Trial Outcomes & Findings for Open-label Milnacipran for Persistent Knee Pain One Year After Total Knee Arthroplasty (TKA) (NCT NCT01780389)

Results Overview

The primary outcome is change in pain VAS from baseline to 12 weeks (baseline score minus 12 week or endpoint score; positive number reflects reduction in pain score). The effect size was calculated using the VAS scores measured on a scale of 0 to 100 mm: 0= absence of pain or no pain noted 100 = worst imaginable pain/as bad as can be The higher the score the greater the over all pain intensity.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

5 participants

Primary outcome timeframe

baseline and endpoint 12 weeks

Results posted on

2015-02-06

Participant Flow

Participant milestones

Participant milestones
Measure	Milnacipran Open-label flexibly dosed milnacipran
Overall Study STARTED	5
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Milnacipran Open-label flexibly dosed milnacipran
Overall Study Adverse Event	1

Baseline Characteristics

Open-label Milnacipran for Persistent Knee Pain One Year After Total Knee Arthroplasty (TKA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Milnacipran n=5 Participants Open-label flexibly dosed milnacipran
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and endpoint 12 weeks

The primary outcome is change in pain VAS from baseline to 12 weeks (baseline score minus 12 week or endpoint score; positive number reflects reduction in pain score). The effect size was calculated using the VAS scores measured on a scale of 0 to 100 mm: 0= absence of pain or no pain noted 100 = worst imaginable pain/as bad as can be The higher the score the greater the over all pain intensity.

Outcome measures

Outcome measures
Measure	Milnacipran-Open Label n=5 Participants Open-label flexibly dosed milnacipran for 12 weeks. Twice-daily dosing will be used and the typical titration schedule will be as follows: Day 1 - 12.5 mg every morning Day 2-3 - 12.5 mg twice a day Day 4-7 - 25 mg twice a day Day 8-84 - 50 mg twice a day Taper: Day 85-88 - 25 mg twice a day Day 89-92 - 12.5 twice a day Day 93-96 - 12.5 mg every morning
Change in Pain Visual Analogue Scale(VAS).	44 units on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: between baseline and endpoint (12 weeks or early termination)

KSS measures subjective pain and objective function by joint physical exam. This secondary outcome was the change in Knee Society Score(KSS)from baseline through 12 weeks. KSS scores measured on a scale of 0 to 100 mm: 0 = absence of pain or no pain noted 100= worst imaginable pain/as bad as can be The higher the score the greater the over all pain intensity.

Outcome measures

Outcome measures
Measure	Milnacipran-Open Label n=5 Participants Open-label flexibly dosed milnacipran for 12 weeks. Twice-daily dosing will be used and the typical titration schedule will be as follows: Day 1 - 12.5 mg every morning Day 2-3 - 12.5 mg twice a day Day 4-7 - 25 mg twice a day Day 8-84 - 50 mg twice a day Taper: Day 85-88 - 25 mg twice a day Day 89-92 - 12.5 twice a day Day 93-96 - 12.5 mg every morning
Change in Knee Society Score (KSS).	1.37 units on a scale Standard Deviation 0.76 • Interval 0.76 to 1.37

SECONDARY outcome

Timeframe: Endpoint (12 weeks or early termination)

Population: Data not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to endpoint (12 weeks or early termination)

Measures subjective fatigue.20-item self-report instrument consisting of five scales: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation, and Mental Fatigue. Each scale contains four items rated on a scale of one to 5 with the scale score of one having the anchor of entirely true and the scale score of 5 having the anchor of no, not true. The five scales were identified through factor analysis and are assumed to measure different aspects of fatigue. Lowest possible total score = 20 (absent fatigue) Highest possible total score = 100 (maximum fatigue) Total mean cumulative scores were reported

Outcome measures

Outcome measures
Measure	Milnacipran-Open Label n=5 Participants Open-label flexibly dosed milnacipran for 12 weeks. Twice-daily dosing will be used and the typical titration schedule will be as follows: Day 1 - 12.5 mg every morning Day 2-3 - 12.5 mg twice a day Day 4-7 - 25 mg twice a day Day 8-84 - 50 mg twice a day Taper: Day 85-88 - 25 mg twice a day Day 89-92 - 12.5 twice a day Day 93-96 - 12.5 mg every morning
Change in Total Score of Multidimensional Fatigue Inventory (MFI-20)	0.46 units on a scale Standard Deviation .30

SECONDARY outcome

Timeframe: Baseline to endpoint (12 weeks or early termination)

The secondary outcome measure is change in Beck Depression Inventory. The scale for this inventory is: 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. The higher the score the degree of depression.

Outcome measures

Outcome measures
Measure	Milnacipran-Open Label n=5 Participants Open-label flexibly dosed milnacipran for 12 weeks. Twice-daily dosing will be used and the typical titration schedule will be as follows: Day 1 - 12.5 mg every morning Day 2-3 - 12.5 mg twice a day Day 4-7 - 25 mg twice a day Day 8-84 - 50 mg twice a day Taper: Day 85-88 - 25 mg twice a day Day 89-92 - 12.5 twice a day Day 93-96 - 12.5 mg every morning
Change in the Beck Depression Inventory (BDI-II)	0.49 units on a scale Standard Deviation 0.16 • Interval 0.16 to 0.49

SECONDARY outcome

Timeframe: Between baseline and endpoint (12 weeks or early termination)

Staff-rated assessment of depressive symptoms. Scale is as follows: 0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression

Outcome measures

Outcome measures
Measure	Milnacipran-Open Label n=5 Participants Open-label flexibly dosed milnacipran for 12 weeks. Twice-daily dosing will be used and the typical titration schedule will be as follows: Day 1 - 12.5 mg every morning Day 2-3 - 12.5 mg twice a day Day 4-7 - 25 mg twice a day Day 8-84 - 50 mg twice a day Taper: Day 85-88 - 25 mg twice a day Day 89-92 - 12.5 twice a day Day 93-96 - 12.5 mg every morning
Change in the Montgomery Asberg Depression Rating Scale	0.78 units on a scale Standard Deviation 0.23

SECONDARY outcome

Timeframe: baseline and endpoint (12 weeks or early termination)

Assessment of subjective symptoms of current anxiety and chronic anxiety. There are 20 items for assessing trait anxiety and 20 for state anxiety. State anxiety items include: "I am tense; I am worried" and "I feel calm; I feel secure." Trait anxiety items include: "I worry too much over something that really doesn't matter" and "I am content; I am a steady person." All items are rated on a 4-point scale (e.g., from "Almost Never" to "Almost Always"). Higher scores indicate greater anxiety. Lowest total score is 40 (absent anxiety) Highest total score is 160 (maximum anxiety) Total mean cumulative scores were reported.

Outcome measures

Outcome measures
Measure	Milnacipran-Open Label n=5 Participants Open-label flexibly dosed milnacipran for 12 weeks. Twice-daily dosing will be used and the typical titration schedule will be as follows: Day 1 - 12.5 mg every morning Day 2-3 - 12.5 mg twice a day Day 4-7 - 25 mg twice a day Day 8-84 - 50 mg twice a day Taper: Day 85-88 - 25 mg twice a day Day 89-92 - 12.5 twice a day Day 93-96 - 12.5 mg every morning
Change in Total Score of State Trait Anxiety Inventory (STAI)	0.69 units on a scale Standard Deviation 0.21

SECONDARY outcome

Timeframe: baseline and endpoint (12 weeks or early termination)

Subjective measure of perceived quality of life.The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The eight sections are: * vitality, * physical functioning, * bodily pain, * general health perceptions, * physical role functioning, * emotional role functioning, * social role functioning, * mental health Scale: 0= lowest quality of life 100= high quality of life Higher scores reflect higher quality of life. Total mean cumulative scores were reported.

Outcome measures

Outcome measures
Measure	Milnacipran-Open Label n=5 Participants Open-label flexibly dosed milnacipran for 12 weeks. Twice-daily dosing will be used and the typical titration schedule will be as follows: Day 1 - 12.5 mg every morning Day 2-3 - 12.5 mg twice a day Day 4-7 - 25 mg twice a day Day 8-84 - 50 mg twice a day Taper: Day 85-88 - 25 mg twice a day Day 89-92 - 12.5 twice a day Day 93-96 - 12.5 mg every morning
Change in Total Score of Short Form-36 (SF-36), Measuring Perceived Quality of Life	1.16 units on a scale Standard Deviation 0.47

Adverse Events

Milnacipran

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Milnacipran n=5 participants at risk Open-label flexibly dosed milnacipran
Gastrointestinal disorders Nausea	20.0% 1/5 • Number of events 1 • 12 weeks between baseline visit and week 12 visit.
General disorders Headache	20.0% 1/5 • Number of events 1 • 12 weeks between baseline visit and week 12 visit.
Gastrointestinal disorders constipation	20.0% 1/5 • Number of events 1 • 12 weeks between baseline visit and week 12 visit.
Nervous system disorders painful ejaculation	20.0% 1/5 • Number of events 1 • 12 weeks between baseline visit and week 12 visit.

Additional Information

David Marks, MD

Duke University Medical Center

Phone: 619 668-2859

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place