ACTION

CompletedPhase 4Results posted

Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer's Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44

A 24 Week, Prospective, Randomized, Parallel-group, Double-blind, Multi-center Study (ENA713DUS44) Comparing the Effects of Rivastigmine Patch 15 cm^2 vs. Rivastigmine Patch 5 cm^2 on ACTivities of Daily Living and CognitION in Patients With Severe Dementia of the Alzheimer's Type (ACTION) and a 24-week Open-label Extension to Study ENA713DUS44

Lead sponsor

Novartis

Asset

Rivastigmine

Listed sites

Recruiting sites

Enrollment

716

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 3-12•Study partner/caregiver required

Primary endpoints

•ADCS-Activities of Daily Living (ADCS-ADL)•The Severity Impairment Battery (SIB) Score

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDCENA713DUS44

NCT IDNCT00948766

Timeline

Milestones

Study start2009-07 (month precision)

Study first posted2009-07-29estimated

Primary completion2012-01actual (month precision)

Study completion2012-06actual (month precision)

Results first posted2013-02-11estimated

Last update posted2013-08-28estimated

Assets

Drug assets

Rivastigmine

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

Core study

Inclusion Criteria:

•Diagnosis of probable Alzheimer's disease (AD) according to National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria.

•A Mini-Mental State Examination (MMSE) score of ≥ 3 and ≤ 12.

•Be able to complete at least 1 item on the Severe Impairment Battery (SIB).

•Residing with someone in the community or in regular contact with the primary caregiver.

•Be ambulatory or ambulatory with aid

Exclusion criteria

•An advanced, severe, progressive, or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient at special risk.

•Patients currently residing in a nursing home.

•Any current medical or neurological condition other than AD that could explain the patient's dementia.

•A current diagnosis of probable or possible vascular dementia.

•A current diagnosis of severe or unstable cardiovascular disease.

•A current diagnosis of bradycardia (< 50 beats per minute [bpm]), sick-sinus syndrome, or conduction defects.

•Clinically significant urinary obstruction.

•History of malignancy of any organ system within the past 5 years unless patient is verified to be in stable condition with no active metastasis.

•Current diagnosis of an active skin lesion/disorder that would prevent the patient from using a transdermal patch every day.

•A known exaggerated pharmacological sensitivity or hypersensitivity to drugs similar to rivastigmine, or to other cholinergic compounds.

•Taken any of the following substances (at the time of the Baseline Visit [Visit 2]).

•Succinylcholine-type muscle relaxants during the previous 2 weeks.

•Lithium during the previous 2 weeks.

•An investigational drug during the previous 4 weeks.

•A drug or treatment known to cause major organ system toxicity during the previous 4 weeks.

•Rivastigmine (oral or transdermal patch), donepezil, galantamine, other cholinesterase inhibitors (eg, tacrine, physostigmine, or pyridostigmine), or other approved treatments for Alzheimer's disease during the previous 2 weeks, with exception of stable treatment with memantine for at least 3 months before study entry (Visit 1).

•Centrally acting anticholinergic drugs including tricyclic and tetracyclic antidepressants during the previous 4 weeks.

•Selegiline unless taken at a stable dose during the previous 4 weeks.

•Peripheral anticholinergics not taken at a stable dose during the previous 4 weeks.

Extension study

Inclusion Criteria:

•Complete the double-blind phase (Week 24) of the core study.

•Provide, if mentally competent, a separate written informed consent prior to participation in the extension study. In addition, the patient's caregiver, will provide written informed consent prior to the patient's participation in the open-label extension study. If the patient is not able to provide written informed consent, written informed consent must be obtained from the legally authorized representative on the patient's behalf.

•Continue to reside with someone in the community or in regular contact with the primary caregiver; patients who reside in an assisted living facility are eligible to participate.

•Continue to have a primary caregiver willing to accept responsibility for supervising treatment (eg, application and removal of the patch daily at approximately the same time of day), assessing the condition of the patient throughout the extension study.

•Must be medically stable and tolerating the current dose of rivastigmine patch as determined by the investigator.

Exclusion Criteria:

Refer to the core study protocol for full details of the exclusion criteria.

•Patients who discontinued the core study due to any reason are excluded.

•No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Endpoints (14)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Behavior / neuropsychiatric

Global cognition

Function / daily living

Global cognition

4 endpoints

Primary/protocol endpoint

Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the core study

change from baseline, improvement

Primary/registry result

Core Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the core study

change from baseline, improvement

Posted result

Group	Value (mean), Units on a scale	Standard deviation
Rivastigmine 13.3 mg/24 h Transdermal Patchn=313 Participants	-1.6	13.54
Rivastigmine 4.6 mg/24 h Transdermal Patchn=316 Participants	-6.4	14.01

Secondary/protocol endpoint

Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the extension study

change from baseline, improvement

Secondary/registry result

Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the extension study

change from baseline, improvement

Posted result

Group	Value (mean), Units on a scale	Standard deviation
Rivastigmine 13.3 mg/24 h Transdermal Patchn=379 Participants	-5.9	16.72

Function / daily living

4 endpoints

Primary/protocol endpoint

Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the core study

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Primary/registry result

Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the core study

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (mean), Units on a scale	Standard deviation
Rivastigmine 13.3 mg/24 h Transdermal Patchn=310 Participants	-2.6	6.82
Rivastigmine 4.6 mg/24 h Transdermal Patchn=303 Participants	-3.6	7.68

Secondary/protocol endpoint

Extension Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the extension study

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Extension Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the extension study

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (mean), Units on a scale	Standard deviation
Rivastigmine 13.3 mg/24 h Transdermal Patchn=372 Participants	-4.3	8.37

Behavior / neuropsychiatric

6 endpoints

Secondary/protocol endpoint

Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the core study

threshold achievement, improvement

Secondary/protocol endpoint

Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the core study

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the extension study

threshold achievement, improvement

Secondary/registry result

Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the core study

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of patients	Reported bounds
Rivastigmine 13.3 mg/24 h Transdermal PatchMarked improvementn=313 Participants	1.0	-
Moderate improvementn=313 Participants	3.5	-
Minimal improvementn=313 Participants	20.1	-
No changen=313 Participants	34.2	-
Minimal worseningn=313 Participants	24.3	-
Moderate worseningn=313 Participants	14.1	-
Marked worseningn=313 Participants	2.9	-
Rivastigmine 4.6 mg/24 h Transdermal PatchMarked improvementn=315 Participants	1.3	-
Moderate improvementn=315 Participants	3.5	-
Minimal improvementn=315 Participants	11.4	-
No changen=315 Participants	29.2	-
Minimal worseningn=315 Participants	31.4	-
Moderate worseningn=315 Participants	19.0	-
Marked worseningn=315 Participants	4.1	-

Secondary/registry result

Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the core study

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), Units on a scale	Standard deviation
Rivastigmine 13.3 mg/24 h Transdermal Patchn=313 Participants	-0.4	14.01
Rivastigmine 4.6 mg/24 h Transdermal Patchn=313 Participants	1.2	16.79

Secondary/registry result

Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24

Time frame:Baseline of the core study to Week 24 of the extension study

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of patients	Reported bounds
Rivastigmine 13.3 mg/24 h Transdermal PatchMarked improvementn=381 Participants	1.8	-
Moderate improvementn=381 Participants	5.0	-
Minimal improvementn=381 Participants	9.7	-
No changen=381 Participants	26.2	-
Minimal worseningn=381 Participants	31.5	-
Moderate worseningn=381 Participants	21.5	-
Marked worseningn=381 Participants	4.2	-

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Grossberg GT, Farlow MR, Meng X, Velting DM. Evaluating high-dose rivastigmine patch in severe Alzheimer's disease: analyses with concomitant memantine usage as a factor. Curr Alzheimer Res. 2015;12(1):53-60. doi: 10.2174/1567205011666141218122835.
PMID25523430via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.