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

• ClinicalTrials.gov Identifier: NCT00835159
• Recruitment Status: Completed
• First Posted: February 3, 2009
• Results First Posted: February 13, 2014
• Last Update Posted: February 9, 2015
• Sponsor: NYU Langone Health
• Collaborator: Novartis
• Information provided by (Responsible Party): NYU Langone Health

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Delirium; Postoperative Cognitive Dysfunction	Drug: Rivastigmine Patch; Other: Placebo Patch	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Rivastigmine in the Treatment of Postoperative Delirium: a Pilot Clinical Trial
• Study Start Date: December 2008
• Actual Primary Completion Date: July 2010
• Actual Study Completion Date: October 2010

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. Incidence of POD [ Time Frame: 72 hours postoperatively ]
   Is the incidence of POD not affected by rivastigmine treatment or not.

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• 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

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

NYU Langone Health

Novartis

Investigators

• Principal Investigator: Alex Bekker, MD, PhD; NYU School of Medicine

More Information

Publications of Results:

Zaslavsky A, Haile M, Kline R, Iospa A, Frempong-Boadu A, Bekker A. Rivastigmine in the treatment of postoperative delirium: a pilot clinical trial. Int J Geriatr Psychiatry. 2012 Sep;27(9):986-8. doi: 10.1002/gps.2801. No abstract available.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT00835159
• Other Study ID Numbers: H# 08-765
• First Posted: February 3, 2009
• Results First Posted: February 13, 2014
• Last Update Posted: February 9, 2015
• Last Verified: January 2015

Keywords provided by NYU Langone Health:

Postoperative Delirium; Postoperative Cognitive Dysfunction; Rivastigmine; Exelon; Memory impairment; Delirium; Cognitive function

Additional relevant MeSH terms:

Delirium; Emergence Delirium; Postoperative Cognitive Complications; Cognitive Dysfunction; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Postoperative Complications; Pathologic Processes; Rivastigmine; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuroprotective Agents; Protective Agents