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

NCT ID: NCT00835159

Last Updated: 2015-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2010-10-31

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.

Conditions

Delirium; Postoperative Cognitive Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Rivastigmine Patch

Group receiving Rivastigmine Patch

Group Type: EXPERIMENTAL

Rivastigmine Patch

Intervention Type: DRUG

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

Placebo Patch

A 2x2 gauze and a Tegaderm dressing applied to upper back within 3 hours of surgery for a period of 24 hours.

Group Type: PLACEBO_COMPARATOR

Placebo Patch

Intervention Type: OTHER

A 2x2 gauze and a Tegaderm dressing applied to upper back within 3 hours of surgery for a period of 24 hours.

Interventions

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

Intervention Type: DRUG

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 Type: OTHER

Other Intervention Names

Exelon Patch

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

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alex Bekker, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

NYU School of Medicine

Locations

NYU Langone Medical Center, Department of Anesthesiology 550 First Avenue, RR-603

New York, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 22886871 (View on PubMed)

Other Identifiers

H# 08-765

Identifier Type: -

Identifier Source: org_study_id