Clostridium histolyticum (AA4500) for the Treatment of Adhesive Capsulitis of the Shoulder: A Randomised Double-Blind, Placebo-Controlled Study for the Safety and Efficacy of Collagenase – Single Site Report

Abstract

Background/Hypothesis

Adhesive capsulitis of the shoulder results in pain and restricted movement of the glenohumeral joint. Hypothesis: There would be a difference in active range of movement in the affected shoulder of patients with adhesive capsulitis after receiving a series of injections of collagenase Clostridium histolyticum (CCH) compared to placebo.

Methods

This study reports the results from a single site that was part of a 321-participant, multicenter, double-blind, prospective parallel-group, randomized controlled clinical trial. Inclusion criteria: over 18 years of age, unilateral idiopathic adhesive capsulitis for >3 months, but <12 months. Exclusion criteria: recent physical therapy, injections, subacromial impingement, calcific tendonitis or glenohumeral joint arthritis in the affected shoulder. Subjects were randomized 3:1 to receive CCH 0.58 mg or placebo under ultrasound guidance. Injections were on days 1, 22, and 43. The primary outcome measure was a functional assessment of active range of movement.

Results

Overall, 37 patients were screened, 26 subjects were excluded, and 11 subjects were randomly assigned to the treatment group (n=9) or the control group (n=2). Both control and treatment groups showed improvement in ROM between baseline and day 95. In the treatment group, AROM improved from the baseline of 272.89° (SD 86.25) to 462.11° (SD 96.89) and the control group from 246.00° (SD 5.66) to 451.50° (SD 50.20) at day 95 with no statistical difference between groups p=0.78. Site data were in line with the whole study findings. Treatment-related adverse events at the injection site, including haematoma (bruising) and localised pain and swelling, were common.

Conclusion

Although the participants showed improvement in function, statistical significance was neither reached in the site nor the overall study cohort. Given the adverse events and the potential risks of the procedure, we would not recommend this drug for the treatment of adhesive capsulitis of the shoulder.

Level of Evidence

2, cohort from one site of RCT.

Keywords:

• adhesive capsulitis
• frozen shoulder
• collagenase

Data Sharing Statement

All data relating to this study site are presented in the manuscript. The full data for the study can be found in the supplementary material.

Ethics

This study had site ethics approval from Bellberry 2013-10-535.

Author Contributions

CR wrote the first draft of this manuscript. JF, IK and MR were involved in the editing and final approval of the manuscript. All authors had unrestricted access to the data. JF, CR and MR were involved in the running of the trial site. All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

JF, CR and MR were involved in the trial site and received payments for the running of the trial. IK did not receive funding. No authors declare any other conflict.