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Comparative Research of Alzheimer's Disease Drugs (COMET-AD)

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ClinicalTrials.gov Identifier: NCT01362686
Recruitment Status : Terminated (Low study accrual caused the study to be ended early.)
First Posted : May 30, 2011
Results First Posted : February 27, 2017
Last Update Posted : February 27, 2017
Sponsor:
Collaborator:
Agency for Healthcare Research and Quality (AHRQ)
Information provided by (Responsible Party):
Malaz Boustani, MD, MPH, Regenstrief Institute, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Dementia
Alzheimer's Disease
Interventions Drug: Donepezil
Drug: Galantamine
Drug: Rivastigmine
Enrollment 200
Recruitment Details Recruitment took place from 2011-2014. Recruitment took place in geriatric and memory care specialty clinics in an urban setting. Registered nurses, nurse practitioners, and research assistants completed the recruitment and informed consent procedures.
Pre-assignment Details The enrollment goal in the original protocol of the study was 200 patient-caregiver dyads. 200 were enrolled, but it was discovered that 4 dyads were ineligible after enrollment and were not randomized or included in the study which brings the total enrollment to 196. Recruitment was then terminated due to low enrollment rate.
Arm/Group Title Donepezil Galantamine Rivastigmine
Hide Arm/Group Description

See intervention note.

Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

Period Title: Overall Study
Started 67 66 63
Completed 59 54 53
Not Completed 8 12 10
Arm/Group Title Donepezil Galantamine Rivastigmine Total
Hide Arm/Group Description

See intervention note.

Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

Total of all reporting groups
Overall Number of Baseline Participants 67 66 63 196
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 67 participants 66 participants 63 participants 196 participants
79.1  (7.6) 80.1  (9.6) 81.6  (7.8) 80.2  (8.4)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 66 participants 63 participants 196 participants
Female
19
  28.4%
20
  30.3%
12
  19.0%
51
  26.0%
Male
48
  71.6%
46
  69.7%
51
  81.0%
145
  74.0%
1.Primary Outcome
Title Discontinuation Rates
Hide Description We are not seeking to establish efficacy of these three medications for the indication of Alzheimer’s disease. Each of these medications already has FDA-approval for Alzheimer’s. The primary outcome measure is the discontinuation rate among the three medications. Based on previous systematic reviews, these rates are reportedly in the range of 30% by 12 weeks compared with placebo. We will determine the approximate date of discontinuation by self-reports from the caregiver through the telephone-based interview at 6, 12, and 18 weeks.
Time Frame 6, 12, and 18 week interviews from enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Donepezil Galantamine Rivastigmine
Hide Arm/Group Description:

See intervention note.

Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

Overall Number of Participants Analyzed 67 66 63
Measure Type: Number
Unit of Measure: participants
26 35 37
2.Secondary Outcome
Title Neuropsychiatric Inventory (NPI)
Hide Description The NPI is based on a structured interview administered to an informal caregiver and has been adopted by the Alzheimer’s Disease Cooperative Studies Group to obtain information on the presence of psychopathology in behavioral areas including delusions, apathy, hallucinations, disinhibition, agitation, depression, aberrant motor behavior, anxiety, night-time behavior, and euphoria.9 For each of 12 symptoms, if the caregiver reports the presence of psychopathology, a frequency and severity score are multiplied to yield a possible item score range of 0–12, and a possible total score range of 0–144. The NPI can be used to assess changes in the patient’s behavior over the past month. The NPI also assesses the level of caregiver distress attributable to each of the 12 patient behaviors, with a possible total caregiver distress score range of 0–60. Higher scores indicate higher severity of psychopathology and caregiver disress. The NPI has excellent reliability and validity.
Time Frame Baseline, 6, 12, 18 week interviews from enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Donepezil Galantamine Rivastigmine
Hide Arm/Group Description:

See intervention note.

Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

Overall Number of Participants Analyzed 59 58 54
Mean (Standard Deviation)
Unit of Measure: units on a scale
6 WeekNPI Patient 12.71  (17.10) 9.42  (13.21) 8.63  (11.73)
6 Week NPI Caregiver 5.94  (9.09) 4.40  (5.80) 3.91  (4.86)
12 Week NPI Patient 9.62  (13.56) 8.40  (13.27) 5.24  (5.54)
12 Week NPI Caregiver 5.66  (7.34) 4.33  (6.01) 2.22  (2.86)
18 Week NPI Patient 9.06  (13.87) 10.67  (13.85) 7.26  (7.36)
18 Week NPI Caregiver 5.56  (7.66) 6.22  (7.56) 2.89  (3.17)
3.Secondary Outcome
Title Healthy Aging Brain Care (HABC)-Monitor
Hide Description The current HABC-Monitor includes 30 items covering four clinically relevant domains of dementia, ie, cognitive, functional, behavioral, and psychological symptoms, and caregiver quality of life. For brevity and practical use in the clinical setting, each item on the four scales was designed to have the same item response options consisting of four categories that use the frequency of the target problem in the past 2 weeks. The HABC- Monitor took approximately 6 minutes to complete. The scores of the four scales are summed to create the total scores which were used in this analysis.The higher the total score, the higher the level of self reported caregiver burden. The minimum score is 0 and the maximum score is 90.
Time Frame baseline, 6, 12, and 18 week interviews
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Donepezil Galantamine Rivastigmine
Hide Arm/Group Description:

See intervention note.

Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

Overall Number of Participants Analyzed 59 58 54
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline HABC 18.76  (13.64) 18.34  (11.91) 16.61  (11.49)
6 Week HABC 18.61  (15.16) 19.16  (12.72) 16.43  (10.52)
12 Week HABC 16.04  (13.41) 18.00  (15.71) 13.63  (9.34)
18 Week HABC 16.90  (15.30) 19.92  (14.28) 15.80  (9.01)
Time Frame Adverse event data were collected at 6 weeks, 12 weeks, and 18 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Donepezil Galantamine Rivastigmine
Hide Arm/Group Description

See intervention note.

Donepezil: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Galantamine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

See intervention note.

Rivastigmine: The study is open-label and the memory care practice physicians will make determinations about initial drug dosage and any dosage changes and the timing of those changes. These physicians will also make the determination about whether to switch to a different anti-dementia drug, add memantine, or any other agent. We will, of course, monitor the frequency and content of such changes in the natural course of patient care.

All-Cause Mortality
Donepezil Galantamine Rivastigmine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Donepezil Galantamine Rivastigmine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/59 (54.24%)      29/54 (53.70%)      27/53 (50.94%)    
Cardiac disorders       
Fast or Slowed Heart Rate *  5/59 (8.47%)  7 0/54 (0.00%)  0 4/53 (7.55%)  5
Irregular Heart Beat *  4/59 (6.78%)  4 3/54 (5.56%)  4 3/53 (5.66%)  3
Gastrointestinal disorders       
Diahrrhea *  13/59 (22.03%)  17 5/54 (9.26%)  5 7/53 (13.21%)  8
General disorders       
Fainting *  2/59 (3.39%)  2 1/54 (1.85%)  1 2/53 (3.77%)  2
Falls *  0/59 (0.00%)  0 0/54 (0.00%)  0 3/53 (5.66%)  3
Feeling Tired *  7/59 (11.86%)  10 5/54 (9.26%)  7 3/53 (5.66%)  3
Incontinence *  5/59 (8.47%)  6 6/54 (11.11%)  9 5/53 (9.43%)  6
Metabolism and nutrition disorders       
Lack of Interest in Eating *  9/59 (15.25%)  10 3/54 (5.56%)  3 4/53 (7.55%)  4
Musculoskeletal and connective tissue disorders       
Muscle Cramps *  5/59 (8.47%)  7 6/54 (11.11%)  8 3/53 (5.66%)  5
Nervous system disorders       
Dizziness *  4/59 (6.78%)  4 6/54 (11.11%)  10 8/53 (15.09%)  9
Headache *  6/59 (10.17%)  7 4/54 (7.41%)  6 3/53 (5.66%)  4
Pain *  3/59 (5.08%)  5 7/54 (12.96%)  10 4/53 (7.55%)  5
Seizure or Fits *  1/59 (1.69%)  1 1/54 (1.85%)  1 0/53 (0.00%)  0
Psychiatric disorders       
Nightmares *  6/59 (10.17%)  8 3/54 (5.56%)  5 1/53 (1.89%)  1
Respiratory, thoracic and mediastinal disorders       
Asthma *  2/59 (3.39%)  2 5/54 (9.26%)  5 2/53 (3.77%)  2
Runny Nose *  8/59 (13.56%)  9 5/54 (9.26%)  6 4/53 (7.55%)  4
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Donepezil Galantamine Rivastigmine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   40/59 (67.80%)      42/54 (77.78%)      35/53 (66.04%)    
Cardiac disorders       
Fast or Slowed Heart Rate *  5/59 (8.47%)  6 4/54 (7.41%)  5 0/53 (0.00%)  0
Irregular Heart Beat *  3/59 (5.08%)  4 5/54 (9.26%)  5 1/53 (1.89%)  1
Gastrointestinal disorders       
Diahrrhea *  11/59 (18.64%)  12 13/54 (24.07%)  16 9/53 (16.98%)  9
General disorders       
Dizziness *  13/59 (22.03%)  14 12/54 (22.22%)  16 9/53 (16.98%)  9
Fainting *  5/59 (8.47%)  6 2/54 (3.70%)  2 1/53 (1.89%)  1
Falls *  6/59 (10.17%)  7 5/54 (9.26%)  6 4/53 (7.55%)  4
Feeling Tired *  15/59 (25.42%)  21 17/54 (31.48%)  24 14/53 (26.42%)  16
Incontinence *  10/59 (16.95%)  14 10/54 (18.52%)  12 9/53 (16.98%)  13
Metabolism and nutrition disorders       
Lack of Interest in Eating *  12/59 (20.34%)  12 7/54 (12.96%)  8 12/53 (22.64%)  15
Musculoskeletal and connective tissue disorders       
Muscle Cramps *  5/59 (8.47%)  6 6/54 (11.11%)  6 5/53 (9.43%)  10
Nervous system disorders       
Headache *  4/59 (6.78%)  4 9/54 (16.67%)  10 4/53 (7.55%)  6
Pain *  6/59 (10.17%)  6 6/54 (11.11%)  6 6/53 (11.32%)  6
Seizure or Fits *  1/59 (1.69%)  2 2/54 (3.70%)  2 0/53 (0.00%)  0
Psychiatric disorders       
Nightmares *  7/59 (11.86%)  8 5/54 (9.26%)  7 1/53 (1.89%)  1
Respiratory, thoracic and mediastinal disorders       
Asthma *  2/59 (3.39%)  2 5/54 (9.26%)  5 2/53 (3.77%)  2
Runny Nose *  10/59 (16.95%)  17 13/54 (24.07%)  18 8/53 (15.09%)  9
*
Indicates events were collected by non-systematic assessment
Small sample size limits generalizability and may introduce type II error. The study took place at a time when most third-party payers declared donepezil the preferred AChEI due to cost that may have influenced study’s results.
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: Dr. Noll Campbell
Organization: Regenstrief Insitute
Phone: 317-274-9051
Responsible Party: Malaz Boustani, MD, MPH, Regenstrief Institute, Inc.
ClinicalTrials.gov Identifier: NCT01362686     History of Changes
Other Study ID Numbers: R01HS019818-01 ( U.S. AHRQ Grant/Contract )
R01HS019818-01 ( U.S. AHRQ Grant/Contract )
First Submitted: May 26, 2011
First Posted: May 30, 2011
Results First Submitted: July 22, 2016
Results First Posted: February 27, 2017
Last Update Posted: February 27, 2017