Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Minnesota | OTHER |
| Arthritis Foundation | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
"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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A | Experimental | Single Intra-articular Injection of 100 units of Botulinum toxin A in 5 cc of normal saline in the Painful TKA at screening visit |
|
| B | Placebo Comparator | Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Botulinum toxin A | Drug | 100 units of Botulinum toxin A in 5 cc of normal saline in the Painful TKA at screening visit |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 2-month post-injection |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 2-months post-injection |
| Physician Global Assessment of Response to Treatment |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jasvinder Singh, MBBS, MPH | Minneapolis Veterans Affairs Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Minneapolis VA Medical Center | Minneapolis | Minnesota | 55417 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20810509 | Result | Singh JA, Mahowald ML, Noorbaloochi S. Intraarticular botulinum toxin A for refractory painful total knee arthroplasty: a randomized controlled trial. J Rheumatol. 2010 Nov;37(11):2377-86. doi: 10.3899/jrheum.100336. Epub 2010 Sep 1. |
Not provided
Not provided
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
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Intra-articular Placebo | Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Intra-articular Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | all with follow-up data, allowing only single TKA per participant | Posted | Number | participants | 2-month post-injection |
|
6-months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chest pain/new diagnosis of CAD | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Accidental injury | Musculoskeletal and connective tissue disorders | Systematic Assessment | Injury as a result of an accident |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| jasvinder singh | minneapolis VAMC | 205-504-9559 |
Not provided
| ID | Term |
|---|---|
| D010146 | Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D019274 | Botulinum Toxins, Type A |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D001905 | Botulinum Toxins |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Normal Saline | Drug | Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit |
|
|
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)
| 2-month (primary end-point) |
| 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 | 2-month |
| 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 | 2-months |
| 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) | 2-month |
| 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) | 2-month |
| 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 | Upto 6 months |
| 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 | Upto 6-months |
| McGill Affective Dimension | McGill Affective Dimension Score on 0-12 scale at 2-months (higher number is worse) | 2-month |
| 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. | Baseline to 2-months |
| McGill Sensory Pain Score | McGill Sensory pain score on 0-33 at 2-month FU visit (higher score is worse) | 2-month |
| 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. | Baseline to 2-months |
| 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. | Baseline to 2-months |
| 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. | Baseline to 2-months |
| 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. | Baseline to 2-months |
| 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. | Baseline to 2-months |
| pt. wanted to have a surgical procedure |
|
Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit
|
|
| 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 | patients providing pain VAS data at 2-month FU visit | Posted | Mean | Standard Deviation | units on pain VAS scale | 2-months post-injection |
|
|
|
| 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) | 2 patients did not have the outcome assessment; 1 lost to FU | Posted | Number | participants | 2-month (primary end-point) |
|
|
|
| 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 | people providing data at 2-months | Posted | Mean | Standard Deviation | units on a scale | 2-month |
|
|
|
| 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 | patients providing the data | Posted | Mean | Standard Deviation | units on a scale | 2-months |
|
|
|
| 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) | patients providing data | Posted | Mean | Standard Deviation | seconds | 2-month |
|
|
|
| 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) | patients providing data | Posted | Mean | Standard Deviation | units on a scale | 2-month |
|
|
|
| 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 | patients providing data | Posted | Number | participants | Upto 6 months |
|
|
|
| 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 | patients providing the data | Posted | Number | participants | Upto 6-months |
|
|
|
| Secondary | McGill Affective Dimension | McGill Affective Dimension Score on 0-12 scale at 2-months (higher number is worse) | patients providing data | Posted | Mean | Standard Deviation | units on a scale | 2-month |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 2-months |
|
|
|
|
| Secondary | McGill Sensory Pain Score | McGill Sensory pain score on 0-33 at 2-month FU visit (higher score is worse) | patients providing data | Posted | Mean | Standard Deviation | units on a scale | 2-month |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 2-months |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 2-months |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 2-months |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 2-months |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 2-months |
|
|
|
|
| 3 |
| 23 |
| 19 |
| 23 |
| EG001 | Intra-articular Placebo | Single Intra-articular Injection of 5 cc of normal saline in the Painful TKA at screening visit | 9 | 26 | 23 | 26 |
| Supraventricular tachycardia | Cardiac disorders | Systematic Assessment |
|
| Subarachnoid hemorrhage | Cardiac disorders | Systematic Assessment |
|
| Atypical chest pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Seafood allergy | Immune system disorders | Systematic Assessment |
|
| Depression | Psychiatric disorders | Systematic Assessment |
|
| Gouty arthritis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Influenza | Infections and infestations | Systematic Assessment |
|
| Cellulitis and septic arthritis | Infections and infestations | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | Systematic Assessment |
|
| Lethargy and decreased appetite | Nervous system disorders | Systematic Assessment |
|
|
| Pain in the study joint | Musculoskeletal and connective tissue disorders | Systematic Assessment | Pain reported in the joint that underwent injection |
|
| Upper respiratory infections | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Infections of the upper respiratory tract |
|
| Surgical procedure | Surgical and medical procedures | Systematic Assessment | Scheduled surgical procedure |
|
Not provided
Not provided
| D006867 |
| Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
we hypothesized a greater proportion with meaningful reduction in pain on 0-10 scale in intervention versus placebo group. |
| Superiority or Other |