Trial Outcomes & Findings for Comparative Effectiveness Study for Bipolar Disorder (NCT NCT01331304)
NCT ID: NCT01331304
Last Updated: 2018-04-26
Results Overview
The CGI-EI integrates benefits and harms and yields a score that can be compared across interventions. It is made up of 2 subscales: therapeutic effects and side effects. Each rating is on a scale from 1 to 4. To combine these two subscales into the CGI-EI we report as our primary outcome, we subtracted the side effects subscale from the therapeutic effects subscale. Thus, the CGI-EI we report ranges the integers from -3 to +3 (i.e. possible scores are -3,-2,-1,0,1,2,3). A score of -3 is the most burdensome side effect score (4) and the least therapeutic effect score (1) and a score of +3 is the least burdensome side effect score (1) and the highest therapeutic effect score (4). Higher CGI-EI signifies better outcome (minimal side effects, maximal therapeutic effect). Lower CGI-EI signifies worse outcome (maximal side effects, minimal therapeutic effect).To compute CGI-EI score, we subtract the side effect score from the therapeutic effect score.
COMPLETED
PHASE4
482 participants
Average 6 month score minus Average baseline score
2018-04-26
Participant Flow
Participant milestones
| Measure |
Li + APT
Study participants will take lithium in addition to any other medications recommended by the study physician.
Lithium: 600-1200mg per day over 6 months
|
QTP + APT
Study participants will take quetiapine in addition to any other medications recommended by the study physician.
Quetiapine: 100-800mg a day over 6 months
|
|---|---|---|
|
Overall Study
STARTED
|
240
|
242
|
|
Overall Study
COMPLETED
|
182
|
182
|
|
Overall Study
NOT COMPLETED
|
58
|
60
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Comparative Effectiveness Study for Bipolar Disorder
Baseline characteristics by cohort
| Measure |
Li + APT
n=240 Participants
Study participants will take lithium in addition to any other medications recommended by the study physician.
Lithium: 600-1200mg per day over 6 months
|
QTP + APT
n=242 Participants
Study participants will take quetiapine in addition to any other medications recommended by the study physician.
Quetiapine: 100-800mg a day over 6 months
|
Total
n=482 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.6 Years
STANDARD_DEVIATION 12.1 • n=93 Participants
|
39.1 Years
STANDARD_DEVIATION 12.2 • n=4 Participants
|
38.9 Years
STANDARD_DEVIATION 12.1 • n=27 Participants
|
|
Sex: Female, Male
Female
|
140 Participants
n=93 Participants
|
143 Participants
n=4 Participants
|
283 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
100 Participants
n=93 Participants
|
99 Participants
n=4 Participants
|
199 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
240 participants
n=93 Participants
|
242 participants
n=4 Participants
|
482 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Average 6 month score minus Average baseline scoreThe CGI-EI integrates benefits and harms and yields a score that can be compared across interventions. It is made up of 2 subscales: therapeutic effects and side effects. Each rating is on a scale from 1 to 4. To combine these two subscales into the CGI-EI we report as our primary outcome, we subtracted the side effects subscale from the therapeutic effects subscale. Thus, the CGI-EI we report ranges the integers from -3 to +3 (i.e. possible scores are -3,-2,-1,0,1,2,3). A score of -3 is the most burdensome side effect score (4) and the least therapeutic effect score (1) and a score of +3 is the least burdensome side effect score (1) and the highest therapeutic effect score (4). Higher CGI-EI signifies better outcome (minimal side effects, maximal therapeutic effect). Lower CGI-EI signifies worse outcome (maximal side effects, minimal therapeutic effect).To compute CGI-EI score, we subtract the side effect score from the therapeutic effect score.
Outcome measures
| Measure |
Li + APT
n=240 Participants
Study participants will take lithium in addition to any other medications recommended by the study physician.
Lithium: 600-1200mg per day over 6 months
|
QTP + APT
n=242 Participants
Study participants will take quetiapine in addition to any other medications recommended by the study physician.
Quetiapine: 100-800mg a day over 6 months
|
|---|---|---|
|
Clinical Global Impression-Efficacy Index (CGI-EI)
|
1.58 Units on the scale
Interval 1.32 to 1.84
|
1.52 Units on the scale
Interval 1.26 to 1.78
|
PRIMARY outcome
Timeframe: 6 MonthsNecessary Clinical Adjustment (NCA): The Medication Recommendation Tracking Form was developed and successfully implemented in a previous study to capture recommended medication changes at each study visit 17. Clinicians record dosage changes, missed doses, new medications added or discontinued, and specify the reason for each change. Any change in psychotropic medications, or medications used to treat side effects, is coded along with the reason for the change. NCAs include those changes made for lack of effectiveness or intolerance, but not changes for planned dose titrations.
Outcome measures
| Measure |
Li + APT
n=240 Participants
Study participants will take lithium in addition to any other medications recommended by the study physician.
Lithium: 600-1200mg per day over 6 months
|
QTP + APT
n=242 Participants
Study participants will take quetiapine in addition to any other medications recommended by the study physician.
Quetiapine: 100-800mg a day over 6 months
|
|---|---|---|
|
Necessary Clinical Adjustments
|
.8 Mean NCAs per month
Standard Deviation .8
|
.9 Mean NCAs per month
Standard Deviation 1.0
|
SECONDARY outcome
Timeframe: Average baseline score minus Average 6 month scoreThe Framingham risk score captures the classic risk factors for cardiovascular disease, including age, sex, systolic blood pressure, total and high density lipoprotein cholesterol, diabetes mellitus, and smoking. The Framingham risk score is used as a simple predictive tool to determine 10-year (short term) risk for developing cardiovascular disease (CHD), with higher scores indicating higher risk. Established benchmarks exist for scores from 0 to 25--though it can exceed this value--that are meant to translate to the probability of developing heart disease.
Outcome measures
| Measure |
Li + APT
n=240 Participants
Study participants will take lithium in addition to any other medications recommended by the study physician.
Lithium: 600-1200mg per day over 6 months
|
QTP + APT
n=242 Participants
Study participants will take quetiapine in addition to any other medications recommended by the study physician.
Quetiapine: 100-800mg a day over 6 months
|
|---|---|---|
|
Risk of Cardiovascular Disease - Framingham Risk Score
|
-0.26 units on a scale
Interval -0.66 to 0.14
|
0.17 units on a scale
Interval -0.21 to 0.54
|
SECONDARY outcome
Timeframe: Average baseline score minus Average 6-month scoreThe LIFE-RIFT asses the extent to which psychopathology has impacted current functioning in work, household chores, interpersonal relationships with partner, family, and friends, recreational activities, and life, satisfaction, leisure activities and social relationships. Summary scores can range from 4 to 20, with higher scores indicating greater functional impairment.
Outcome measures
| Measure |
Li + APT
n=240 Participants
Study participants will take lithium in addition to any other medications recommended by the study physician.
Lithium: 600-1200mg per day over 6 months
|
QTP + APT
n=242 Participants
Study participants will take quetiapine in addition to any other medications recommended by the study physician.
Quetiapine: 100-800mg a day over 6 months
|
|---|---|---|
|
Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT)
|
-3.74 units on a scale
Interval -4.29 to -3.19
|
-3.61 units on a scale
Interval -4.15 to -3.07
|
Adverse Events
Li + APT
QTP + APT
Serious adverse events
| Measure |
Li + APT
n=240 participants at risk
Study participants will take lithium in addition to any other medications recommended by the study physician.
Lithium: 600-1200mg per day over 6 months
|
QTP + APT
n=242 participants at risk
Study participants will take quetiapine in addition to any other medications recommended by the study physician.
Quetiapine: 100-800mg a day over 6 months
|
|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
1.2%
3/240 • Number of events 3 • Six months
|
0.41%
1/242 • Number of events 1 • Six months
|
|
Psychiatric disorders
Psychiatric Hospitalization
|
7.5%
18/240 • Number of events 23 • Six months
|
5.8%
14/242 • Number of events 19 • Six months
|
|
Injury, poisoning and procedural complications
Car/Bike Accident
|
0.83%
2/240 • Number of events 2 • Six months
|
0.41%
1/242 • Number of events 1 • Six months
|
|
Psychiatric disorders
Suicide
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
|
Cardiac disorders
Death
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
|
Surgical and medical procedures
Laparoscopic Cholecystectomy
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
|
General disorders
Alcoholism Treatment
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
|
Gastrointestinal disorders
Gastrointestinal Issues
|
0.83%
2/240 • Number of events 2 • Six months
|
0.00%
0/242 • Six months
|
|
Renal and urinary disorders
Kidney Infection
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
|
General disorders
Heroin Overdose
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
|
Skin and subcutaneous tissue disorders
Eczema Outbreak
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
|
General disorders
Hospitalization reason unknown
|
0.00%
0/240 • Six months
|
0.41%
1/242 • Number of events 1 • Six months
|
|
Injury, poisoning and procedural complications
Broken Bones
|
0.00%
0/240 • Six months
|
0.83%
2/242 • Number of events 2 • Six months
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/240 • Six months
|
0.83%
2/242 • Number of events 2 • Six months
|
|
Infections and infestations
Flu Hospitalization
|
0.00%
0/240 • Six months
|
0.41%
1/242 • Number of events 1 • Six months
|
|
General disorders
Extreme Sedation Hospitalization
|
0.00%
0/240 • Six months
|
0.41%
1/242 • Number of events 1 • Six months
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms Hospitalization
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
|
Hepatobiliary disorders
Biliary Cirrhosis
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
|
General disorders
Study Medication Overdose
|
0.42%
1/240 • Number of events 1 • Six months
|
0.83%
2/242 • Number of events 2 • Six months
|
|
Nervous system disorders
Pseudoseizure
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cyst
|
0.00%
0/240 • Six months
|
0.41%
1/242 • Number of events 1 • Six months
|
|
Infections and infestations
Staph Infection
|
0.00%
0/240 • Six months
|
0.41%
1/242 • Number of events 1 • Six months
|
|
General disorders
Dizziness
|
0.42%
1/240 • Number of events 1 • Six months
|
0.00%
0/242 • Six months
|
Other adverse events
| Measure |
Li + APT
n=240 participants at risk
Study participants will take lithium in addition to any other medications recommended by the study physician.
Lithium: 600-1200mg per day over 6 months
|
QTP + APT
n=242 participants at risk
Study participants will take quetiapine in addition to any other medications recommended by the study physician.
Quetiapine: 100-800mg a day over 6 months
|
|---|---|---|
|
General disorders
Excessive sleepiness/daytime somnolence
|
28.3%
68/240 • Number of events 96 • Six months
|
76.9%
186/242 • Number of events 249 • Six months
|
|
Nervous system disorders
Headache
|
20.0%
48/240 • Number of events 61 • Six months
|
13.6%
33/242 • Number of events 43 • Six months
|
|
General disorders
Dry Mouth
|
12.1%
29/240 • Number of events 32 • Six months
|
21.1%
51/242 • Number of events 58 • Six months
|
|
Gastrointestinal disorders
Nausea
|
24.2%
58/240 • Number of events 70 • Six months
|
6.2%
15/242 • Number of events 17 • Six months
|
|
General disorders
Increased Weight
|
10.4%
25/240 • Number of events 31 • Six months
|
18.6%
45/242 • Number of events 55 • Six months
|
|
Musculoskeletal and connective tissue disorders
Tremor
|
26.2%
63/240 • Number of events 69 • Six months
|
5.4%
13/242 • Number of events 13 • Six months
|
|
General disorders
Increased Appetite
|
8.3%
20/240 • Number of events 22 • Six months
|
22.7%
55/242 • Number of events 56 • Six months
|
|
Nervous system disorders
Memory/concentration problems
|
11.2%
27/240 • Number of events 32 • Six months
|
8.7%
21/242 • Number of events 25 • Six months
|
|
Nervous system disorders
Dizziness/Lightheaded
|
8.8%
21/240 • Number of events 24 • Six months
|
9.5%
23/242 • Number of events 30 • Six months
|
|
Gastrointestinal disorders
Upset stomach/stomach pain/bloating
|
12.9%
31/240 • Number of events 36 • Six months
|
5.0%
12/242 • Number of events 13 • Six months
|
|
Gastrointestinal disorders
Diarrhea
|
13.3%
32/240 • Number of events 38 • Six months
|
2.9%
7/242 • Number of events 10 • Six months
|
|
Gastrointestinal disorders
Constipation
|
7.9%
19/240 • Number of events 23 • Six months
|
9.1%
22/242 • Number of events 23 • Six months
|
|
General disorders
Increased Thirst
|
12.1%
29/240 • Number of events 32 • Six months
|
1.7%
4/242 • Number of events 4 • Six months
|
|
Renal and urinary disorders
Increased Urinary Frequency
|
13.3%
32/240 • Number of events 33 • Six months
|
0.83%
2/242 • Number of events 3 • Six months
|
|
Musculoskeletal and connective tissue disorders
Stiffness/muscle aches
|
5.4%
13/240 • Number of events 14 • Six months
|
5.8%
14/242 • Number of events 14 • Six months
|
|
Musculoskeletal and connective tissue disorders
Weakness/muscle fatigue
|
4.6%
11/240 • Number of events 12 • Six months
|
5.8%
14/242 • Number of events 15 • Six months
|
|
General disorders
Restless/fidgety (akathisia)
|
2.9%
7/240 • Number of events 7 • Six months
|
6.2%
15/242 • Number of events 17 • Six months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory infection or other cold-like symptoms
|
5.0%
12/240 • Number of events 12 • Six months
|
5.0%
12/242 • Number of events 12 • Six months
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching (myoclonus)
|
2.5%
6/240 • Number of events 6 • Six months
|
5.8%
14/242 • Number of events 14 • Six months
|
|
Skin and subcutaneous tissue disorders
Hair Loss
|
6.7%
16/240 • Number of events 16 • Six months
|
1.7%
4/242 • Number of events 4 • Six months
|
|
Eye disorders
Blurred Vision
|
5.0%
12/240 • Number of events 15 • Six months
|
2.5%
6/242 • Number of events 7 • Six months
|
|
General disorders
Insomnia
|
5.0%
12/240 • Number of events 12 • Six months
|
2.1%
5/242 • Number of events 7 • Six months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place