Trial Outcomes & Findings for Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (NCT NCT02260388)

Last Updated: 2018-07-06

Results Overview

The final outcome of the study is a combination of two endpoints, efficacy and quit or treatment discontinuation rates. The first endpoint was a patient responder-defined measure of efficacy. A patient was deemed efficacious if a 50% or more reduction was observed in the Likert pain-scale from the baseline visit to the 12 week visit (i.e. 6 at baseline to 3 or less at week 12). The second endpoint was the observed percentage of patients who discontinued treatment prior to the last follow up visit for any reason or were lost to follow up. The utility function, which combines efficacy and quit rates, was used to drive the adaptive randomization, stopping criteria, and final analysis conclusions.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

402 participants

Primary outcome timeframe

12 weeks

Results posted on

2018-07-06

Participant Flow

Participant milestones

Participant milestones
Measure	Nortriptyline Nortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. Nortriptyline	Duloxetine Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. Duloxetine	Pregabalin Pregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. Pregabalin	Mexiletine Mexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. Mexiletine
Overall Study STARTED	134	126	73	69
Overall Study COMPLETED	132	118	70	65
Overall Study NOT COMPLETED	2	8	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Nortriptyline Nortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. Nortriptyline	Duloxetine Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. Duloxetine	Pregabalin Pregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. Pregabalin	Mexiletine Mexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. Mexiletine
Overall Study Lost to Follow-up	2	8	3	4

Baseline Characteristics

Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nortriptyline n=134 Participants Nortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. Nortriptyline	Duloxetine n=126 Participants Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. Duloxetine	Pregabalin n=73 Participants Pregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. Pregabalin	Mexiletine n=69 Participants Mexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. Mexiletine	Total n=402 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	91 Participants n=5 Participants	86 Participants n=7 Participants	50 Participants n=5 Participants	41 Participants n=4 Participants	268 Participants n=21 Participants
Age, Categorical >=65 years	43 Participants n=5 Participants	40 Participants n=7 Participants	23 Participants n=5 Participants	28 Participants n=4 Participants	134 Participants n=21 Participants
Age, Continuous	60.3 years STANDARD_DEVIATION 12.7 • n=5 Participants	59.9 years STANDARD_DEVIATION 14.0 • n=7 Participants	59.5 years STANDARD_DEVIATION 13.6 • n=5 Participants	60.7 years STANDARD_DEVIATION 13.7 • n=4 Participants	60.1 years STANDARD_DEVIATION 13.4 • n=21 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	68 Participants n=7 Participants	34 Participants n=5 Participants	28 Participants n=4 Participants	189 Participants n=21 Participants
Sex: Female, Male Male	75 Participants n=5 Participants	58 Participants n=7 Participants	39 Participants n=5 Participants	41 Participants n=4 Participants	213 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	21 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	126 Participants n=5 Participants	119 Participants n=7 Participants	68 Participants n=5 Participants	66 Participants n=4 Participants	379 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	17 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	11 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	26 Participants n=21 Participants
Race (NIH/OMB) White	113 Participants n=5 Participants	104 Participants n=7 Participants	62 Participants n=5 Participants	64 Participants n=4 Participants	343 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	15 Participants n=21 Participants
Region of Enrollment United States	134 Participants n=5 Participants	126 Participants n=7 Participants	73 Participants n=5 Participants	69 Participants n=4 Participants	402 Participants n=21 Participants
Patient-Reported Outcomes Measurement Information System (PROMIS) Scale T-Scores PROMIS Pain Interference T-Score	63.1 T-Score STANDARD_DEVIATION 7.0 • n=5 Participants	62.4 T-Score STANDARD_DEVIATION 6.8 • n=7 Participants	63.3 T-Score STANDARD_DEVIATION 5.5 • n=5 Participants	60.9 T-Score STANDARD_DEVIATION 7.9 • n=4 Participants	62.5 T-Score STANDARD_DEVIATION 6.9 • n=21 Participants
Patient-Reported Outcomes Measurement Information System (PROMIS) Scale T-Scores PROMIS Fatigue T-Score	59.6 T-Score STANDARD_DEVIATION 3.4 • n=5 Participants	59.7 T-Score STANDARD_DEVIATION 3.3 • n=7 Participants	59.1 T-Score STANDARD_DEVIATION 3.7 • n=5 Participants	59.7 T-Score STANDARD_DEVIATION 3.2 • n=4 Participants	59.6 T-Score STANDARD_DEVIATION 3.4 • n=21 Participants
Patient-Reported Outcomes Measurement Information System (PROMIS) Scale T-Scores PROMIS Sleep Disturbance T-Score	59.1 T-Score STANDARD_DEVIATION 9.8 • n=5 Participants	60.6 T-Score STANDARD_DEVIATION 8.3 • n=7 Participants	59.8 T-Score STANDARD_DEVIATION 8.7 • n=5 Participants	57.0 T-Score STANDARD_DEVIATION 11.4 • n=4 Participants	59.3 T-Score STANDARD_DEVIATION 9.5 • n=21 Participants
SF12 Health Component Scores Physical Component Score	38.0 Norm-Based Standardization Score STANDARD_DEVIATION 9.3 • n=5 Participants	38.5 Norm-Based Standardization Score STANDARD_DEVIATION 9.3 • n=7 Participants	37.9 Norm-Based Standardization Score STANDARD_DEVIATION 9.1 • n=5 Participants	41.1 Norm-Based Standardization Score STANDARD_DEVIATION 10.1 • n=4 Participants	38.7 Norm-Based Standardization Score STANDARD_DEVIATION 9.4 • n=21 Participants
SF12 Health Component Scores Mental Component Score	48.0 Norm-Based Standardization Score STANDARD_DEVIATION 10.4 • n=5 Participants	46.7 Norm-Based Standardization Score STANDARD_DEVIATION 10.1 • n=7 Participants	46.8 Norm-Based Standardization Score STANDARD_DEVIATION 11.3 • n=5 Participants	47.2 Norm-Based Standardization Score STANDARD_DEVIATION 11.1 • n=4 Participants	47.2 Norm-Based Standardization Score STANDARD_DEVIATION 10.6 • n=21 Participants
Likert Pain Scale	6.9 units on a scale STANDARD_DEVIATION 1.5 • n=5 Participants	6.7 units on a scale STANDARD_DEVIATION 1.6 • n=7 Participants	6.4 units on a scale STANDARD_DEVIATION 1.6 • n=5 Participants	6.5 units on a scale STANDARD_DEVIATION 1.7 • n=4 Participants	6.7 units on a scale STANDARD_DEVIATION 1.6 • n=21 Participants

PRIMARY outcome

Timeframe: 12 weeks

Outcome measures

Outcome measures
Measure	Nortriptyline n=134 Participants Nortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. Nortriptyline	Duloxetine n=126 Participants Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. Duloxetine	Pregabalin n=73 Participants Pregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. Pregabalin	Mexiletine n=69 Participants Mexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. Mexiletine
Co-Primary Measures: Percent of Patients With at Least a 50% Decrease in Likert Pain Scale From Baseline to Week 12 Follow Up and Percent of Patients That Quit Efficacious and Non-Quit	34 Participants	29 Participants	11 Participants	14 Participants
Co-Primary Measures: Percent of Patients With at Least a 50% Decrease in Likert Pain Scale From Baseline to Week 12 Follow Up and Percent of Patients That Quit Non-Efficacious and Non-Quit	49 Participants	50 Participants	31 Participants	15 Participants
Co-Primary Measures: Percent of Patients With at Least a 50% Decrease in Likert Pain Scale From Baseline to Week 12 Follow Up and Percent of Patients That Quit Quit	51 Participants	47 Participants	31 Participants	40 Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: No secondary data were collected for participants who 'Quit' taking the study medication prior to study completion. Thus, only participants that were deemed efficacious and non-quit, or non-efficacious and non-quit at the primary outcome were collected and analyzed for the secondary outcome measure.

SF-12v2® Health Survey Standard The Optum™ SF-12v2® Health Survey is a shorter version of the SF-36v2® Health Survey that uses just 12 questions to measure functional health and well-being from the patient's point of view. Survey provides psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores. Scores are calibrated so that 50 is the average score or norm, standard deviation = 10. Higher scores indicate better health for both mental and physical component summary scores.

Outcome measures

Outcome measures
Measure	Nortriptyline n=83 Participants Nortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. Nortriptyline	Duloxetine n=79 Participants Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. Duloxetine	Pregabalin n=42 Participants Pregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. Pregabalin	Mexiletine n=29 Participants Mexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. Mexiletine
SF12 Health Composite Scores Mental Component Score	51.0 Norm-Based Standardization Score Standard Deviation 8.9	50.9 Norm-Based Standardization Score Standard Deviation 9.9	47.2 Norm-Based Standardization Score Standard Deviation 11.2	51.3 Norm-Based Standardization Score Standard Deviation 10.8
SF12 Health Composite Scores Physical Component Score	42.8 Norm-Based Standardization Score Standard Deviation 8.7	42.1 Norm-Based Standardization Score Standard Deviation 9.5	40.0 Norm-Based Standardization Score Standard Deviation 8.2	43.7 Norm-Based Standardization Score Standard Deviation 9.6

SECONDARY outcome

Timeframe: 12 weeks

Higher scores for pain interference represents worse outcome (more pain interference) T-score metric: 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. On the T-score metric: A score of 40 is one SD lower than the mean of the reference population; A score of 60 is one SD higher than the mean of the reference population.

Outcome measures

Outcome measures
Measure	Nortriptyline n=83 Participants Nortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. Nortriptyline	Duloxetine n=79 Participants Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. Duloxetine	Pregabalin n=42 Participants Pregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. Pregabalin	Mexiletine n=29 Participants Mexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. Mexiletine
PROMIS Pain Interference Short Form v1.0 8a T Score	56.4 T-Score Standard Deviation 8.4	56.5 T-Score Standard Deviation 8.3	60.0 T-Score Standard Deviation 7.5	54.5 T-Score Standard Deviation 8.8

SECONDARY outcome

Timeframe: 12 Weeks

Higher scores for fatigue represents worse outcome (more fatigue). T-score metric: 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. On the T-score metric: A score of 40 is one SD lower than the mean of the reference population; A score of 60 is one SD higher than the mean of the reference population.

Outcome measures

Outcome measures
Measure	Nortriptyline n=83 Participants Nortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. Nortriptyline	Duloxetine n=79 Participants Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. Duloxetine	Pregabalin n=42 Participants Pregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. Pregabalin	Mexiletine n=29 Participants Mexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. Mexiletine
PROMIS Fatigue Short Form v1.0 8a	53.6 T-Score Standard Deviation 9.5	55.4 T-Score Standard Deviation 10.2	56.7 T-Score Standard Deviation 10.6	51.6 T-Score Standard Deviation 10.7

SECONDARY outcome

Timeframe: 12 weeks

Higher scores for sleep disturbance represents worse outcome (more sleep disturbance). T-score metric: 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. On the T-score metric: A score of 40 is one SD lower than the mean of the reference population; A score of 60 is one SD higher than the mean of the reference population. Higher scores equals more of the concept being measured

Outcome measures

Outcome measures
Measure	Nortriptyline n=83 Participants Nortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. Nortriptyline	Duloxetine n=79 Participants Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. Duloxetine	Pregabalin n=42 Participants Pregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. Pregabalin	Mexiletine n=29 Participants Mexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. Mexiletine
PROMIS Sleep Disturbance Short Form v1.0 8a	58.9 T-Score Standard Deviation 2.5	58.9 T-Score Standard Deviation 2.6	58.3 T-Score Standard Deviation 2.3	59.1 T-Score Standard Deviation 2.0

Adverse Events

Nortriptyline

Serious events: 0 serious events

Other events: 75 other events

Deaths: 0 deaths

Duloxetine

Serious events: 0 serious events

Other events: 59 other events

Deaths: 0 deaths

Pregabalin

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Mexiletine

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Nortriptyline n=134 participants at risk Nortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. Nortriptyline	Duloxetine n=126 participants at risk Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. Duloxetine	Pregabalin n=73 participants at risk Pregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. Pregabalin	Mexiletine n=69 participants at risk Mexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. Mexiletine
Nervous system disorders Dry Mouth	20.1% 27/134 • 12 Weeks Post Randomization	2.4% 3/126 • 12 Weeks Post Randomization	1.4% 1/73 • 12 Weeks Post Randomization	4.3% 3/69 • 12 Weeks Post Randomization
Nervous system disorders Drowsiness/Sleepiness	11.9% 16/134 • 12 Weeks Post Randomization	5.6% 7/126 • 12 Weeks Post Randomization	11.0% 8/73 • 12 Weeks Post Randomization	4.3% 3/69 • 12 Weeks Post Randomization
Ear and labyrinth disorders Nausea	2.2% 3/134 • 12 Weeks Post Randomization	8.7% 11/126 • 12 Weeks Post Randomization	1.4% 1/73 • 12 Weeks Post Randomization	8.7% 6/69 • 12 Weeks Post Randomization
General disorders Insomnia	3.7% 5/134 • 12 Weeks Post Randomization	9.5% 12/126 • 12 Weeks Post Randomization	1.4% 1/73 • 12 Weeks Post Randomization	2.9% 2/69 • 12 Weeks Post Randomization
Nervous system disorders Fatigue	5.2% 7/134 • 12 Weeks Post Randomization	6.3% 8/126 • 12 Weeks Post Randomization	4.1% 3/73 • 12 Weeks Post Randomization	1.4% 1/69 • 12 Weeks Post Randomization
Gastrointestinal disorders Bloating/Constipation	7.5% 10/134 • 12 Weeks Post Randomization	2.4% 3/126 • 12 Weeks Post Randomization	1.4% 1/73 • 12 Weeks Post Randomization	2.9% 2/69 • 12 Weeks Post Randomization
Nervous system disorders Headache	3.0% 4/134 • 12 Weeks Post Randomization	1.6% 2/126 • 12 Weeks Post Randomization	2.7% 2/73 • 12 Weeks Post Randomization	1.4% 1/69 • 12 Weeks Post Randomization
Nervous system disorders Other	2.2% 3/134 • 12 Weeks Post Randomization	10.3% 13/126 • 12 Weeks Post Randomization	16.4% 12/73 • 12 Weeks Post Randomization	13.0% 9/69 • 12 Weeks Post Randomization

Additional Information

Dr. Richard Barohn

University of Kansas Medical Center

Phone: 9139459943

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place