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

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

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

Study Overview

• Status: Completed
• Conditions: Shoulder Bursitis; Rotator Cuff Syndrome
• Intervention / Treatment: Drug: Traumeel S inj; Drug: Fortecortin/Dexamethasone 8 mg/2 ml inj; Drug: Saline inj

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.

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Luc Vandenbossche

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biologische Heilmittel Heel GmbH
• Investigators: Principal Investigator: Luc Vandenbossche, MD, PhD, Physical and Rehabilitation Medicine University Ghent, BE

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: October 4, 2012
• First Submitted That Met QC Criteria: October 5, 2012
• First Posted (Estimate): October 8, 2012

Study Record Updates

• Last Update Posted (Estimate): February 24, 2016
• Last Update Submitted That Met QC Criteria: January 27, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Disease; Joint Diseases; Musculoskeletal Diseases; Rupture; Shoulder Injuries; Tendon Injuries; Syndrome; Rotator Cuff Injuries; Bursitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101
• Other Study ID Numbers: TRARO; 2012-003393-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided