Trial Outcomes & Findings for Comparative Study of Safety and Efficacy of Two Hyaluronic Acids for the Treatment of Knee Osteoarthritis Pain (NCT NCT01295580)
NCT ID: NCT01295580
Last Updated: 2021-04-09
Results Overview
Pain assessment is made of 5 items; each has 5 possible values 0=none, 1=mild, 2=moderate, 3=severe, 4=extreme. The items are summed for a total range of 0 to 20. Therefore, the pain change from baseline range is -20 to 20. A negative change is a reduction in pain from the baseline pain score. A mixed-effect repeated measures regression model was used to estimate a least square mean for the entire "Measured Time Frame". Change from baseline was the dependent variable. Subject baseline score was a fixed effect covariate. Enrollment site, treatment, visit, and treatment by visit interaction were fixed class effects. Subject was a random effect. A least square mean single point estimate and 95%CI was calculated for the entire "Measured Time Frame" using all data collected at each time point within the "Measured Time Frame".
COMPLETED
NA
349 participants
over 18 weeks (week timepoints 6, 10, 14, and 18)
2021-04-09
Participant Flow
Participant milestones
| Measure |
ARTZ
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
Overall Study
STARTED
|
174
|
175
|
|
Overall Study
COMPLETED
|
164
|
167
|
|
Overall Study
NOT COMPLETED
|
10
|
8
|
Reasons for withdrawal
| Measure |
ARTZ
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
Overall Study
Protocol Violation
|
4
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
4
|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Other: inconvenience
|
1
|
0
|
|
Overall Study
Other: family objection
|
0
|
1
|
Baseline Characteristics
Comparative Study of Safety and Efficacy of Two Hyaluronic Acids for the Treatment of Knee Osteoarthritis Pain
Baseline characteristics by cohort
| Measure |
ARTZ
n=174 Participants
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=175 Participants
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
Total
n=349 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.6 years
STANDARD_DEVIATION 8.16 • n=5 Participants
|
60.3 years
STANDARD_DEVIATION 8.11 • n=7 Participants
|
60.4 years
STANDARD_DEVIATION 8.13 • n=5 Participants
|
|
Sex: Female, Male
Female
|
139 Participants
n=5 Participants
|
132 Participants
n=7 Participants
|
271 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Nationality: Han
|
173 participants
n=5 Participants
|
168 participants
n=7 Participants
|
341 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Nationality: Other
|
1 participants
n=5 Participants
|
7 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Region of Enrollment
China
|
174 participants
n=5 Participants
|
175 participants
n=7 Participants
|
349 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: over 18 weeks (week timepoints 6, 10, 14, and 18)Population: per protocol: all subjects randomized and treated with no important protocol deviation(s), which were established at a blinded data review meeting. An important deviation is any deviation that has the potential to bias the primary outcome.
Pain assessment is made of 5 items; each has 5 possible values 0=none, 1=mild, 2=moderate, 3=severe, 4=extreme. The items are summed for a total range of 0 to 20. Therefore, the pain change from baseline range is -20 to 20. A negative change is a reduction in pain from the baseline pain score. A mixed-effect repeated measures regression model was used to estimate a least square mean for the entire "Measured Time Frame". Change from baseline was the dependent variable. Subject baseline score was a fixed effect covariate. Enrollment site, treatment, visit, and treatment by visit interaction were fixed class effects. Subject was a random effect. A least square mean single point estimate and 95%CI was calculated for the entire "Measured Time Frame" using all data collected at each time point within the "Measured Time Frame".
Outcome measures
| Measure |
ARTZ
n=158 Participants
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=161 Participants
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
WOMAC (Western Ontario and McMaster Osteoarthritis Index) Pain Subscale Change From Baseline
|
-5.87 units on a scale
Interval -6.23 to -5.52
|
-5.97 units on a scale
Interval -6.32 to -5.61
|
SECONDARY outcome
Timeframe: over 26 weeks (week 6, 10, 14, 18, and 26)Population: per protocol: all subjects randomized and treated with no important protocol deviation(s), which were established at a blinded data review meeting. An important deviation is any deviation that has the potential to bias the primary outcome.
Pain assessment is made of 5 items; each has 5 possible values 0=none, 1=mild, 2=moderate, 3=severe, 4=extreme. The items are summed for a total range of 0 to 20. Therefore, the pain change from baseline range is -20 to 20. A negative change is a reduction in pain from the baseline pain score. A mixed-effect repeated measures regression model was used to estimate a least square mean for the entire "Measured Time Frame". Change from baseline was the dependent variable. Subject baseline score was a fixed effect covariate. Enrollment site, treatment, visit, and treatment by visit interaction were fixed class effects. Subject was a random effect. A least square mean single point estimate and 95%CI was calculated for the entire "Measured Time Frame" using all data collected at each time point within the "Measured Time Frame".
Outcome measures
| Measure |
ARTZ
n=158 Participants
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=161 Participants
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
WOMAC (Western Ontario and McMaster Osteoarthritis Index) Pain Subscale Change From Baseline
|
-6.05 units on a scale
Interval -6.39 to -5.71
|
-6.15 units on a scale
Interval -6.49 to -5.81
|
SECONDARY outcome
Timeframe: over 18 weeks (week timepoints 6, 10, 14, and 18)Population: per protocol: all subjects randomized and treated with no important protocol deviation(s), which were established at a blinded data review meeting. An important deviation is any deviation that has the potential to bias the primary outcome.
Physical Function assessment is made of 17 items; each has 5 possible values 0=none, 1=mild, 3=moderate, 4=extreme. The items are summed for a total range of 0 to 68. Therefore, the physical function change from baseline range is -68 to 68. A negative change is an improvement in physical function from the baseline physical function score. A mixed-effect repeated measures regression model was used to estimate a least square mean for the entire "Measured Time Frame". Change from baseline was the dependent variable. Subject baseline score was a fixed effect covariate. Enrollment site, treatment, visit, and treatment by visit interaction were fixed class effects. Subject was a random effect. A least square mean single point estimate and 95%CI was calculated for the entire "Measured Time Frame" using all data collected at each time point within the "Measured Time Frame".
Outcome measures
| Measure |
ARTZ
n=158 Participants
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=161 Participants
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
WOMAC (Western Ontario and McMaster Osteoarthritis Index) Physical Function Subscale Change From Baseline
|
-12.10 units on a scale
Interval -12.95 to -11.26
|
-12.75 units on a scale
Interval -13.6 to -11.91
|
SECONDARY outcome
Timeframe: over 26 weeks (week timepoints 6, 10, 14, 18, and 26)Population: per protocol: all subjects randomized and treated with no important protocol deviation(s), which were established at a blinded data review meeting. An important deviation is any deviation that has the potential to bias the primary outcome.
Physical Function assessment is made of 17 items; each has 5 possible values 0=none, 1=mild, 3=moderate, 4=extreme. The items are summed for a total range of 0 to 68. Therefore, the physical function change from baseline range is -68 to 68. A negative change is an improvement in physical function from the baseline physical function score. A mixed-effect repeated measures regression model was used to estimate a least square mean for the entire "Measured Time Frame". Change from baseline was the dependent variable. Subject baseline score was a fixed effect covariate. Enrollment site, treatment, visit, and treatment by visit interaction were fixed class effects. Subject was a random effect. A least square mean single point estimate and 95%CI was calculated for the entire "Measured Time Frame" using all data collected at each time point within the "Measured Time Frame".
Outcome measures
| Measure |
ARTZ
n=158 Participants
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=161 Participants
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
WOMAC (Western Ontario and McMaster Osteoarthritis Index) Physical Function Subscale Change From Baseline
|
-12.58 units on a scale
Interval -13.39 to -11.77
|
-13.16 units on a scale
Interval -13.97 to -12.35
|
SECONDARY outcome
Timeframe: over 18 weeks (week timepoints 6, 10, 14, and 18)Population: per protocol: all subjects randomized and treated with no important protocol deviation(s), which were established at a blinded data review meeting. An important deviation is any deviation that has the potential to bias the primary outcome.
Subject global assessment is one question "Considering all the ways your knee osteoarthritis affects you, how are you doing today?". It has 11 values 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 labeled only at the extremes; 0 = very bad and 10 = very good. The change from baseline range is -10 to 10. A positive change is an improvement from the baseline subject global assessment score. A mixed-effect repeated measures regression model was used to estimate a least square mean for the entire "Measured Time Frame". Change from baseline was the dependent variable. Subject baseline score was a fixed effect covariate. Enrollment site, treatment, visit, and treatment by visit interaction were fixed class effects. Subject was a random effect. A least square mean single point estimate and 95%CI was calculated for the entire "Measured Time Frame" using all data collected at each time point within the "Measured Time Frame".
Outcome measures
| Measure |
ARTZ
n=158 Participants
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=161 Participants
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
Subject Global Assessment Change From Baseline
|
2.55 units on a scale
Interval 2.33 to 2.77
|
2.70 units on a scale
Interval 2.48 to 2.92
|
SECONDARY outcome
Timeframe: over 26 weeks (week timepoints 6, 10, 14, 18, and 26)Population: per protocol: all subjects randomized and treated with no important protocol deviation(s), which were established at a blinded data review meeting. An important deviation is any deviation that has the potential to bias the primary outcome.
Subject global assessment is one question "Considering all the ways your knee osteoarthritis affects you, how are you doing today?". It has 11 values 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 labeled only at the extremes; 0 = very bad and 10 = very good. The change from baseline range is -10 to 10. A positive change is an improvement from the baseline subject global assessment score. A mixed-effect repeated measures regression model was used to estimate a least square mean for the entire "Measured Time Frame". Change from baseline was the dependent variable. Subject baseline score was a fixed effect covariate. Enrollment site, treatment, visit, and treatment by visit interaction were fixed class effects. Subject was a random effect. A least square mean single point estimate and 95%CI was calculated for the entire "Measured Time Frame" using all data collected at each time point within the "Measured Time Frame".
Outcome measures
| Measure |
ARTZ
n=158 Participants
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=161 Participants
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
Subject Global Assessment Change From Baseline
|
2.67 units on a scale
Interval 2.45 to 2.88
|
2.81 units on a scale
Interval 2.59 to 3.02
|
SECONDARY outcome
Timeframe: over 18 weeks (week timepoints 6, 10, 14, and 18)Population: per protocol: all subjects randomized and treated with no important protocol deviation(s), which were established at a blinded data review meeting. An important deviation is any deviation that has the potential to bias the primary outcome.
Knee stiffness assessment is made of 2 items; each has 5 possible values 0=none, 1=mild, 2=moderate, 3=severe, 4=extreme. The items are summed for a total range of 0 to 8. Therefore, the knee stiffness change from baseline range is -8 to 8. A negative change is a reduction in knee stiffness from the baseline knee stiffness score. A mixed-effect repeated measures regression model was used to estimate a least square mean for the entire "Measured Time Frame". Change from baseline was the dependent variable. Subject baseline score was a fixed effect covariate. Enrollment site, treatment, visit, and treatment by visit interaction were fixed class effects. Subject was a random effect. A least square mean single point estimate and 95%CI was calculated for the entire "Measured Time Frame" using all data collected at each time point within the "Measured Time Frame".
Outcome measures
| Measure |
ARTZ
n=158 Participants
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=161 Participants
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
WOMAC (Western Ontario and McMaster Osteoarthritis Index) Knee Stiffness Subscale Change From Baseline
|
-1.73 units on a scale
Interval -1.87 to -1.59
|
-1.87 units on a scale
Interval -2.0 to -1.73
|
SECONDARY outcome
Timeframe: over 26 weeks (week timepoints 6, 10, 14, 18, and 26)Population: per protocol: all subjects randomized and treated with no important protocol deviation(s), which were established at a blinded data review meeting. An important deviation is any deviation that has the potential to bias the primary outcome.
Knee stiffness assessment is made of 2 items; each has 5 possible values 0=none, 1=mild, 2=moderate, 3=severe, 4=extreme. The items are summed for a total range of 0 to 8. Therefore, the knee stiffness change from baseline range is -8 to 8. A negative change is a reduction in knee stiffness from the baseline knee stiffness score. A mixed-effect repeated measures regression model was used to estimate a least square mean for the entire "Measured Time Frame". Change from baseline was the dependent variable. Subject baseline score was a fixed effect covariate. Enrollment site, treatment, visit, and treatment by visit interaction were fixed class effects. Subject was a random effect. A least square mean single point estimate and 95%CI was calculated for the entire "Measured Time Frame" using all data collected at each time point within the "Measured Time Frame".
Outcome measures
| Measure |
ARTZ
n=158 Participants
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=161 Participants
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
WOMAC (Western Ontario and McMaster Osteoarthritis Index) Knee Stiffness Subscale Change From Baseline
|
-1.80 units on a scale
Interval -1.93 to -1.67
|
-1.95 units on a scale
Interval -2.08 to -1.82
|
Adverse Events
ARTZ
DUROLANE
Serious adverse events
| Measure |
ARTZ
n=174 participants at risk
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=175 participants at risk
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/174 • 26 weeks
|
0.57%
1/175 • 26 weeks
|
|
Ear and labyrinth disorders
Otitis media
|
0.57%
1/174 • 26 weeks
|
0.00%
0/175 • 26 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.57%
1/174 • 26 weeks
|
0.00%
0/175 • 26 weeks
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.57%
1/174 • 26 weeks
|
0.00%
0/175 • 26 weeks
|
|
Musculoskeletal and connective tissue disorders
Meniscus lesion
|
0.57%
1/174 • 26 weeks
|
0.00%
0/175 • 26 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.57%
1/174 • 26 weeks
|
0.00%
0/175 • 26 weeks
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/174 • 26 weeks
|
0.57%
1/175 • 26 weeks
|
|
Surgical and medical procedures
Colon polypectomy
|
0.00%
0/174 • 26 weeks
|
0.57%
1/175 • 26 weeks
|
|
Vascular disorders
Cerebral infarction
|
1.1%
2/174 • 26 weeks
|
0.00%
0/175 • 26 weeks
|
Other adverse events
| Measure |
ARTZ
n=174 participants at risk
ARTZ: Hyaluronic acid (five 2.5 mL injections)
|
DUROLANE
n=175 participants at risk
DUROLANE: Hyaluronic acid stabilized (one 3.0 mL injection + four weekly 0 mL sham injections)
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
29/174 • 26 weeks
|
14.9%
26/175 • 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
4.6%
8/174 • 26 weeks
|
7.4%
13/175 • 26 weeks
|
Additional Information
Director, Regulatory and Clinical Affairs
Bioventus, LLC
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place