Clinical trial NCT01702233: TRARO (Traumeel® S in Rotator Cuff Syndrome)-Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rotator Cuff Syndrome
Shoulder Bursitis
Lead sponsor: Biologische Heilmittel Heel GmbH
Sponsor class: INDUSTRY
First posted: 2012-10-08
Enrollment: 175
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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)
2. Age 40 to 65 years, inclusive
3. Willing and able to understand and sign an approved informed consent form
4. 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:

1. Calcifications in shoulder joint
2. Complete rotator cuff tears
3. 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
4. Corticoid therapy by mouth or by injection within the previous 3 months prior to screening
5. Any contraindication for corticoid therapy
6. Physical Therapy, acupuncture, transcutaneous electrical nerve stimulation (TENS) and shock-wave therapy (within 30 days prior to screening)
7. Treatment with anticoagulants (except low-dose aspirin)
8. Diabetic patients including borderline cases (glycosylated fraction of hemoglobin \[HbA1c\] \> 7.0% at screening)
9. Clinically significant shoulder joint deformities
10. Major injury, including sports-related injury, to the shoulder within the past year
11. Significant osteoarthritis of the shoulder
12. Cervical spine disorder (that could confound the clinical assessment) that has been symptomatic and required active treatment within the past three months before screening
13. 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
14. Any major surgery, arthroplasty, or arthroscopy in the signal shoulder within 6 months of screening or planned surgery within the duration of the study
15. Prior history of any malignancy (with the exception of basal cell carcinoma) treated less than 2 years ago
16. Patients with rheumatic polymyalgia
17. Known or suspected allergies against one or any particular ingredients of Traumeel® S or of other study preparations
18. 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.
19. Presence of infections and/or skin diseases in the area of the injection site (including psoriasis)
20. Clinically significant abnormal laboratory values (as judged of the investigator) at the screening visit
21. Consumption of any investigational product within one month prior to the screening visit
22. Patients who are likely to be non-compliant or uncooperative during the study, as judged by the investigator.

Primary outcomes:
measure: Change From Baseline in Abduction Rotation Pain VAS at Visit 5 (Day 22) (Traumeel® S Injections Versus Fortecortin) for Active External Rotation
timeFrame: Baseline to Day 22
Secondary outcomes:
measure: Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 5 (Day 22)
timeFrame: Baseline vs. Day 22
measure: Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Placebo Visit 7 (Day 105)
timeFrame: Baseline vs. Day 105
measure: Change From Baseline in Abduction Rotation Pain VAS for Active External Rotation - Comparison With Fortecortin at Visit 7 (Day 105)
timeFrame: Baseline vs. day 105
measure: Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22), Traumeel vs Placebo
timeFrame: Baseline vs. Day 22
measure: Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Placebo
timeFrame: Baseline vs. day 105
measure: Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 5 (Day 22) Traumeel vs Fortecortin
timeFrame: Baseline vs. Day 22
measure: Changes From Baseline in ROM in Degrees (Active External Rotation in Abduction) After Visit 7 (Day 105), Traumeel vs Fortecortin
timeFrame: Baseline vs. Day 105
measure: Jobe Test at Visit 5 (Day 15) With Measurement of Pain
timeFrame: Baseline vs. Day 22
measure: Jobe Test at Visit 5 (Day 22) With Measurement of Weakness
timeFrame: Baseline vs. day 22
measure: Painful Arc Test at Visit 5 (Day 22)
timeFrame: Baseline vs. day 22
measure: Change From Baseline in DASH at Visit 5 (Day 22)
timeFrame: Baseline vs. Day 22
measure: Change From Baseline in DASH at Visit 7 (Day 105)
timeFrame: Baseline vs. Day 105
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Luc Vandenbossche
Study officials:
affiliation: Physical and Rehabilitation Medicine University Ghent, BE
name: Luc Vandenbossche, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vanden Bossche L, Vanderstraeten G. A multi-center, double-blind, randomized, placebo-controlled trial protocol to assess Traumeel injection vs dexamethasone injection in rotator cuff syndrome: the TRAumeel in ROtator cuff syndrome (TRARO) study protocol. BMC Musculoskelet Disord. 2015 Feb 4;16(1):8. doi: 10.1186/s12891-015-0471-z.