Caboolture Clinical Research Center
Caboolture Clinical Research Center
Gilpin D.,Brisbane Hand and Upper Limb Clinic |
Gilpin D.,Rivercity Private Hospital |
Gilpin D.,Emeritus Research |
Gilpin D.,Caboolture Clinical Research Center |
And 32 more authors.
Journal of Hand Surgery | Year: 2010
Purpose The Collagenase Option for the Reduction of Dupuytren's (CORD) II study investigated the efficacy and safety of injectable Xiaflex (collagenase clostridium histolyticum), in patients with Dupuytren's contracture. Methods This was a prospective, randomized, placebo-controlled trial with 90-day double-blind and 9-month open-label phases. We randomized patients with contractures affecting metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joints 2 to 1 to collagenase (0.58 mg) or placebo. Cords received a maximum of 3 injections. Cord disruption was attempted the day after injection using a standardized finger extension procedure. Primary end point was reduction in contracture to 0° to 5° of normal 30 days after the last injection. Results We enrolled 66 patients; 45 cords (20 MCP to 25 PIP joints) received collagenase and 21 cords (11 MCP to 10 PIP joints) received placebo in the double-blind phase. Statistically significantly more cords injected with collagenase than placebo met the primary end point (44.4% vs 4.8%; p <. 001). The mean percentage decrease in degree of joint contracture from baseline to 30 days after last injection was 70.5% ± 29.2% in the collagenase group and 13.6% ± 26.1% in the placebo group (p < .001). The mean increase in range of motion was significantly greater in the collagenase (35.4° ± 17.8°) than in the placebo (7.6° ± 14.9°; p < .001) group. Efficacy after open-label treatment was similar to that after the double-blind phase: 50.7% of all joints achieved 0° to 5° of normal. More patients were satisfied with collagenase (p < .001). No joint had recurrence of contracture. One patient had a flexion pulley rupture and one patient underwent routine fasciectomy to address cord proliferation and sensory abnormality. No tendon ruptures or systemic allergic reactions were reported. Most adverse events were related to the injection or finger extension procedure. Conclusions Collagenase clostridium histolyticum is the first Food and Drug Administrationapproved, nonsurgical treatment option for adult Dupuytren's contracture patients with a palpable cord that is highly effective and well tolerated. Type of study/level of evidence Therapeutic I. © 2010 American Society for Surgery of the Hand.
Witthaut J.,Uppsala University Hospital |
Witthaut J.,Menzies Research Institute |
Witthaut J.,Tucson Orthopaedic Research Center |
Witthaut J.,Auxilium Pharmaceuticals |
And 32 more authors.
Journal of Hand Surgery | Year: 2013
Purpose: The JOINT I (United States) and JOINT II (Australia and Europe) studies evaluated the efficacy and safety of collagenase clostridium histolyticum (CCH) injection for the treatment of Dupuytren contracture. Methods: Both studies used identical open-label protocols. Patients with fixed-flexion contractures of metacarpophalangeal (MCP) (20° to 100°) or proximal interphalangeal (PIP) joints (20° to 80°) could receive up to three 0.58-mg CCH injections per cord (up to 5 total injections per patient). We performed standardized finger extension procedures to disrupt injected cords the next day, with follow-up 1, 2, 6, and 9 months thereafter. The primary end point (clinical success) was reduction in contracture to within 0° to 5° of full extension 30 days after the last injection. Clinical improvement was defined as 50% or more reduction from baseline contracture. Results: Dupuytren cords affecting 879 joints (531 MCP and 348 PIP) in 587 patients were administered CCH injections at 14 U.S. and 20 Australian/European sites, with similar outcomes in both studies. Clinical success was achieved in 497 (57%) of treated joints using 1.2 ± 0.5 (mean ± SD) CCH injections per cord. More MCP than PIP joints achieved clinical success (70% and 37%, respectively) or clinical improvement (89% and 58%, respectively). Less severely contracted joints responded better than those more severely contracted. Mean change in contracture was 55° for MCP joints and 25° for PIP joints. With average contracture reductions of 73% and improvements in range of motion by 30°, most patients (92%) were "very satisfied" (71%) or "quite satisfied" (21%) with treatment. Physicians rated change from baseline as "very much improved" (47%) or "much improved" (35%). The CCH injections were well tolerated, causing no tendon ruptures or systemic reactions. Conclusions: Collagenase clostridium histolyticum was an effective, minimally invasive option for the treatment of Dupuytren contracture of a broad range of severities. Most treated joints (625 of 879) required a single injection. Treatment earlier in the course of disease provided improved outcomes. Type of study/level of evidence: Therapeutic IV. © 2013 American Society for Surgery of the Hand. Published by Elsevier, Inc. All rights reserved.
Coleman S.,Brisbane Hand and Upper Limb Clinic |
Coleman S.,Indiana Hand to Shoulder Center |
Coleman S.,Caboolture Clinical Research Center |
Coleman S.,Auxilium Pharmaceuticals |
And 28 more authors.
Journal of Hand Surgery | Year: 2014
Purpose To assess the safety and efficacy of 2 concurrent injections of collagenase clostridium histolyticum (CCH) in the same hand to treat multiple Dupuytren flexion contractures. Methods In a multicenter, open-label phase IIIb study, 60 patients received two 0.58-mg CCH doses injected into cords affecting 2 joints in the same hand during 1 visit, followed by finger extension approximately 24 hours later. Efficacy at postinjection day 30 (change in flexion contracture and active range of motion, patient satisfaction, physician-rated improvement, and rates of clinical success [flexion contracture 5 or less]) and adverse events were summarized. Results The concurrent injections were most commonly administered in cords affecting metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints on the same finger (47%) or 2 MCP joints on different fingers of the same hand (37%). Mean total (sum of the 2 treated joints) flexion contracture decreased 76%, from 87 to 24 (MCP joints: 86%; PIP joints: 66%). Mean total range of motion increased from 100 to 161. Clinical success was 76% for MCP joints and 33% for PIP joints. Most patients were very satisfied (60%) or quite satisfied (28%) with treatment. Most investigators rated treated joints as very much improved (55%) or much improved (37%). The most common treatment-related adverse events (> 75% of patients) were contusion, pain in extremity, and edema peripheral (local edema). Most adverse events were mild to moderate in severity. Serious complications included 1 pulley rupture related to study medication and 1 flexor tendon rupture (following conclusion of the study). There were no systemic complications. Conclusions Results suggest that 2 affected joints can be effectively and safely treated with concurrent CCH injections. There was an increased incidence of some adverse events with concurrent treatment (pruritus, lymphadenopathy, blood blister, and skin laceration) compared with treatment of a single joint. High degrees of patient satisfaction and physician-rated improvement were reported. © 2014 by the American Society for Surgery of the Hand. All rights reserved.