TRARO (Traumeel® S in Rotator Cuff Syndrome)-Study

Study Overview
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Brief Summary
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To evaluate functional, clinical, and subjective parameters in patients with rotator cuff syndrome and bursitis treated with Traumeel® S injections versus corticosteroid injections and versus placebo. 160 patients are planned to be randomised (i.e., 64 patients per active treatment group and 32 patients in the placebo group) in 9 investigator sites in Germany, Belgium and Spain. Finally 176 patients have been randomized (73 Traumeel, 67 Fortecortin and 36 Placebo) and 175 of them received at least one dosage of treatment

Detailed Description
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Duration of the study were 16 weeks. Duration of Treatments were 15 days, applying one injection of 2 ml od study medication at days 1, 8, and 15. There was a follow up visit at day 22 (Primary endpoint), a telephone visit at week 9 and a final visit at week 15. Standard descriptive summary statistics were calculated for continuous variables (i.e. arithmetic mean, standard deviation, minimum value, median, maximum value, number of non-missing values). All statistical analyses in this study were of exploratory nature. The summaries of the efficacy parameters, the statistical analyses of the primary efficacy variable, and the statistical analyses of the secondary efficacy variables were performed on the PP Set. These summaries and analyses were supported by corresponding summaries and exploratory statistical analyses performed on the Full Analysis Set. Missing values for all efficacy parameters were imputed by the last observation carried forward (LOCF) approach. The Modified Per-Protocol (MPP) Set excluded from the PP Set also all patients having taken unallowed concomitant medication after Visit 5 and was used as a secondary population for the analysis of efficacy. All statistical tests were two-sided with a significance level of (alpha) = 0.05, unless specified otherwise. The primary efficacy variable was the change from baseline in VAS for abduction rotation pain at Visit 5 (Day 22) (Traumeel® S injections versus corticoid injections) for active external rotation. A one-sided test of non-inferiority of Traumeel® S with respect to dexamethasone at level 0.025 was computed using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and the baseline value of the abduction rotation pain VAS for active external rotation as a covariate. The test decision was based on a one-sided 97.5% confidence interval for the corresponding treatment difference. The non-inferiority margin was set to 13 mm on a 0 - 100 mm VAS scale.

Official Title
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Treatment of Rotator Cuff Syndrome and Bursitis: A Double Blind, Controlled Trial to Assess the Efficacy and Safety of Traumeel® S Injection Versus Corticosteroid Injections and Versus Placebo

Conditions
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Rotator Cuff Syndrome, Shoulder Bursitis

Intervention / Treatment
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* Drug: Traumeel S inj
* Drug: Fortecortin/Dexamethasone 8 mg/2 ml inj
* Drug: Saline inj


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients with acute episodes of chronic rotator cuff syndrome and/or bursitis: tendinopathy of the supraspinatus tendon, bursitis, or partial degenerative tears of the supraspinatus and/or infraspinatus tendon (differentiation by ultrasonography) Age 40 to 65 years, inclusive Willing and able to understand and sign an approved informed consent form Not pregnant (as proven by negative pregnancy test before first study drug administration) or breast-feeding. Females of childbearing potential (including those less than one year post-menopausal) must agree to maintain reliable birth control throughout the study, i.e. an established use of oral, injected or implanted hormonal contraception, female sterilization by hysterectomy, bilateral oophorectomy, or bilateral tubal exeresis, intrauterine device ([IUD] or coil or barrier method (e.g. diaphragm, cervical/vault cap) plus spermicidal cream/gel Exclusion Criteria: Calcifications in shoulder joint Complete rotator cuff tears Treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Previous treatment with NSAIDs is allowed, with a wash-out period of 1 week; paracetamol can be taken until 48 hours before baseline visit Corticoid therapy by mouth or by injection within the previous 3 months prior to screening Any contraindication for corticoid therapy Physical Therapy, acupuncture, transcutaneous electrical nerve stimulation (TENS) and shock-wave therapy (within 30 days prior to screening) Treatment with anticoagulants (except low-dose aspirin) Diabetic patients including borderline cases (glycosylated fraction of hemoglobin [HbA1c] > 7.0% at screening) Clinically significant shoulder joint deformities Major injury, including sports-related injury, to the shoulder within the past year Significant osteoarthritis of the shoulder Cervical spine disorder (that could confound the clinical assessment) that has been symptomatic and required active treatment within the past three months before screening Any active musculoskeletal disease that could confound the diagnosis/evaluation of the painful shoulder, any neurological aetiology of the pain, or any acute infection of the shoulder joint Any major surgery, arthroplasty, or arthroscopy in the signal shoulder within 6 months of screening or planned surgery within the duration of the study Prior history of any malignancy (with the exception of basal cell carcinoma) treated less than 2 years ago Patients with rheumatic polymyalgia Known or suspected allergies against one or any particular ingredients of Traumeel® S or of other study preparations Presence of serious gastrointestinal, renal, hepatic, pulmonary, cardiovascular, neurological disease or other known systemic disease (like leukemia, tuberculosis, immune mediated diseases, multiple sclerosis, Acquired Immuno Deficiency Syndrome, Human Immunodeficiency Virus-infections or other chronic virus-infections) that might interfere with the outcome of the study or the patient's ability to comply with study requirements. Presence of infections and/or skin diseases in the area of the injection site (including psoriasis) Clinically significant abnormal laboratory values (as judged of the investigator) at the screening visit Consumption of any investigational product within one month prior to the screening visit Patients who are likely to be non-compliant or uncooperative during the study, as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Traumeel S inj.<br>Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15 | Drug: Traumeel S inj<br>* Traumeel S inj. 2 ml. subacromial 3 times at days 1, 8 and 15<br>* Other names: Traumeel;|
| Active Comparator: Fortecortin/Dexamethasone 8 mg inj<br>Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15 | Drug: Fortecortin/Dexamethasone 8 mg/2 ml inj<br>* Fortecortin/Dexamethasone 8 mg/2 ml inj. subacromial 3 times at days 1, 8 and 15<br>* Other names: Dexamethasone 8 mg;|
| Placebo Comparator: Saline inj.<br>Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15 | Drug: Saline inj<br>* Saline inj. 2 ml. subacromial 3 times at days 1, 8 and 15<br>* Other names: Placebo inj;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Abduction Rotation Pain VAS at Visit 5 (Day 22) (Traumeel® S Injections Versus Fortecortin) for Active External Rotation | VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain). Change = (Day 22 score -- baseline score). | Baseline to Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 5 (Day 22) | VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain). | Baseline vs. Day 22 | 
| Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 7 (Day 105) | VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain). | Baseline vs. Day 105 | 
| Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Fortecortin at Visit 7 (Day 105) | VAS is a 100 mm visual analogue scale for measuring the pain resulted from the adbuction and external rotation of the arm. Possible scores range from 0 (no pain) to 100 (worst possible pain). | Baseline vs. day 105 | 
| Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22), Traumeel vs Placebo | Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees. | Baseline vs. Day 22 | 
| Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Placebo | Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees. | Baseline vs. day 105 | 
| Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22) Traumeel vs Fortecortin | Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees. | Baseline vs. Day 22 | 
| Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Fortecortin | Range of movement (ROM) changes measured by active external rotation in abduction in degrees by goniometry in the range of 0 to 360 degrees. | Baseline vs. Day 105 | 
| Jobe Test at Visit 5 (Day 15) With Measurement of Pain | This test looked for pain and weakness and was to be examined as active movement. Patients have to stand with shoulders in 90 degrees of abduction, 30 degrees of forward flexion and then internally rotating arm completely i.e., thumb pointing down. This was done to see if the patient was able to resist the clinician's attempts to depress the upper arm to look for muscle weakness. | Baseline vs. Day 22 | 
| Jobe Test at Visit 5 (Day 22) With Measurement of Weakness | This test looked for pain and weakness and was to be examined as active movement. Patients have to stand with shoulders in 90 degrees of abduction, 30 degrees of forward flexion and then internally rotating arm completely i.e., thumb pointing down. This was done to see if the patient was able to resist the clinician's attempts to depress the upper arm to look for muscle weakness. | Baseline vs. day 22 | 
| Painful Arc Test at Visit 5 (Day 22) | The amount of pain that disappeared by further abduction in the range between 60° and 120° was to be measured, with measurement of pain being positive/negative. The idea behind the test is the subacromial space in abduction becomes smaller, whereby compression of the rotator cuff and the subacromial bursa occurs (impingement test). | Baseline vs. day 22 | 
| Change From Baseline in DASH at Visit 5 (Day 22) | The score from the questions answered on the DASH (Disaability of the Arm, Shoulder and Hand) questionnaire were evaluated on both shoulders at screening and on the target shoulder at the later visits. Any changes between the score from baseline was used to evaluate efficacy. The score consists of a basic questionnaire of 30 questions regarding the daily activities with the answer options from no difficulty (value 1) to unable (value 5). The calculation is: ((sum of values of responses/number of responses)-1) X 25. Best possible result is 0, worst possible result is 100. The score may not be calculated if there are more than 3 missing answers. | Baseline vs. Day 22 | 
| Change From Baseline in DASH at Visit 7 (Day 105) | The score from the questions answered on the DASH (Disaability of the Arm, Shoulder and Hand) questionnaire were evaluated on both shoulders at screening and on the The score consists of a basic questionnaire of 30 questions regarding the daily activities with the answer options from no difficulty (value 1) to unable (value 5). The calculation is: ((sum of values of responses/number of responses)-1) X 25. Best possible result is 0, worst possible result is 100. The score may not be calculated if there are more than 3 missing answers.target shoulder at the later visits. Any changes between the score from baseline was used to evaluate efficacy | Baseline vs. Day 105 |