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

Tracking Information

• First Submitted Date: February 2, 2009
• First Posted Date: February 3, 2009
• Results First Submitted Date: April 12, 2013
• Results First Posted Date: February 13, 2014
• Last Update Posted Date: February 9, 2015
• Study Start Date: December 2008
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 12, 2014)

Incidence of POD [ Time Frame: 72 hours postoperatively ]

Is the incidence of POD not affected by rivastigmine treatment or not.

• Original Primary Outcome Measures (submitted: February 2, 2009): Development of postoperative delirium within 72 hours postoperatively diagnosed by CAM-ICU [ Time Frame: 72 hours postoperatively ]
• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: February 2, 2009)

• To determine total number of postoperative delirium episodes for each patient [ Time Frame: 72 hours postoperatively ]
• To determine severity of postoperative delirium as diagnosed by the Memorial Delirium Assessment Scale [ Time Frame: 72 hours postoperatively ]
• To determine length of hospital stay [ Time Frame: measures hospital stay ]
• To assess cognitive function by Telephone Interview Cognitive Status and Brief Test of Adult Cognition by Telephone tests at 1 month and 3 months postoperatively. [ Time Frame: one month and three months postoperatively ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Rivastigmine in the Treatment of Postoperative Delirium: a Pilot Clinical Trial
• Official Title: Rivastigmine in the Treatment of Postoperative Delirium: a Pilot Clinical Trial
• 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.
• 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Delirium
• Postoperative Cognitive Dysfunction

Intervention

• 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
• 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.

Study Arms

• Experimental: Rivastigmine Patch
  Group receiving Rivastigmine Patch
  Intervention: Drug: Rivastigmine 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.
  Intervention: Other: Placebo Patch

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 5, 2010): 30
• Original Estimated Enrollment (submitted: February 2, 2009): 180
• Actual Study Completion Date: October 2010
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 65 Years and older (Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00835159
• Other Study ID Numbers: H# 08-765
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: NYU Langone Health
• Original Responsible Party: Alex Bekker, MD, PhD, Professor of Anesthesiology and Neurosurgery, Vice Chair for Research at NYU School of Medicine, New York University School of Medicine Department of Anesthesiology
• Current Study Sponsor: NYU Langone Health
• Original Study Sponsor: Same as current
• Collaborators: Novartis

Investigators

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

• PRS Account: NYU Langone Health
• Verification Date: January 2015