacother. 2009 Dec;43(12):2064-74. doi: 10.1345/aph.1M310. Review.
Guinter JR, Kristeller JL. Prolonged infusions of dexmedetomidine in critically ill patients. Am J Health Syst Pharm. 2010 Aug;67(15):1246-53. doi: 10.2146/ajhp090300. Review.
Jackson KC 3rd, Wohlt P, Fine PG. Dexmedetomidine: a novel analgesic with palliative medicine potential. J Pain Palliat Care Pharmacother. 2006;20(2):23-7. Review.
Jones GM, Murphy CV, Gerlach AT, Goodman EM, Pell LJ. High-dose dexmedetomidine for sedation in the intensive care unit: an evaluation of clinical efficacy and safety. Ann Pharmacother. 2011 Jun;45(6):740-7. doi: 10.1345/aph.1P726. Epub 2011 Jun 10.
Kehl KA. Treatment of terminal restlessness: a review of the evidence. J Pain Palliat Care Pharmacother. 2004;18(1):5-30. Review.
Kent CD, Kaufman BS, Lowy J. Dexmedetomidine facilitates the withdrawal of ventilatory support in palliative care. Anesthesiology. 2005 Aug;103(2):439-41.
Kunisawa T. Dexmedetomidine hydrochloride as a long-term sedative. Ther Clin Risk Manag. 2011;7:291-9. doi: 10.2147/TCRM.S14581. Epub 2011 Jul 11.
Lum, K. L., & Sanders, H. G. A comparison of midazolam and flunitrazepam in end-of-life care. Progress in Palliative Care, 19(1), 1-6, 2011.
Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009 May-Jun;50(3):206-17. doi: 10.1176/appi.psy.50.3.206.
Maze M, Angst MS. Dexmedetomidine and opioid interactions: defining the role of dexmedetomidine for intensive care unit sedation. Anesthesiology. 2004 Nov;101(5):1059-61.
Mercadante S, Intravaia G, Villari P, Ferrera P, David F, Casuccio A. Controlled sedation for refractory symptoms in dying patients. J Pain Symptom Manage. 2009 May;37(5):771-9. doi: 10.1016/j.jpainsymman.2008.04.020. Epub 2008 Nov 28.
Muttu S, Liu EH, Ang SB, Chew PT, Lee TL, Ti LK. Comparison of dexmedetomidine and midazolam sedation for cataract surgery under topical anesthesia. J Cataract Refract Surg. 2005 Sep;31(9):1845-6.
Prommer E. Review article: dexmedetomidine: does it have potential in palliative medicine? Am J Hosp Palliat Care. 2011 Jun;28(4):276-83. doi: 10.1177/1049909110389804. Epub 2010 Dec 3. Review.
Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009 Feb 4;301(5):489-99. doi: 10.1001/jama.2009.56. Epub 2009 Feb 2.
Roberts SB, Wozencraft CP, Coyne PJ, Smith TJ. Dexmedetomidine as an adjuvant analgesic for intractable cancer pain. J Palliat Med. 2011 Mar;14(3):371-3. doi: 10.1089/jpm.2010.0235. Epub 2011 Jan 17.
Ruokonen E, Parviainen I, Jakob SM, Nunes S, Kaukonen M, Shepherd ST, Sarapohja T, Bratty JR, Takala J; "Dexmedetomidine for Continuous Sedation" Investigators. Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation. Intensive Care Med. 2009 Feb;35(2):282-90. doi: 10.1007/s00134-008-1296-0. Epub 2008 Sep 16.
Shehabi, Y., Botha, J. A., Ernest, D., Freebairn, R. C., Reade, M., Roberts, B. L., et al. Clinical application, the use of dexmedetomidine in intensive care sedation. Critical Care and Shock, 13(2), 40-50, 2010.
Soares LG, Naylor C, Martins MA, Peixoto G. Dexmedetomidine: a new option for intractable distress in the dying. J Pain Symptom Manage. 2002 Jul;24(1):6-8.
Tan JA, Ho KM. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med. 2010 Jun;36(6):926-39. doi: 10.1007/s00134-010-1877-6. Epub 2010 Apr 8. Review.
Tobias JD. Subcutaneous dexmedetomidine infusions to treat or prevent drug withdrawal in infants and children. J Opioid Manag. 2008 Jul-Aug;4(4):187-91.
Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci. 2001 Spring;13(2):229-42. Erratum in: J Neuropsychiatry Clin Neurosci 2001 Summer;13(3):433.
Ustün Y, Gündüz M, Erdoğan O, Benlidayi ME. Dexmedetomidine versus midazolam in outpatient third molar surgery. J Oral Maxillofac Surg. 2006 Sep;64(9):1353-8.
Wallace S, Mecklenburg B, Hanling S. Profound reduction in sedation and analgesic requirements using extended dexmedetomidine infusions in a patient with an open abdomen. Mil Med. 2009 Nov;174(11):1228-30.
Fraser Health Authority (FHA) Hospice Palliative Care Program Symptom Guideline "Refractory Symptoms and Palliative Sedation Therapy Guideline", May 9, 2011. Retrieved from http://www.fraserhealth.ca/media/RefractorySymptomsandPalliativeSedationTherapyRevised_Sept%2009.pdf )
Flanagan E, Gentry J. He's taking how much Dilaudid! Dexmedetomidine: a novel approach to refractory symptom management. Presentation of the American Academy of Hospice and Palliative Medicine & Hospice and Palliative Nurses Association Conference 2011 Feb 16-19; Vancouver, British Columbia
Doyle, D. et al, Oxford Textbook of Palliative Medicine, Third Edition 2004, p. 219.
Storey P, Knight C. Assessment and Treatment of Pain in the Terminally Ill. UNIPAC Three, Hospice/Palliative Care Training for Physicians, A Self-Study Program, American Academy of Hospice and Palliative Medicine, Second Edition, Mary Ann Liebert, Inc., 2003, p. 62.

Responsible Party: Fraser Health
ClinicalTrials.gov Identifier: NCT01687751     History of Changes
Other Study ID Numbers: FHREB 2012-057
First Submitted: August 29, 2012
First Posted: September 19, 2012
Last Update Posted: May 25, 2015
Last Verified: January 2013

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

Additional relevant MeSH terms:
Delirium
Dyspnea
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Dexmedetomidine
Midazolam
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents


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