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 Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Conditions: Delirium; Postoperative Cognitive Dysfunction
• Interventions: Drug: Rivastigmine Patch; Other: Placebo Patch
• Enrollment: 30

Participant Flow

Recruitment Details	Patientsof 65years and older admitted for elective surgery undergeneral anesthesia were screened. Only patients at risk fordeveloping POD were considered for recruitment
Pre-assignment Details	This was a randomized, placebo controlled, double-blind clinical trial. Screened patients were 65 years +, having elective surgery under general anesthesia. Only patients at risk for POD were considered for recruitment. Eligible patients received rivastigmine 5cm2 transdermal or placebo patch. 30 patients recruited but only 28 had complete data.

Arm/Group Title	Rivastigmine 5-cm2 Transdermal Patch	Placebo Patch
Arm/Group Description	Only patients at risk for developing POD were considered for recruitment. That risk was based on the presence of at least one of five predictive factors: (1) preoperative cognitive impairment (Mini mental state examination (MMSE)<24); (2) advanced age (>70 years); (3) preoperative use of psychoactive drugs; (4) history of prior delirium; and/or (5) severe illness or comorbidity. Eligible patients received a rivastigmine 5-cm2 transdermal patch	Only patients at risk for developing POD were considered for recruitment. That risk was based on the presence of at least one of five predictive factors: (1) preoperative cognitive impairment (Mini mental state examination (MMSE)<24); (2) advanced age (>70 years); (3) preoperative use of psychoactive drugs; (4) history of prior delirium; and/or (5) severe illness or comorbidity. Eligible patients received a placebo patch.
Period Title: Overall Study
Started	11	17
Completed	11	17
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Rivastigmine 5-cm2 Transdermal Patch	Placebo Patch	Total
Arm/Group Description		Only patients at risk for developing POD were considered for recruitment. That risk was based on the presence of at least one of five predictive factors: (1) preoperative cognitive impairment (Mini mental state examination (MMSE)<24); (2) advanced age (>70 years); (3) preoperative use of psychoactive drugs; (4) history of prior delirium; and/or (5) severe illness or comorbidity. Eligible patients received a rivastigmine 5-cm2 transdermal patch	Only patients at risk for developing POD were considered for recruitment. That risk was based on the presence of at least one of five predictive factors: (1) preoperative cognitive impairment (Mini mental state examination (MMSE)<24); (2) advanced age (>70 years); (3) preoperative use of psychoactive drugs; (4) history of prior delirium; and/or (5) severe illness or comorbidity. Eligible patients received a placebo patch.	Total of all reporting groups
Overall Number of Baseline Participants		11	17	28
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants	17 participants	28 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	11 100.0%	17 100.0%	28 100.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	11 participants	17 participants	28 participants
		72.0909 (5.55796)	72.6471 (6.52822)	72.4286 (6.06403)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants	17 participants	28 participants
	Female	6 54.5%	10 58.8%	16 57.1%
	Male	5 45.5%	7 41.2%	12 42.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	11 participants	17 participants	28 participants
		11	17	28

Outcome Measures

1. Primary Outcome

Title	Incidence of POD
Description	Is the incidence of POD not affected by rivastigmine treatment or not.
Time Frame	72 hours postoperatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rivastigmine Patch	Placebo Patch
Arm/Group Description:	Eligible patients received a rivastigmine 5-cm2 transdermal patch	Eligible patients received a placebo patch
Overall Number of Participants Analyzed	11	17
Measure Type: Number; Unit of Measure: participants
	2	4

Adverse Events

Time Frame	No adverse events related to the use of a rivastigmine transdermal patch were determined in this clinical trial.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Rivastigmine 5-cm2 Transdermal Patch	Placebo Patch
Arm/Group Description	Only patients at risk for developing POD were considered for recruitment. That risk was based on the presence of at least one of five predictive factors: (1) preoperative cognitive impairment (Mini mental state examination (MMSE)<24); (2) advanced age (>70 years); (3) preoperative use of psychoactive drugs; (4) history of prior delirium; and/or (5) severe illness or comorbidity. Eligible patients received a rivastigmine 5-cm2 transdermal patch	Only patients at risk for developing POD were considered for recruitment. That risk was based on the presence of at least one of five predictive factors: (1) preoperative cognitive impairment (Mini mental state examination (MMSE)<24); (2) advanced age (>70 years); (3) preoperative use of psychoactive drugs; (4) history of prior delirium; and/or (5) severe illness or comorbidity. Eligible patients received a placebo patch.
All-Cause Mortality
	Rivastigmine 5-cm2 Transdermal Patch	Placebo Patch
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Rivastigmine 5-cm2 Transdermal Patch	Placebo Patch
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/11 (0.00%)	0/17 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Rivastigmine 5-cm2 Transdermal Patch	Placebo Patch
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/11 (0.00%)	0/17 (0.00%)

Limitations and Caveats

The study was halted prematurely because of a warning letter issued by the rivastigmine manufacturer indicating the possibility of increased mortality associated with the oral administration of the drug in critically ill patients.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: ALEXANDER ZASLAVSKY
• Organization: NYU Langone Medical Center
• Phone: 212-263-5569
• EMail: michael.haile@nyumc.org

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 Submitted: February 2, 2009
• First Posted: February 3, 2009
• Results First Submitted: April 12, 2013
• Results First Posted: February 13, 2014
• Last Update Posted: February 9, 2015