Rivastigmine in the Treatment of Postoperative Delirium: a Pilot Clinical Trial

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00835159
First received: February 2, 2009
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to determine whether preoperative administration of Rivastigmine prevents the incidence of postoperative delirium in patients undergoing major surgery as well as postoperative cognitive dysfunction.


Condition Intervention Phase
Delirium
Postoperative Cognitive Dysfunction
Drug: Rivastigmine Patch
Other: Placebo Patch
Phase 4

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: Prevention
Official Title: Rivastigmine in the Treatment of Postoperative Delirium: a Pilot Clinical Trial

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Incidence of POD [ Time Frame: 72 hours postoperatively ] [ Designated as safety issue: No ]
    Is the incidence of POD not affected by rivastigmine treatment or not.


Enrollment: 30
Study Start Date: December 2008
Study Completion Date: October 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivastigmine Patch
Group receiving Rivastigmine Patch
Drug: Rivastigmine Patch
Rivastigmine Patch 4.6 mg/24 hours: 5 cm2 size containing 9 mg rivastigmine applied to upper back preoperatively for a period of 24 hours
Other Name: Exelon Patch
Placebo Comparator: Placebo Patch
A 2x2 gauze and a Tegaderm dressing applied to upper back within 3 hours of surgery for a period of 24 hours.
Other: Placebo Patch
A 2x2 gauze and a Tegaderm dressing applied to upper back within 3 hours of surgery for a period of 24 hours.

Detailed Description:

Postoperative delirium (POD) and Postoperative cognitive dysfunction (POCD) are common significant postoperative complications in elderly patients. A reduction of postoperative complications would lead to improved functional status, greater independence and reduction in health care cost. Scientific evidence shows that acetylcholinesterase inhibitors may reduce incidence and/or severity of postoperative delirium. We propose to conduct a randomized, double-masked, placebo-controlled study to assess effectiveness of Rivastigmine, an acetylcholinesterase inhibitor. Rivastigmine transdermal system (Exelon Patch) is approved by FDA for the treatment of mild to moderate Alzheimer's dementia and mild to moderate dementia associated with Parkinson's disease. Patients 65 y.o. and older undergoing major elective surgery will qualify for the study based on risk assessment guidelines. Patients screening will include Mini Mental Status Examination (MMSE to assess baseline cognitive function), Hamilton scale (to screen for depression), Telephone Interview of Cognitive Status Modified (TICS-M to assess baseline cognitive function over the phone) and Brief Test of Adult Cognition by Telephone (BTACT to assess baseline cognitive function over the phone). All study subjects will be randomly assigned to one of 2 groups prior to surgery. The treatment group will receive a Rivastigmine patch preoperatively covered by tegaderm dressing and a placebo group will receive just a tegaderm dressing. Both groups will be assessed twice daily at 9am and 4pm for up to 72 hours postoperatively with Confusion Assessment Method for Intensive Care Unit (CAM-ICU), Memorial Delirium Assessment Scale (MDAS) and Mini Mental Status Examination (to diagnose delirium and assess its severity). At one month and three months postoperatively subjects with a postoperative MMSE of 27 or less will be assessed for postoperative cognitive dysfunction. The assessment will be performed over the phone with TICS-M and Brief Test of Adult Cognition by Telephone. Outcomes will be divided into Primary and Secondary outcomes. Primary outcome will determine the proportions of patients with at least one episode of POD in the treatment and placebo groups, diagnosed by CAM-ICU. Secondary outcome will determine the proportions of patients with development of POCD in both groups, diagnosed by TICS-M at 1 month postoperatively. Secondary outcome will also determine cumulative number of POD episodes within first 3 days of hospital stay as diagnosed by CAM-ICU, severity of POD as diagnosed by the MDAS, recovery of cognitive function as diagnosed by MMSE, TICS-M and BTACT, and length of hospital stay.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

65 ≥ y.o. undergoing major elective surgery over 2 hours in length with one or more of the following:

  • Preoperative cognitive impairment
  • Age > 70 y.o.
  • Use of psychoactive medications
  • History of prior delirium
  • Severe illness/co-morbidity

Exclusion Criteria:

  • Delirium on admission Profound dementia No spoken/written English An emergent procedure Hypersensitivity to Rivastigmine
  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: NCT00835159

Locations
United States, New York
NYU Langone Medical Center, Department of Anesthesiology 550 First Avenue, RR-603
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Novartis
Investigators
Principal Investigator: Alex Bekker, MD, PhD NYU School of Medicine
  More Information

Publications:
Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00835159     History of Changes
Other Study ID Numbers: H# 08-765
Study First Received: February 2, 2009
Results First Received: April 12, 2013
Last Updated: February 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
Postoperative Delirium
Postoperative Cognitive Dysfunction
Rivastigmine
Exelon
Memory impairment
Delirium
Cognitive function

Additional relevant MeSH terms:
Delirium
Cognition Disorders
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Rivastigmine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 14, 2014