Trial Outcomes & Findings for Discontinuing NSAIDs in Veterans With Knee Osteoarthritis (NCT NCT01799213)

Results Overview

The WOMAC pain score has a possible score range of 0-20 for Pain and higher scores indicate worse pain. The WOMAC pain scale consists of 5 questions that ask about pain during walking, stair use, lying in bed at night, sitting, and standing. Each question is scored on a 5-point scale, where 0 = None, 1 = Mild pain, 2 = Moderate pain, 3 = Severe pain, and 4 = Very severe pain. Total pain scores range from 0 to 20 with higher scores reflecting worse pain. The WOMAC also includes a lower extremity disability scale. Both the pain scale and disability scale (17 items) can be analyzed separately.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

490 participants

Primary outcome timeframe

4 Weeks

Results posted on

2023-07-27

Participant Flow

490 participants were enrolled and underwent the run-in; 364 (74%) participants remained eligible at the end of the run-in period and were randomized: 180 to placebo followed by CBT and 184 to meloxicam.

Participant milestones

Participant milestones
Measure	Placebo Followed by CBT Eligible subjects will be randomized to Meloxicam 15 mg po QD vs placebo Cognitive Behavioral Therapy (CBT): Subjects originally assigned to placebo will receive cognitive behavioral therapy for 10 weeks	Active Treatment With Meloxicam Eligible subjects will be randomized to Meloxicam 15 mg po QD vs placebo Meloxicam 15 mg po QD: Eligible subjects will be take Meloxicam 15 mg po QD
Overall Study STARTED	180	184
Overall Study COMPLETED	173	178
Overall Study NOT COMPLETED	7	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Discontinuing NSAIDs in Veterans With Knee Osteoarthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=180 Participants Participants in Placebo (CBT) Arm	Meloxicam n=184 Participants Participants in Meloxicam Arm	Total n=364 Participants Total of all reporting groups
Age, Continuous	58.2 years STANDARD_DEVIATION 11.8 • n=5 Participants	58.5 years STANDARD_DEVIATION 10.0 • n=7 Participants	58.4 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	20 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	161 Participants n=5 Participants	164 Participants n=7 Participants	325 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic White	120 Participants n=5 Participants	112 Participants n=7 Participants	232 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic Black	45 Participants n=5 Participants	51 Participants n=7 Participants	96 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants
WOMAC Pain	5.4 units on a scale STANDARD_DEVIATION 3.8 • n=5 Participants	5.9 units on a scale STANDARD_DEVIATION 3.9 • n=7 Participants	5.6 units on a scale STANDARD_DEVIATION 3.8 • n=5 Participants
WOMAC disability	17.5 units on a scale STANDARD_DEVIATION 12.1 • n=5 Participants	17.9 units on a scale STANDARD_DEVIATION 11.9 • n=7 Participants	17.7 units on a scale STANDARD_DEVIATION 12.0 • n=5 Participants

PRIMARY outcome

Timeframe: 4 Weeks

Population: The WOMAC pain score was available for 84% (152/180) of participants in the placebo group and 92% (169/184) of participants in the meloxicam group four weeks post-randomization.

The WOMAC pain score has a possible score range of 0-20 for Pain and higher scores indicate worse pain. The WOMAC pain scale consists of 5 questions that ask about pain during walking, stair use, lying in bed at night, sitting, and standing. Each question is scored on a 5-point scale, where 0 = None, 1 = Mild pain, 2 = Moderate pain, 3 = Severe pain, and 4 = Very severe pain. Total pain scores range from 0 to 20 with higher scores reflecting worse pain. The WOMAC also includes a lower extremity disability scale. Both the pain scale and disability scale (17 items) can be analyzed separately.

Outcome measures

Outcome measures
Measure	Placebo Followed by CBT n=152 Participants Participants in Placebo (CBT) Arm	Meloxicam n=169 Participants Participants in Meloxicam Arm
Primary Endpoint: WOMAC Pain Score (Likert Scale Version) at 4 Weeks	8.08 units on a scale Standard Error 0.3	6.73 units on a scale Standard Error 0.28

SECONDARY outcome

Timeframe: 14 Weeks

Population: Those with no post-randomization pain measurements (n= 5 in meloxicam group, n= 4 in placebo) were excluded from all analyses of pain, leaving 355 (98%) participants for this analysis.

The AUC is a commonly used measure that combines multiple measurements over a specific time interval into a single index. The AUC provides a single score that quantifies each participant's total WOMAC score across the repeated measurements. The AUC is valid regardless of increases or decreases in reported pain over time. In this case, the possible range is 0-20, with higher scores indicating worse pain.

Outcome measures

Outcome measures
Measure	Placebo Followed by CBT n=176 Participants Participants in Placebo (CBT) Arm	Meloxicam n=179 Participants Participants in Meloxicam Arm
Area Under the Curve (AUC) of the WOMAC Pain Scale Score Over 14 Weeks	7.48 units on a scale*week Standard Error 0.21	6.43 units on a scale*week Standard Error 0.21

SECONDARY outcome

Timeframe: 14 weeks

Population: WOMAC lower extremity disability scores were available in 336 (92%) participants at the end of Phase 2.

Lower extremity disability: Lower extremity functional outcomes will be measured using the WOMAC disability scale. The physical disability scale contains 17 items that assess the amount of difficulty subjects say they have with climbing stairs, rising from a chair, walking, and other activities of daily living. Responses are measured and scored in the same way as the pain scale. The WOMAC lower extremity disability score has a possible score range of 0-68 and higher scores indicate worse functional limitation.

Outcome measures

Outcome measures
Measure	Placebo Followed by CBT n=160 Participants Participants in Placebo (CBT) Arm	Meloxicam n=176 Participants Participants in Meloxicam Arm
Lower Extremity Disability	18.8 score on a scale Standard Error 0.9	19.7 score on a scale Standard Error 0.9

SECONDARY outcome

Timeframe: 14 weeks

Population: Global impression of change was available in 336 (92%) participants at the end of Phase 2

A balanced 5-point scale (rated 1 = Much better to 5 = Much worse) asking subjects to rate their change (if any) in pain since starting the study. The possible range of scores is 1 to 5.

Outcome measures

Outcome measures
Measure	Placebo Followed by CBT n=160 Participants Participants in Placebo (CBT) Arm	Meloxicam n=176 Participants Participants in Meloxicam Arm
Global Impression of Change	2.15 score on a scale Standard Error 0.08	2.30 score on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Weekly, for duration of observation period (14 weeks)

Population: All eligible subjects with any adherence data reported.

* Over the past week, how many days did you use the study drug for your knee pain? * Over the past week, how many days did you use Tylenol or acetaminophen for your knee pain? * Over the past week, how many days did you use other medications that were prescribed by one of your doctors for your knee pain? * Over the past week, how many days did you use other medications, creams or supplements that you got without a prescription for your knee pain? * Over the past week, how many days did you use any medications for a different problem or type of pain (e.g. headache)? Results reported as percentage of study weeks with perfect participant adherence to study medications, with higher percentages indicating higher adherence.

Outcome measures

Outcome measures
Measure	Placebo Followed by CBT n=180 Participants Participants in Placebo (CBT) Arm	Meloxicam n=184 Participants Participants in Meloxicam Arm
Adherence to Study Medication (Assessed in Weeks Adherent)	4 Weeks Adherent Interval 3.0 to 4.0	13 Weeks Adherent Interval 11.0 to 14.0

SECONDARY outcome

Timeframe: Weekly, for duration of observation period (14 weeks)

Population: All eligible subjects with any adherence data reported.

* Over the past week, how many days did you use the study drug for your knee pain? * Over the past week, how many days did you use Tylenol or acetaminophen for your knee pain? * Over the past week, how many days did you use other medications that were prescribed by one of your doctors for your knee pain? * Over the past week, how many days did you use other medications, creams or supplements that you got without a prescription for your knee pain? * Over the past week, how many days did you use any medications for a different problem or type of pain (e.g. headache)? Results reported as percentage of study weeks with perfect participant adherence to study medications, with higher percentages indicating higher adherence.

Outcome measures

Outcome measures
Measure	Placebo Followed by CBT n=184 Participants Participants in Placebo (CBT) Arm	Meloxicam n=180 Participants Participants in Meloxicam Arm
Adherence to Study Medication (Assessed in % of Weeks With Perfect Adherence)	87 % weeks with perfect adherences	91 % weeks with perfect adherences

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Meloxicam

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=180 participants at risk Participants in Placebo (CBT) Arm	Meloxicam n=184 participants at risk Participants in Meloxicam Arm
Gastrointestinal disorders Bleeding hemorrhoid	0.00% 0/180 • Adverse event data were collected through study completion, an average of 14 weeks. After 2-week run-in period where all subjects replaced their current NSAID with the study drug (meloxicam 15mg per day), remaining eligible subjects participated in 4-week, double-blind, placebo-controlled, non-inferiority randomized withdrawal trial (RWT). After 4 weeks, subjects in the meloxicam arm continued study drug. Subjects in the placebo arm stopped the placebo and participated in a 10-week CBT program. All related adverse events were identified by study coordinator or study therapist during the time when subject participates in the study. Any serious adverse events and unanticipated problems involving risks to subjects and others were reported immediately to the study PI and within 24 hrs to the VA Central Institutional Review Board (IRB). The reporting processes, as listed in the VA Central IRB Table of Reporting Requirements, was followed.	0.54% 1/184 • Number of events 1 • Adverse event data were collected through study completion, an average of 14 weeks. After 2-week run-in period where all subjects replaced their current NSAID with the study drug (meloxicam 15mg per day), remaining eligible subjects participated in 4-week, double-blind, placebo-controlled, non-inferiority randomized withdrawal trial (RWT). After 4 weeks, subjects in the meloxicam arm continued study drug. Subjects in the placebo arm stopped the placebo and participated in a 10-week CBT program. All related adverse events were identified by study coordinator or study therapist during the time when subject participates in the study. Any serious adverse events and unanticipated problems involving risks to subjects and others were reported immediately to the study PI and within 24 hrs to the VA Central Institutional Review Board (IRB). The reporting processes, as listed in the VA Central IRB Table of Reporting Requirements, was followed.
Cardiac disorders Chest Pain	0.56% 1/180 • Number of events 1 • Adverse event data were collected through study completion, an average of 14 weeks. After 2-week run-in period where all subjects replaced their current NSAID with the study drug (meloxicam 15mg per day), remaining eligible subjects participated in 4-week, double-blind, placebo-controlled, non-inferiority randomized withdrawal trial (RWT). After 4 weeks, subjects in the meloxicam arm continued study drug. Subjects in the placebo arm stopped the placebo and participated in a 10-week CBT program. All related adverse events were identified by study coordinator or study therapist during the time when subject participates in the study. Any serious adverse events and unanticipated problems involving risks to subjects and others were reported immediately to the study PI and within 24 hrs to the VA Central Institutional Review Board (IRB). The reporting processes, as listed in the VA Central IRB Table of Reporting Requirements, was followed.	1.1% 2/184 • Number of events 2 • Adverse event data were collected through study completion, an average of 14 weeks. After 2-week run-in period where all subjects replaced their current NSAID with the study drug (meloxicam 15mg per day), remaining eligible subjects participated in 4-week, double-blind, placebo-controlled, non-inferiority randomized withdrawal trial (RWT). After 4 weeks, subjects in the meloxicam arm continued study drug. Subjects in the placebo arm stopped the placebo and participated in a 10-week CBT program. All related adverse events were identified by study coordinator or study therapist during the time when subject participates in the study. Any serious adverse events and unanticipated problems involving risks to subjects and others were reported immediately to the study PI and within 24 hrs to the VA Central Institutional Review Board (IRB). The reporting processes, as listed in the VA Central IRB Table of Reporting Requirements, was followed.
Vascular disorders ischemic stroke	0.56% 1/180 • Number of events 1 • Adverse event data were collected through study completion, an average of 14 weeks. After 2-week run-in period where all subjects replaced their current NSAID with the study drug (meloxicam 15mg per day), remaining eligible subjects participated in 4-week, double-blind, placebo-controlled, non-inferiority randomized withdrawal trial (RWT). After 4 weeks, subjects in the meloxicam arm continued study drug. Subjects in the placebo arm stopped the placebo and participated in a 10-week CBT program. All related adverse events were identified by study coordinator or study therapist during the time when subject participates in the study. Any serious adverse events and unanticipated problems involving risks to subjects and others were reported immediately to the study PI and within 24 hrs to the VA Central Institutional Review Board (IRB). The reporting processes, as listed in the VA Central IRB Table of Reporting Requirements, was followed.	0.00% 0/184 • Adverse event data were collected through study completion, an average of 14 weeks. After 2-week run-in period where all subjects replaced their current NSAID with the study drug (meloxicam 15mg per day), remaining eligible subjects participated in 4-week, double-blind, placebo-controlled, non-inferiority randomized withdrawal trial (RWT). After 4 weeks, subjects in the meloxicam arm continued study drug. Subjects in the placebo arm stopped the placebo and participated in a 10-week CBT program. All related adverse events were identified by study coordinator or study therapist during the time when subject participates in the study. Any serious adverse events and unanticipated problems involving risks to subjects and others were reported immediately to the study PI and within 24 hrs to the VA Central Institutional Review Board (IRB). The reporting processes, as listed in the VA Central IRB Table of Reporting Requirements, was followed.
Cardiac disorders Atrial fibrillation	0.56% 1/180 • Number of events 1 • Adverse event data were collected through study completion, an average of 14 weeks. After 2-week run-in period where all subjects replaced their current NSAID with the study drug (meloxicam 15mg per day), remaining eligible subjects participated in 4-week, double-blind, placebo-controlled, non-inferiority randomized withdrawal trial (RWT). After 4 weeks, subjects in the meloxicam arm continued study drug. Subjects in the placebo arm stopped the placebo and participated in a 10-week CBT program. All related adverse events were identified by study coordinator or study therapist during the time when subject participates in the study. Any serious adverse events and unanticipated problems involving risks to subjects and others were reported immediately to the study PI and within 24 hrs to the VA Central Institutional Review Board (IRB). The reporting processes, as listed in the VA Central IRB Table of Reporting Requirements, was followed.	0.00% 0/184 • Adverse event data were collected through study completion, an average of 14 weeks. After 2-week run-in period where all subjects replaced their current NSAID with the study drug (meloxicam 15mg per day), remaining eligible subjects participated in 4-week, double-blind, placebo-controlled, non-inferiority randomized withdrawal trial (RWT). After 4 weeks, subjects in the meloxicam arm continued study drug. Subjects in the placebo arm stopped the placebo and participated in a 10-week CBT program. All related adverse events were identified by study coordinator or study therapist during the time when subject participates in the study. Any serious adverse events and unanticipated problems involving risks to subjects and others were reported immediately to the study PI and within 24 hrs to the VA Central Institutional Review Board (IRB). The reporting processes, as listed in the VA Central IRB Table of Reporting Requirements, was followed.
Infections and infestations Arm celluitis	0.00% 0/180 • Adverse event data were collected through study completion, an average of 14 weeks. After 2-week run-in period where all subjects replaced their current NSAID with the study drug (meloxicam 15mg per day), remaining eligible subjects participated in 4-week, double-blind, placebo-controlled, non-inferiority randomized withdrawal trial (RWT). After 4 weeks, subjects in the meloxicam arm continued study drug. Subjects in the placebo arm stopped the placebo and participated in a 10-week CBT program. All related adverse events were identified by study coordinator or study therapist during the time when subject participates in the study. Any serious adverse events and unanticipated problems involving risks to subjects and others were reported immediately to the study PI and within 24 hrs to the VA Central Institutional Review Board (IRB). The reporting processes, as listed in the VA Central IRB Table of Reporting Requirements, was followed.	0.54% 1/184 • Number of events 1 • Adverse event data were collected through study completion, an average of 14 weeks. After 2-week run-in period where all subjects replaced their current NSAID with the study drug (meloxicam 15mg per day), remaining eligible subjects participated in 4-week, double-blind, placebo-controlled, non-inferiority randomized withdrawal trial (RWT). After 4 weeks, subjects in the meloxicam arm continued study drug. Subjects in the placebo arm stopped the placebo and participated in a 10-week CBT program. All related adverse events were identified by study coordinator or study therapist during the time when subject participates in the study. Any serious adverse events and unanticipated problems involving risks to subjects and others were reported immediately to the study PI and within 24 hrs to the VA Central Institutional Review Board (IRB). The reporting processes, as listed in the VA Central IRB Table of Reporting Requirements, was followed.

Other adverse events

Adverse event data not reported

Additional Information

Lisa G. Suter, MD

Veterans Health Administration, West Haven, CT

Phone: 2039325711

Email: [email protected]; [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place