Knee Pain
Conditions
Keywords
Painful Knee Arthroplasty, Botulinum Toxin A, Randomized Controlled Trial, Pain and Function
Brief summary
Primary Total Knee joint replacement surgery is highly successful surgery for relieving pain and improving function in patients with disabling arthritis. Unfortunately, like all biomedical devices, prosthesis failure is a complication of knee replacement surgery that leads to disabling pain, stiffness and loss of function. Approximately 1% of the knee replacements fail every year leading to a 20% failure rate over 20 years. The common causes of failure of prosthetic joint are infection, loosening, trauma or wear of the prosthesis. Currently, a revision surgery is the best option for long term pain relief (analgesics or other pain medications are options but are of limited benefit). Surgery may not be feasible in patients due to advancing age, other medical conditions and surgical/technical difficulties or patient's choice. In addition, the results from revision surgery are not as good as the initial knee joint surgery. Therefore, there is a great need for a novel, targeted therapy that provides an option to patients who are unfit, unable, or unwilling to undergo surgery. In the investigators' recent pilot study, a single injection of Botulinum toxin A (Botox) in painful natural knee, ankle and shoulder joints of patients with various types of arthritis led to significant and durable improvement in pain and function and was safe to use. The investigators propose this 6-month study to compare pain relief, improvement of function and safety of an injection of Botulinum toxin compared to placebo in patients with a painful prosthetic knee joint. Both patients and investigators will be blinded to the treatment assignment to a patient until the study is completed. The investigators will assess the amount and duration of pain relief, improvement in function and short term safety of Botulinum toxin using standard validated measures. Patients will be evaluated at baseline, 2 weeks, 1-, 2-, 3-, 4- and 6-months after a single injection of either placebo or BoNT/A in the hip or knee prosthesis. The six-month follow-up is to assess the duration of meaningful pain relief. If successful, this will offer a new treatment option for patients with a chronically painful knee prosthetic joint, provide more insight into the origin and cause of pain in prosthetic joints and direct future investigations in new directions.
Detailed description
This 6-month randomized, placebo-controlled, double blind trial will compare a single intra-articular (IA) injection of 100 units of Botulinum Toxin A (BoNT/A) to placebo for improvement in pain, function and quality of life (QOL), and safety in patients with painful total knee arthroplasty (TKA). Patients will be recruited at the Minneapolis VA Medical Center. Patients will be eligible if they are over age 18, have TKA, have pain ≥6/10 on 0-10 numeric rating scale (NRS) and are not candidates for revision surgery. The primary outcome is: (1) proportion with clinically meaningful change in pain severity (on 0-10 scale) 2 months after IA injection. The choice of 2-month for primary end-point is based on previous observations from open-label case series in painful TKA. Secondary outcomes will be assessed at each efficacy follow-up (FU) visit. The duration of the trial is 6-months to capture the duration of pain relief. Based on other trials of Botulinum toxin, we expect the peak effect between 2-8 weeks and expect the effect to wear off between 2-4 months. Therefore, for all analyses except duration of pain relief, the efficacy time-points (2 wk, 4 wk, 2 month) and possibly 3- or 4-month (depending on duration of pain relief) will be used. Secondary outcomes include: (1) clinically meaningful pain relief (≥2-point or ≥30% decrease) in pain severity (0-10 scale); (2) change in pain severity at 2 months and at all efficacy time-points; (3) percent with Minimal Clinically Important Improvement on Western Ontario MacMaster Arthritis Index (WOMAC) pain and function sub-scales at 2 months and at all efficacy time-points; (4) amount and duration of pain relief; (5) patient and physician global assessment of response at 2 months and at all efficacy time-points; (6) QOL assessed by WOMAC and Short-form 36 (SF-36) scores at 2 months and at all efficacy time-points; (7) change in function by Timed Stands Test (TST) and Timed-up-and-go (TUG) tests at 2 months and at all efficacy time-points; (8) change in dose of analgesics during the study. We will determine time to onset of and duration of pain relief and time to improvement in function. Safety will be assessed by structured interview form for adverse effects, sensory and manual muscle strength testing, and index joint examination for swelling, erythema and tenderness. At visit #1, after informed consent and screening for inclusion/exclusion criteria, patients will undergo: index joint X-ray, laboratory tests; history, physical examination, index joint pain history, comorbidity and medication history; patient pain assessments, WOMAC and SF-36; and blinded index joint, neurological examination, TST and TUG tests. 50 patients will be randomized to receive either IA BoNT/A 100 units or sterile saline in the index joint. FU phone interviews at 2 and 4-weeks will include pain assessments, WOMAC, patients' global assessment and adverse effects. Interim visits at 2, 3 and 4-months will be identical to visit #1, but will also include patients' and physicians' global assessment and there will be no joint injection. End of study visit at 6 months will be identical to interim visits with the addition of index joint X-ray and laboratory tests. Main analyses will include patients with unilateral TKAs. Sensitivity analyses will be done by including patients with bilateral knees, accounting for correlatedness of observations. Multiple analysis of variance, mixed model regression analyses and/or generalized estimating equations will be used for analysis of continuous and categorical outcomes respectively. Chi-square tests will be used to compare frequency of adverse events. Analysis will be intention-to-treat.
Interventions
DRUGBotulinum toxin A
100 units of Botulinum toxin A in 5 cc of normal saline in the Painful TKA at screening visit
DRUGNormal Saline
Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit
Sponsors
University of Minnesota
Arthritis Foundation
Minneapolis Veterans Affairs Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Male or female subjects, 18 years of age or older. * Written informed consent and written authorization for use or release of health and research study information have been obtained. * Subject has chronic Prosthetic knee joint pain for more than 3 months. * Subject has pain 6 or greater on a 10 point Numerical Pain Rating scale * Ability to follow study instructions and likely to complete all required visits. * Negative urine pregnancy test on the day of treatment prior to the administration of study medication (for females of childbearing potential). (if applicable) * Negative infectious etiology workup (joint aspiration, serological parameters such as Erythrocyte Sedimentation Rate (ESR) or C-reactive protein (CRP) and clinical examination). * Patients who were considered not to be candidates for Prosthetic knee joint revision surgery and have failed traditional treatments including oral pain medications, as determined by referring orthopedic surgeon
Exclusion criteria
* Use of aminoglycoside antibiotics, curare-like agents, or other agents that might interfere with neuromuscular function. * Any medical condition that may put the subject at increased risk with exposure to BOTOX ®including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or known disorders of neuromuscular function * Females who are pregnant, breast-feeding, or planning a pregnancy during the study or who think that they may be pregnant at the start of the study, or females of childbearing potential who are unable or unwilling to use a reliable form of contraception during the study. * Know allergy or sensitivity to any of the components in the study medication. * History of recent or ongoing alcohol or drug abuse. * Known, uncontrolled systemic disease. * Concurrent participation in another research study * Any condition or situation that, in the investigator's opinion, may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study. * Patients whose pain is rated as less than 6 on a 10 point Numerical Pain Rating scale at the screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Clinically Meaningful Improvement in Pain Severity (0-10 cm; Higher Score on Pain Scale is Worse) | 2-month post-injection | 2-point reduction in pain Visual Analog Scale (VAS) from baseline to the 2-month follow-up visit, which is considered clinically meaningful Change in Pain Severity; Pain Severity on VAS ranges from 0 (no pain) to 10 (maximum pain) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physician Global Assessment of Response to Treatment | 2-month (primary end-point) | Physician global assessed on an ordinal scale with very much improved category as the outcome of interest (compared to all other categories of global assessment as reference category) |
| Physical Function Subscale of the WOMAC at 2-months | 2-month | Physical Function subscale score of the WOMAC at 2-months on a 0 (best physical function) to 100 (worst physical function), with higher score indicating worse physical function |
| WOMAC Stiffness (0-100) | 2-months | WOMAC stiffness subscale score on 0-100 scale at 2-month follow-up visit with scores ranging 0 (no joint stiffness) to 100 (worst joint stiffness), with higher score indicating worse joint stiffness |
| Timed Up-and-go (TUG) Test | 2-month | Time to get up from a chair, walk 3 meters turn back and sit in the chair in seconds at the 2-month visit (higher number is worse, i.e., taking a longer time to complete the task is worse) |
| QOL: SF-36 Score Physical Functioning Scale, a Generic Health Status Measure | 2-month | Short Form (SF)-36 physical functioning subscale on 0-100, at 2-month FU visit, as a generic health status measure, with a score ranging from 0 (worst physical functioning) to 100 (best physical functioning), with higher score indicating better physical functioning (higher number is better) |
| Number of Participants With Occurrence of Joint Erythema, Warmth, Swelling or Tenderness | Upto 6 months | Occurence of any of the above clinical features (erythema, warmth, swelling or tenderness) as a new finding compared to the absence of the same feature at baseline |
| Manual Muscle Strength Testing of Knee Flexion and Extension | Upto 6-months | Occurence of decrease in strength of knee flexion or extension at any of the follow-up visits, as measured by the Manual muscle strength testing (MMT) with scores ranging 0-5; 0 indicates None: No visible or palpable contraction; 1 indicates Trace: Visible or palpable contraction with no motion; 2 indicates Poor: Full range of motion (ROM) gravity eliminated; 3 indicates Fair: Full ROM against gravity; 4 indicates Good: Full ROM against gravity, moderate resistance; and 5 indicates Normal: Full ROM against gravity, maximal resistance |
| Mean Pain VAS (0-10) | 2-months post-injection | VAS pain score at 2-month post-injection; Pain Severity on VAS ranges from 0 (no pain) to 10 (maximum pain) with higher score indicating worse pain |
| Change in Serum Cytokine (Interleukin 7) Levels at 2-month Post-injection | Baseline to 2-months | The change in serum interleukin 7 was defined as the difference between the follow-up (2-month) and the baseline value of serum interleukin 7. We compared the mean change in serum interleukin 7 levels between the WOMAC pain responders vs. the WOMAC pain non-responders. |
| McGill Sensory Pain Score | 2-month | McGill Sensory pain score on 0-33 at 2-month FU visit (higher score is worse) |
| Change in Serum Cytokine (Interleukin 10) Levels at 2-month Post-injection | Baseline to 2-months | The change in serum interleukin 10 was defined as the difference between the follow-up (2-month) and the baseline value of serum interleukin 10. We compared the mean change in serum interleukin 10 levels between the WOMAC pain responders vs. the WOMAC pain non-responders. |
| Change in Serum Cytokine (Interleukin 12 p70) Levels at 2-month Post-injection | Baseline to 2-months | The change in serum interleukin 12 p70 was defined as the difference between the follow-up (2-month) and the baseline value of serum interleukin 12 p70. We compared the mean change in serum interleukin 12 p70 levels between the WOMAC pain responders vs. the WOMAC pain non-responders. |
| Change in Serum Cytokine (Eotaxin) Levels at 2-month Post-injection | Baseline to 2-months | The change in serum Eotaxin was defined as the difference between the follow-up (2-month) and the baseline value of serum Eotaxin. We compared the mean change in serum Eotaxin levels between the WOMAC pain responders vs. the WOMAC pain non-responders. |
| Change in Serum Cytokine (Interferon Gamma) Levels at 2-month Post-injection | Baseline to 2-months | The change in serum Interferon Gamma was defined as the difference between the follow-up (2-month) and the baseline value of serum Interferon Gamma. We compared the mean change in serum Interferon Gamma levels between the WOMAC pain responders vs. the WOMAC pain non-responders. |
| Change in Serum Cytokine (Tumor Necrosis Factor Alpha) Levels at 2-month Post-injection | Baseline to 2-months | The change in serum tumor necrosis factor alpha was defined as the difference between the follow-up (2-month) and the baseline value of serum tumor necrosis factor alpha. We compared the mean change in serum tumor necrosis factor alpha levels between the WOMAC pain responders vs. the WOMAC pain non-responders. |
| McGill Affective Dimension | 2-month | McGill Affective Dimension Score on 0-12 scale at 2-months (higher number is worse) |
Countries
United States
Participant flow
Recruitment details
Of the 194 TKAs (188 patients) screened, 60 TKAs (54 patients) were recruited in the 6-month study. Main analyses were performed only on 49 TKAs, after excluding bilateral TKAs, to meet the assumption of independence of observations.
Pre-assignment details
No enrolled participants were excluded from analyses. Main analyses were done for Single TKA per patient, since 6 were bilateral TKAs; sensitivity analyses were done on all, regardless of unilateral or bilateral
Participants by arm
| Arm | Count |
|---|---|
| Intra-articular Botulinum Toxin Single Intra-articular Injection of 100 units of Botulinum toxin A in 5 cc of normal saline in the Painful TKA at screening visit | 25 |
| Intra-articular Placebo Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit | 29 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | pt. wanted to have a surgical procedure | 0 | 1 |
Baseline characteristics
| Characteristic | Intra-articular Botulinum Toxin | Intra-articular Placebo | Total |
|---|---|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 10 | 67 years STANDARD_DEVIATION 12 | 67 years STANDARD_DEVIATION 11 |
| Race/Ethnicity, Customized caucasian | 24 participants | 28 participants | 52 participants |
| Race/Ethnicity, Customized Non-Caucasian | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 20 Participants | 26 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 23 | 23 / 26 |
| serious Total, serious adverse events | 3 / 23 | 9 / 26 |
Outcome results
Primary
Participants With Clinically Meaningful Improvement in Pain Severity (0-10 cm; Higher Score on Pain Scale is Worse)
2-point reduction in pain Visual Analog Scale (VAS) from baseline to the 2-month follow-up visit, which is considered clinically meaningful Change in Pain Severity; Pain Severity on VAS ranges from 0 (no pain) to 10 (maximum pain)
Time frame: 2-month post-injection
Population: all with follow-up data, allowing only single TKA per participant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intra-articular Botulinum Toxin | Participants With Clinically Meaningful Improvement in Pain Severity (0-10 cm; Higher Score on Pain Scale is Worse) | 15 participants |
| Intra-articular Placebo | Participants With Clinically Meaningful Improvement in Pain Severity (0-10 cm; Higher Score on Pain Scale is Worse) | 9 participants |
Secondary
Change in Serum Cytokine (Eotaxin) Levels at 2-month Post-injection
The change in serum Eotaxin was defined as the difference between the follow-up (2-month) and the baseline value of serum Eotaxin. We compared the mean change in serum Eotaxin levels between the WOMAC pain responders vs. the WOMAC pain non-responders.
Time frame: Baseline to 2-months
Population: This protocol modification was made in the middle of the trial conduct, based on a suggestion on the K-12 application. Therefore, the total number of patients with these data is smaller than the total number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | Change in Serum Cytokine (Eotaxin) Levels at 2-month Post-injection | 7.85 pg/ml | Standard Deviation 12.28 |
| Intra-articular Placebo | Change in Serum Cytokine (Eotaxin) Levels at 2-month Post-injection | -2.03 pg/ml | Standard Deviation 13.92 |
p-value: 0.046t-test, 2 sided
Secondary
Change in Serum Cytokine (Interferon Gamma) Levels at 2-month Post-injection
The change in serum Interferon Gamma was defined as the difference between the follow-up (2-month) and the baseline value of serum Interferon Gamma. We compared the mean change in serum Interferon Gamma levels between the WOMAC pain responders vs. the WOMAC pain non-responders.
Time frame: Baseline to 2-months
Population: This protocol modification was made in the middle of the trial conduct, based on a suggestion on the K-12 application. Therefore, the total number of patients with these data is smaller than the total number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | Change in Serum Cytokine (Interferon Gamma) Levels at 2-month Post-injection | 15.61 pg/ml | Standard Deviation 13.35 |
| Intra-articular Placebo | Change in Serum Cytokine (Interferon Gamma) Levels at 2-month Post-injection | -1.24 pg/ml | Standard Deviation 23.18 |
p-value: 0.03t-test, 2 sided
Secondary
Change in Serum Cytokine (Interleukin 10) Levels at 2-month Post-injection
The change in serum interleukin 10 was defined as the difference between the follow-up (2-month) and the baseline value of serum interleukin 10. We compared the mean change in serum interleukin 10 levels between the WOMAC pain responders vs. the WOMAC pain non-responders.
Time frame: Baseline to 2-months
Population: This protocol modification was made in the middle of the trial conduct, based on a suggestion on the K-12 application. Therefore, the total number of patients with these data is smaller than the total number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | Change in Serum Cytokine (Interleukin 10) Levels at 2-month Post-injection | 27.72 pg/ml | Standard Deviation 21.56 |
| Intra-articular Placebo | Change in Serum Cytokine (Interleukin 10) Levels at 2-month Post-injection | 8.51 pg/ml | Standard Deviation 20.9 |
p-value: 0.01t-test, 2 sided
Secondary
Change in Serum Cytokine (Interleukin 12 p70) Levels at 2-month Post-injection
The change in serum interleukin 12 p70 was defined as the difference between the follow-up (2-month) and the baseline value of serum interleukin 12 p70. We compared the mean change in serum interleukin 12 p70 levels between the WOMAC pain responders vs. the WOMAC pain non-responders.
Time frame: Baseline to 2-months
Population: This protocol modification was made in the middle of the trial conduct, based on a suggestion on the K-12 application. Therefore, the total number of patients with these data is smaller than the total number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | Change in Serum Cytokine (Interleukin 12 p70) Levels at 2-month Post-injection | 12.91 pg/ml | Standard Deviation 9.6 |
| Intra-articular Placebo | Change in Serum Cytokine (Interleukin 12 p70) Levels at 2-month Post-injection | 3.36 pg/ml | Standard Deviation 8.17 |
p-value: 0.004t-test, 2 sided
Secondary
Change in Serum Cytokine (Interleukin 7) Levels at 2-month Post-injection
The change in serum interleukin 7 was defined as the difference between the follow-up (2-month) and the baseline value of serum interleukin 7. We compared the mean change in serum interleukin 7 levels between the WOMAC pain responders vs. the WOMAC pain non-responders.
Time frame: Baseline to 2-months
Population: This protocol modification was made in the middle of the trial conduct, based on a suggestion on the K-12 application. Therefore, the total number of patients with these data is smaller than the total number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | Change in Serum Cytokine (Interleukin 7) Levels at 2-month Post-injection | 1.07 pg/ml | Standard Deviation 1.17 |
| Intra-articular Placebo | Change in Serum Cytokine (Interleukin 7) Levels at 2-month Post-injection | 0.08 pg/ml | Standard Deviation 0.91 |
p-value: 0.01t-test, 2 sided
Secondary
Change in Serum Cytokine (Tumor Necrosis Factor Alpha) Levels at 2-month Post-injection
The change in serum tumor necrosis factor alpha was defined as the difference between the follow-up (2-month) and the baseline value of serum tumor necrosis factor alpha. We compared the mean change in serum tumor necrosis factor alpha levels between the WOMAC pain responders vs. the WOMAC pain non-responders.
Time frame: Baseline to 2-months
Population: This protocol modification was made in the middle of the trial conduct, based on a suggestion on the K-12 application. Therefore, the total number of patients with these data is smaller than the total number of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | Change in Serum Cytokine (Tumor Necrosis Factor Alpha) Levels at 2-month Post-injection | 22.22 pg/ml | Standard Deviation 24.65 |
| Intra-articular Placebo | Change in Serum Cytokine (Tumor Necrosis Factor Alpha) Levels at 2-month Post-injection | 4.46 pg/ml | Standard Deviation 21.32 |
p-value: 0.03t-test, 2 sided
Secondary
Manual Muscle Strength Testing of Knee Flexion and Extension
Occurence of decrease in strength of knee flexion or extension at any of the follow-up visits, as measured by the Manual muscle strength testing (MMT) with scores ranging 0-5; 0 indicates None: No visible or palpable contraction; 1 indicates Trace: Visible or palpable contraction with no motion; 2 indicates Poor: Full range of motion (ROM) gravity eliminated; 3 indicates Fair: Full ROM against gravity; 4 indicates Good: Full ROM against gravity, moderate resistance; and 5 indicates Normal: Full ROM against gravity, maximal resistance
Time frame: Upto 6-months
Population: patients providing the data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intra-articular Botulinum Toxin | Manual Muscle Strength Testing of Knee Flexion and Extension | 0 participants |
| Intra-articular Placebo | Manual Muscle Strength Testing of Knee Flexion and Extension | 0 participants |
Secondary
McGill Affective Dimension
McGill Affective Dimension Score on 0-12 scale at 2-months (higher number is worse)
Time frame: 2-month
Population: patients providing data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | McGill Affective Dimension | 3.8 units on a scale | Standard Deviation 3.1 |
| Intra-articular Placebo | McGill Affective Dimension | 4.8 units on a scale | Standard Deviation 3.4 |
Secondary
McGill Sensory Pain Score
McGill Sensory pain score on 0-33 at 2-month FU visit (higher score is worse)
Time frame: 2-month
Population: patients providing data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | McGill Sensory Pain Score | 14.5 units on a scale | Standard Deviation 8 |
| Intra-articular Placebo | McGill Sensory Pain Score | 14.6 units on a scale | Standard Deviation 7.5 |
Comparison: For primary outcome analysis, we compared the proportion of responders with clinically meaningful change \[improvement\] in 0-10 VAS Pain, i.e. those with 2-point reduction in 0-10 VAS pain score at 2-mths, in the 2 groups using comparison of proportions. Proportion of responders were also analyzed at all efficacy timepoints using generalized estimating equation (GEE) modeling. We used GEE for between-group comparisons in secondary outcomes at all efficacy endpoints, adjusted for baseline scores.p-value: <0.05comparison of proportions
Secondary
Mean Pain VAS (0-10)
VAS pain score at 2-month post-injection; Pain Severity on VAS ranges from 0 (no pain) to 10 (maximum pain) with higher score indicating worse pain
Time frame: 2-months post-injection
Population: patients providing pain VAS data at 2-month FU visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | Mean Pain VAS (0-10) | 4.4 units on pain VAS scale | Standard Deviation 2.5 |
| Intra-articular Placebo | Mean Pain VAS (0-10) | 5.7 units on pain VAS scale | Standard Deviation 2.9 |
Secondary
Number of Participants With Occurrence of Joint Erythema, Warmth, Swelling or Tenderness
Occurence of any of the above clinical features (erythema, warmth, swelling or tenderness) as a new finding compared to the absence of the same feature at baseline
Time frame: Upto 6 months
Population: patients providing data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intra-articular Botulinum Toxin | Number of Participants With Occurrence of Joint Erythema, Warmth, Swelling or Tenderness | 0 participants |
| Intra-articular Placebo | Number of Participants With Occurrence of Joint Erythema, Warmth, Swelling or Tenderness | 0 participants |
Secondary
Physical Function Subscale of the WOMAC at 2-months
Physical Function subscale score of the WOMAC at 2-months on a 0 (best physical function) to 100 (worst physical function), with higher score indicating worse physical function
Time frame: 2-month
Population: people providing data at 2-months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | Physical Function Subscale of the WOMAC at 2-months | 48.5 units on a scale | Standard Deviation 14.1 |
| Intra-articular Placebo | Physical Function Subscale of the WOMAC at 2-months | 59.7 units on a scale | Standard Deviation 17.4 |
Secondary
Physician Global Assessment of Response to Treatment
Physician global assessed on an ordinal scale with very much improved category as the outcome of interest (compared to all other categories of global assessment as reference category)
Time frame: 2-month (primary end-point)
Population: 2 patients did not have the outcome assessment; 1 lost to FU
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intra-articular Botulinum Toxin | Physician Global Assessment of Response to Treatment | 6 participants |
| Intra-articular Placebo | Physician Global Assessment of Response to Treatment | 0 participants |
Secondary
QOL: SF-36 Score Physical Functioning Scale, a Generic Health Status Measure
Short Form (SF)-36 physical functioning subscale on 0-100, at 2-month FU visit, as a generic health status measure, with a score ranging from 0 (worst physical functioning) to 100 (best physical functioning), with higher score indicating better physical functioning (higher number is better)
Time frame: 2-month
Population: patients providing data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | QOL: SF-36 Score Physical Functioning Scale, a Generic Health Status Measure | 30.7 units on a scale | Standard Deviation 21.8 |
| Intra-articular Placebo | QOL: SF-36 Score Physical Functioning Scale, a Generic Health Status Measure | 23.6 units on a scale | Standard Deviation 17.5 |
Secondary
Timed Up-and-go (TUG) Test
Time to get up from a chair, walk 3 meters turn back and sit in the chair in seconds at the 2-month visit (higher number is worse, i.e., taking a longer time to complete the task is worse)
Time frame: 2-month
Population: patients providing data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | Timed Up-and-go (TUG) Test | 17.2 seconds | Standard Deviation 18.2 |
| Intra-articular Placebo | Timed Up-and-go (TUG) Test | 9.6 seconds | Standard Deviation 13.8 |
Secondary
WOMAC Stiffness (0-100)
WOMAC stiffness subscale score on 0-100 scale at 2-month follow-up visit with scores ranging 0 (no joint stiffness) to 100 (worst joint stiffness), with higher score indicating worse joint stiffness
Time frame: 2-months
Population: patients providing the data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-articular Botulinum Toxin | WOMAC Stiffness (0-100) | 51.8 units on a scale | Standard Deviation 19.1 |
| Intra-articular Placebo | WOMAC Stiffness (0-100) | 60.4 units on a scale | Standard Deviation 16.3 |