| RCTs |
|---|
First author, year: Badalamente 200264
Secondary reports:
Language: English
Publication type: full text
Number of centres: 1
Setting: University Health Science Centre
Country: USA
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: RCT, Phase II
Randomisation method: NR
Length of follow-up: 5 years (mean for MCP joints = 4 years; PIP joints = 3.8 years)
Source of funding: supported by grants from the US Food and Drug Administration (FD-R- 001437), the National Institutes of Health (General Clinical Research Centre Grant [M01RR1071002]) and the Advance Biofactures Corporation, Lynbrook, NY, USA (A subsidiary of BioSpecifics Technologies, a biopharmaceutical company that has developed injectable collagenase for 12 clinical indications to date) | Enrolled: A: 25; B: 24
Randomised: A: 25; B: 24
Analysed: A: 25; B: 24
Consecutive: yes
Age (years), mean: MCP 65; PIP 64.3
Sex, n (%): MCP: M 31 (86), F 5 (14); PIP: M 11 (84.6), F 2 (15.4)
Primary/previously treated patients: NR
Baseline contracture: mean (SD) degrees MCP joints: 44° (17.4°); PIP joints 53° (18.7°)
Inclusion criteria: patients with either MCP joint contractures or those with PIP joint contractures (only) entered the study
Exclusion criteria: NR | A: collagenase injections at a single dose of 10,000 U. Total volume used was 0.25 ml for MCP joints and 0.20 ml for PIP joints. The results of the first injection were evaluated for 30 days, at days 1, 7, 14, and 30. If the finger contracture did not respond to 0–5° of normal extension (0°) there was a retreatment option for a potential four additional injections using 10,000 U of collagenase on an open-label basis. Subsequent retreatments using 10,000 U of collagenase were based on patient’s response to treatment with clinical success being defined as to within 0–5° of normal extension (0°). If the initial target joint was successfully treated, and if patients presented with other involved joint contractures, these were treated on an open-label basis by using 10,000 U of collagenase. The total maximum dose that a patient could receive was 50,000 U of collagenase with an interval of 4–6 weeks between each retreatment injection. On day 1 after injection a therapist fitted the patients with a night extension splint that was to be worn for 4 months. Patients were also instructed by the therapist to do extension exercises at home. Daily vitamin E massage for 4 months was also suggested to keep the treatment area soft and pliable. Serial follow-up examinations occurred on days 7 and 14 and at months 1, 2, 3, 6, 9 and 12
B: placebo – consisted of sterile normal saline containing 2 mmol/l calcium chloride | Reduction of contracture to within 5°, adverse events, ROM, grip strength |
First author, year: Badalamente 200563
Secondary reports:
Language: English
Publication type: abstract
Number of centres: NR
Setting: NR
Country: USA
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: RCT, Phase III (followed by open-label extension)
Randomisation method: NR
Length of follow-up: mean 125 days for MCP joints/107 days for PIP joints
Source of funding: FDA (Grant 001437), the NIH (GCRC-M01RR10710) and the Biospecifics Technologies Corp. | Enrolled: 35
Randomised: NR
Analysed: NR
Consecutive: yes
Age (years): NR
Sex n (%): NR
Primary/previously treated patients: NR
Baseline contracture: mean MCP joints: 45°; PIP joints 43°
Inclusion criteria: NR
Exclusion criteria: NR | A: collagenase injections, 0.58 mg (0.25 ml for MCP joints and 0.20 ml for PIP joints). Maximum three injections
B: saline placebo, maximum three injections | Reduction of contracture, adverse events |
First author, year: Badalamente 200765
Secondary reports:
Language: English
Publication type: full text
Number of centres: NR
Setting: NR
Country: USA
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: RCT, Phase III (followed by open-label extension)
Randomisation method: joints were randomised in a 2 : 1 ratio to receive 10,000 U of collagenase
Length of follow-up: up to 12 months
Source of funding: FDA (Grant 001437), the NIH (GCRC-M01RR10710) and the Biospecifics Technologies Corp. | Enrolled: A: 23 B: 12
Randomised: A: 23 B: 12
Analysed: NR
Consecutive: yes
Age (years), mean (SD): A: 60.1 (7.6); B: 63.8 (10.0)
Sex, n (%): A + B: M 28 (80); F 7 (20)
Primary/previously treated patients: NR
Baseline contracture: mean (SD): MCP joints: 51° (12°); PIP joints 46° (14°)
Inclusion criteria: age ≥ 18 years; fixed flexion deformity of ≥ 20° of the MCP or PIP joints in at least one finger
Exclusion criteria: NR | A: collagenase injections, 0.58 mg (0.25 ml for MCP joints and 0.20 ml for PIP joints). Maximum three injections. All patients were splinted at night for an interval of 4 months after the last injection was administered
B: saline placebo, maximum 3 injections | Reduction of contracture, adverse events |
First author, year: Gilpin 201056 (CORD II)
Secondary reports:
Language: English
Publication type: full text
Number of centres: 5
Setting: multiple hospital sites
Country: Australia
Start/end dates: August 2007 to September 2008
Prospective/retrospective data collection: prospective
Study design: RCT, Phase III (with open-label extension)
Randomisation method: randomisation achieved with the use of a computer-generated permuted block design (block size of 6) within each baseline severity level for each study site. Patients were randomly assigned to receive collagenase or placebo in the double-blind phase in a 2 : 1 ratio, to maximise the number of patients who could benefit with active treatment versus placebo
Length of follow-up: double-blind phase: 90 days
Open-label extension: 12 months
Source of funding: Auxilium Pharmaceuticals | Enrolled: A: 45; B: 21
Randomised: A: 45; B: 21
Analysed: A: 45; B: 21
Consecutive: yes
Age (years), mean (SD): A: 63 (7.8); B: 65.5 (11.1)
Sex, n (%): A: M 39 (86.7); F 6 (13.3); B: M 17 (81); F 4 (19)
Primary/previously treated patients: both
Baseline contracture: mean (SD) total contracture index A: 174.7° (107.2°); B: 150.1° (84°)
Inclusion criteria: good health, aged ≥ 18 years; MCP joint contracture ≥ 20° and ≤ 100°; PIP joint contracture ≥ 20° and ≤ 80° in at least one digit (not the thumb); inability to simultaneously place the affected finger and palm flat on a table. Women were required to be postmenopausal or using contraception. Patients with recurrent disease were eligible for study participation if other eligibility criteria were met
Exclusion criteria: breastfeeding or pregnancy; bleeding disorder; recent stroke; previous treatment of the primary joint within 90 days of first dose of study drug; collagenase treatment or treatment with any investigational drug within 30 days of first dose of study drug; use of a tetracycline derivative within 14 days of first dose of study drug; anticoagulant within 7 days of first dose of study drug (with the exception of low-dose aspirin); allergy to collagenase; and chronic muscular, neurological, or neuromuscular disorders affecting the hands | A: collagenase injection (0.58 mg per injection). When needed, a standardised finger extension procedure was implemented up to three times the day after injection to facilitate cord disruption. After the finger extension procedure, patients were instructed to wear night splints for up to 4 months, perform at-home finger flexion and extension exercises, and return to normal daily activities. Each affected cord could undergo a maximum of three treatment cycles in 30-day intervals, and each patient could receive a maximum of eight treatment cycles during the 12-month study. During the 90-day double-blind phase, if the primary joint (first treated joint) met the primary end point in fewer than three treatment cycles, a second joint could be treated. If the first and second joints met the primary end point with one treatment cycle each, a third joint could be treated. During the 9-month open-label phase, treatment was at the discretion of the investigator. Patients from the double-blind phase who still required collagenase treatment could receive up to five additional collagenase injections in the open-label phase. These included patients who received placebo treatment, patients who did not achieve clinical success with fewer than three collagenase injections, and patients who had other Dupuytren’s cords that were not injected with collagenase
B: placebo (lyophilised Tris and sucrose only) and treated as above | Reduction of contracture, recurrence, adverse events |
First author, year: Hurst 200955 (CORD I)
Secondary reports: Witthaut 201166
Language: English
Publication type: full text
Number of centres: 16
Setting: Multiple hospital sites
Country: USA
Start/end dates: August 2007 to October 2008
Prospective/retrospective data collection: prospective
Study design: RCT, Phase III (with open-label extension)
Randomisation method: patients were randomised with a centralised interactive voice response system to active treatment or placebo with a ratio of 2 : 1 in favour of the active treatment within each joint type/baseline severity strata. Equal allocation to treatment groups was deemed unnecessary because of the anticipated high rate of clinical success. Randomisation was achieved with the use of a permuted-block design (block size of 6) with random assignment within each stratum for each study site
Length of follow-up: 30 days
Source of funding: Auxilium Pharmaceuticals | Enrolled: A: 204; B:104
Randomised: A: 204; B:104
Analysed: A: 203; B 103
Consecutive: yes
Age (years), mean (SD): A: 62.3 (9.7); B: 63.3 (9.1)
Sex, n (%): A: M 171 (83.8%), F 33 (16.2%); B: M 74 (71.2%), F 30 (28.8%)
Primary/previously treated patients: both
Baseline contracture: mean (SD) total contracture index A: 149.1° (127.6°); B: 149.3°(111.4°)
Inclusion criteria: aged > 18 years; diagnosis of DC, with a fixed flexion deformity of at least one finger, other than the thumb, that had a contracture at least 20°, but not greater than 100°, for MCP (80° for PIP) joints, caused by a palpable cord that had never been treated with collagenase; a positive ‘table top test,’ defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top; judged to be in good health
Women included in the study were postmenopausal or used contraception
Exclusion criteria: breastfeeding or pregnancy, a bleeding disorder, a recent stroke, previous treatment of the primary joint within 90 days before the beginning of the study, collagenase treatment or treatment with any investigational drug within 30 days before the beginning of the study, the use of a tetracycline derivative within 14 days before the beginning of the study, the use of an anticoagulant within 7 days before the beginning of the study, an allergy to collagenase and a chronic muscular, neurological, or neuromuscular disorder affecting the hands | A: Collagenase clostridium histolyticum (0.58 mg per injection) was reconstituted in 0.25 ml of sterile diluent (for MCP joints) or 0.20 ml of sterile diluent (for PIP joints) and injected directly into the affected cords. If needed, the joints were then manipulated up to three times with the use of a standardised procedure the day after injection in an effort to rupture the cords. Patients were given a splint to wear nightly for up to 4 months
B: Placebo (10 mM Tris per 60 mM sucrose reconstituted in diluent) was administered in a similar manner. Subjects could have received up to three injections of placebo into the cord of the affected hand. Each injection was separated by at least 30 days. Individual cords may have received up to a maximum of three injections | Reduction of contracture, ROM, recurrence, adverse events |
| Non-randomised comparative studies |
First author, year: Naam 201371
Secondary reports:
Language: English
Publication type: full text
Number of centres: 1
Setting: Hospital surgery department
Country: USA
Start/end dates: NR
Prospective/retrospective data collection: retrospective
Study design: non-randomised, comparative, patient chart-review
Length of follow-up: 2 years
Source of funding: Auxilium Pharmaceuticals | Enrolled: A: 25; B 21
Analysed: A: 25; B 21
Consecutive: NR
Age (years), mean (range): A: 65 (42–83); 67 (39–84)
Sex, n (%): A: M 23 (92), F 2 (8); M 13 (62), F 8 (38)
Primary/previously treated patients: NR
Baseline contracture: mean degrees A: 43.5°; B: 41.4°
Inclusion criteria: DC with a fixed-flexion deformity > 20 and < 100°, measured by finger goniometry for MCP joints and > 20 and < 80° for PIP joints in at least one finger other than the thumb caused by a palpable cord
Exclusion criteria: NR | A: injection of 0.58 mg dose of collagenase – 0.25 ml for MCP joints; 0.02 ml for PIP joints. Approximately 24 hours post-injection, a finger-extension procedure was conducted to facilitate cord disruption. Finger-extension consisted of manipulation of the treated finger, recommended no more than three times regardless of whether or not the cord ruptured. Hand therapists were involved in fitting all patients with a night splint to be worn for 3 months following each injection and finger extension procedure
B: open fasciectomy with multiple Z-plasties was performed under axillary block anaesthesia. Multiple Z-plasties were performed at the level of the distal palmar crease, proximal digital crease and PIP joint flexion crease. The hand was splinted with full extension of the digit and slight extension of the wrist. Postoperatively, the splint was removed in 2–3 days and the patient was started on AROM exercises. The patient continued to wear a night splint for 3 months following the surgery | Reduction of contracture, ROM, adverse events, time to normal function, health-related quality of life |
First author, year: Nydick 201372
Secondary reports:
Language: English
Publication type: full text
Number of centres: 1
Setting: orthopaedic institute
Country: USA
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: non-randomised, comparative, patient chart-review
Length of follow-up: mean 6 months
Source of funding: NR | Enrolled: A: 29; B: 30
Analysed: A: 29; B: 30
Consecutive: NR
Age (years), mean (SD): A: 67 (10); B: 66 (10)
Sex, n (%): A: M 25 (86), F 4 (14); B: M 23 (77), F 7 (23)
Primary/previously treated patients: NR
Baseline contracture: mean (SD): A: 40° (12°); B: 37° (20°)
Inclusion criteria: NR
Exclusion criteria: NR | A: Collagenase injection: 0.25 ml for MCP joint contracture and 0.20 ml for PIP joint contracture. Patients returned the next day for manipulation of the contracted digit after local anaesthetic block. Repeat collagenase injections were offered if the desired reduction of contracture was not met at 4 weeks. There was no requirement to continue treatment until a specific contracture correction was achieved as described in the Collagenase Option for the Reduction of Dupuytren (CORD) studies
B: PNF: The hand was sterilely prepped and injected with subdermal lidocaine without adrenaline. Palpable and visible cords were released with 25- and 22-gauge needles. Patients actively flexed and extended the fingers to ensure the flexor tendons were not penetrated. After needle release along multiple sites of the cord, the finger was manipulated with gentle, progressive extension force. A digital block was performed before manipulation | Reduction of contracture, recurrence, adverse events |
| Case series studies |
First author, year: Badalamente 200048
Secondary reports:
Language: English
Publication type: full text
Number of centres: NR
Setting: orthopaedic department
Country: USA
Start/end dates:
Prospective/retrospective data collection: prospective
Study design: case series
Length of follow-up: mean MCP joints: 20 months; PIP joints: 14.1 months
Source of funding: NR | Enrolled: 35
Analysed: 34
Consecutive: no
Age (years), mean (SD): 64.8 (11.0)
Sex, n (%): M 32 (91.4), F 3 (8.6)
Primary/previously treated patients: NR
Baseline contracture: mean (SD) 49 (11); MCP 42 (13); PIP 52 (16)
Inclusion criteria: Dupuytren’s patients
Exclusion criteria: NR | A: The first study patient received a 300-U collagenase injection into the cord, that was causing MCP joint contracture. This failed to cause cord rupture and a dose escalation protocol was then used. The next 5 patients received 600, 1200, 2400, 4800 and 9600 units of collagenase, respectively, injected into the cord that was causing contracture of the MCP joints. One patient who had no benefit in the dose escalation study entered the following phase of the study. The remaining 29 patients, had collagenase injections at a dose level of 10,000 U (delivered in 0.25 ml for MCP joints and 0.20 ml for PIP joints) followed by a 10- to 12-hour period of hand immobilisation in a soft bulky gauze dressing. After this period there was no further immobilisation. If cord rupture did not occur on the day after the injection, the patients were instructed to apply extension force themselves. On the day after the injection the patients were fitted with a night extension splint that was worn for 4 months. All patients were instructed to do extension exercises at home. Daily vitamin E massage for 4 months was suggested | Reduction of contracture, recurrence, adverse events, time to correction |
First author, year: Badalamente 201177 (see entry for Hurst 2009 for details of the multicentre primary RCT)
Secondary reports:
Language: English
Publication type: abstract
Number of centres: 17
Setting: Multiple hospital sites
Country: USA
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: case series (follow-up of collagenase-treated patients only from one single-centre and one multicentre Phase III, double-blind, placebo controlled trials)
Length of follow-up: 3–5 years (mean 3.9 years)
Source of funding: Biospecifics Technologies Corp. and Auxilium Pharmaceuticals Inc. | Enrolled: 509
Analysed: 509
Consecutive: NR
Age (years), mean: single centre 61; multicentre 65
Sex, n (%): M 428 (84), F 81 (16)
Primary/previously treated patients: Both
Baseline contracture: NR
Inclusion criteria: NR
Exclusion criteria: NR | A: Collagenase clostridium histolyticum, 0.58 mg per injection, (0.25 ml MCP joints or 0.20 ml PIP joints) | Recurrence |
First author, year: Coleman 201278
Secondary reports:
Language: English
Publication type: full text
Number of centres: 1
Setting: hand and upper limb clinic
Country: Australia
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: case series
Length of follow-up: 30 or 90 days
Source of funding: Auxilium Pharmaceuticals | Enrolled: 12
Analysed: 12
Consecutive: NR
Age (years), mean (SD): 63.7 (5.5)
Sex, n (%): M 11 (92), F 1 (8)
Primary/previously treated patients: both
Baseline contracture: MCP joints ≤ 50° n = 5; PIP joints ≤ 40° n = 3, ≥ 40° n = 4
Inclusion criteria: general good health, age ≥ 18 and ≤ 70 years, diagnosis of DC with at least three fixed-flexion contractures, caused by palpable cords, that were ≥ 20 in PIP and/or MCP joints in fingers (not the thumbs), unable to simultaneously place the affected finger(s) and palm flat against a table top
Exclusion criteria: previous treatment of the selected joints within 90 days of first dose of study drug; chronic muscular, neurological, or neuromuscular disorders affecting the hands; known allergy to collagenase; collagenase treatment or treatment with any investigational drug within 30 days of first dose of study drug; anticoagulant within 7 days of first dose of study drug (with the exception of low-dose aspirin or NSAIDs); breastfeeding or pregnancy; and known history of stroke, bleeding disorder, or other medical condition that in the opinion of the investigator would compromise the subjects’ safety or the study objectives | A: single injection of collagenase (0.58 mg; volume of 0.25 ml for MCP joints and 0.20 ml for PIP joints) into a single cord. A finger extension procedure was conducted within 24 hours post-dosing. Patients were bandaged for the first few days following the finger extension procedure and then were fitted for a splint to be worn each night for up to 4 months
The same participants entered a second treatment period 30 days later, where two different affected joints on the same hand were treated during the same visit (i.e. patients received two concurrent 0.58-mg CCH doses) | Reduction of contracture, adverse events |
First author, year: Coleman 201479
Secondary reports:
Language: English
Publication type: full text
Number of centres: 8
Setting: hand and upper limb clinic
Country: Australia
Start/end dates: September 2011 to February 2012
Prospective/retrospective data collection: prospective
Study design: case series
Length of follow-up: 60 days
Source of funding: Auxilium Pharmaceuticals | Enrolled: 60
Analysed: 60
Consecutive: NR
Age (years), mean (SD): 64 (11)
Sex, n (%): M 51 (85), F 9 (15)
Primary/previously treated patients: both
Baseline contracture: all MCP joints (n = 75): 41 (17); all PIP joints (n = 45): 49 (19)
Inclusion criteria: 18 years or older, diagnosis of Dupuytren disease with at least two flexion contractures on the same hand that were 20° or greater in MCP and/or PIP joints in fingers (not thumbs) caused by palpable cords suitable for treatment, and a positive table top test
Exclusion criteria: | A: on day 1, finger goniometry was performed on joints to be treated and was followed by two concurrent injections of 0.58 mg CCH into cords affecting two joints in the same hand. A finger extension procedure was performed approximately 24 hours after administration of CCH in patients who did not have spontaneous disruption of the cord. Patients were fitted with an orthosis to be worn at night for up to 4 months and were instructed on how to perform a series of finger flexion–extension exercises at home. Follow-up visits to assess efficacy and safety occurred on days 8, 30 and 60. On completion of the day-60 visit, patients who required additional treatment in the treated hand could receive up to three additional injections of CCH (given as single injections 30 days apart). Patients could receive up to a total of five injections, and individual cords could receive up to a total of three injections | Change in joint contracture and ROM at 30 days; patient ratings of treatment satisfaction; physician ratings of improvement; clinical success rates (i.e. flexion contracture ≤ 5°) |
First author, year: Considine 201380
Secondary reports:
Language: English
Publication type: abstract
Number of centres: NR
Setting: outpatient clinic
Country: NR
Start/end dates: NR
Prospective/retrospective data collection: NR
Study design: case series
Length of follow-up: mean 4 days
Source of funding: NR | Enrolled: 10
Analysed: 10
Consecutive: NR
Age (years), mean: 66
Sex: NR
Primary/previously treated patients: both
Baseline contracture: mean MCP joints: 58.6°; PIP joints 39°
Inclusion criteria: patients waiting for fasciectomy for DC
Exclusion criteria: NR | A: collagenase injection and subsequent Dupuytren’s release performed in outpatient clinic. No anaesthetic was used. Patients were dressed with a bulky bandage and seen in the outpatients 48 hours later. Regional anaesthesia was administered using 10 ml of 0.5% bupivacaine hydrochloride (Marcaine, Hospira) to block the median and ulnar nerves at the wrist. An extension procedure was performed, and if skin tears developed the patients were dressed appropriately. Therapy was performed as for patients that had undergone Dupuytren’s fasciectomy | Reduction of contracture, adverse events |
First author, year: Hayton 201381
Secondary reports:
Language: English
Publication type: full text
Number of centres: 30 (16 CORD, 14 JOINT)
Setting: multiple hospital sites
Country: USA
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: case series
Length of follow-up: NR
Source of funding: Auxilium, Pfizer | Enrolled: 616
Randomised: N/A
Analysed: 616
Consecutive: NR
Age (years), mean (SD): 63 (10)
Sex, n (%): M 508 (83), F 108 (17)
Primary/previously treated patients: both
Baseline contracture: FFC, mean (SD), °:
Group A: 48.2 (20.2)
Group B: 49.7 (18.5)
Inclusion criteria: ≥ 1 PIP joint contracture at study entry and received ≥ 1 CCH injection during the study
Exclusion criteria: NR | A: For this secondary analysis, two patient subgroups were analysed to evaluate the direct and indirect effects of CCH on PIP joint contracture | Reduction of contracture, improvement in contracture, change in fixed-flexion contracture and ROM, adverse events |
First author, year: Kaplan 201383
Secondary reports:
Language: English
Publication type: abstract
Number of centres: NR
Setting: NR
Country: USA
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: RCT (treated as case series data for the purpose of this review)
Length of follow-up: 90 days
Source of funding: Auxilium Pharmaceuticals | Enrolled: NR
Randomised: NR
Analysed: 37
Consecutive: Yes
Age (years): NR
Sex: NR
Primary/previously treated patients: NR
Baseline contracture: NR
Inclusion criteria: DC involving the MCP joint > 20° caused by a palpable cord
Exclusion criteria: NR | A: all patients received 1 dose of collagenase (0.58 mg) and were observed for 90 days. Manipulation for cord rupture was performed at 1 (GROUP 1), 2 (GROUP 2) or 4 (GROUP 3) days after injection | Reduction of contracture, adverse events |
First author, year: Martin-Ferrero 201384
Secondary reports:
Language: English
Publication type: full text
Number of centres: 1
Setting: hospital outpatient clinic
Country: Spain
Start/end dates: 2011 to 2013
Prospective/retrospective data collection: prospective
Study design: case series
Length of follow-up: 1 year
Source of funding: NR | Enrolled: 35
Analysed: 35
Consecutive: NR
Age (years): 68 (range 45–89)
Sex: M 35/35 (100%)
Primary/previously treated patients: both
Baseline contracture: mean, MCP 64°; PIP 83°
Inclusion criteria: adults over 60 years (except where patient requested this treatment), Dupuytren’s disease, with a palpable band in at least 1 finger, excluding the thumb, and contraction of at least 20–90° at the MCP and 80° at the PIP
Exclusion criteria: patients with haemorrhagic disorders or recent stroke, with other neuromuscular hand disorders, patients who had received treatment including surgery for DC in the previous 90 days, allergy to collagenase or excipients, use of doxycycline in the previous 14 days and anticoagulant drugs in the previous 7 days | A: collagenase was administered by local injection directly into the palpable band, taking into account the specific doses necessary of both collagenase and solvent, depending on the joints to be treated according to the recommendations of the product. EMLA (numbing cream) (AstraZeneca) was topically administered in the injection area, half an hour earlier in an outpatient surgery room. After the injection, a compression bandage was applied and patients recommended to avoid movement. Extension of the finger and breakage of the band took place after 24 hours in an outpatient operating room, with local anaesthesia or sedation and subsequent compressive bandaging of the hand. Follow-up consultations were at 1 week, 2 weeks, 1 month, 3 months, 6 months and 1 year | Local complications, decrease of joint contracture, increase of range of motion |
First author, year: McMahon 201385
Secondary reports:
Language: English
Publication type: full text
Number of centres: 1
Setting: hand, wrist, arm, elbow and shoulder centre
Country: USA
Start/end dates: June 2010 to June 2012
Prospective/retrospective data collection: retrospective chart review with prospective patient recall
Study design: case series (chart review)
Length of follow-up: mean 15 months
Source of funding: NR | Enrolled: 102
Analysed: 48
Consecutive: NR
Age (years), mean: 66
Sex, n (%): M 31 (65), F 17 (35)
Primary/previously treated patients: NR
Baseline contracture: mean (SD), 48° (21°)
Inclusion criteria: at least 18 years of age at time of injection and minimum of 6 months between injection and research query
Exclusion criteria: patients who were enrolled in a separate study that involved a regimented hand therapy programme for severe PIP joint contractures were excluded | A: CCH injection administered by one of seven different board-certified hand surgeons and 24 digital manipulation and cord rupture 24 hours later. Digital block with 1–2% lidocaine hydrochloride (Xylocaine, AstraZeneca) was used just prior to digit manipulation to obtain pain relief. Patients then referred to a hand therapist, who fitted them with a customised thermoplastic dorsal- or volar-based orthosis and provided home therapy exercise education. All patients who met the inclusion criteria were then asked to return to the clinic to have their finger contractures measured. One observer collected the degree of passive contracture using a finger goniometer | Reduction of contracture, recurrence, adverse events, health-related quality of life, additional interventions required, patient satisfaction |
First author, year: Peimer 201386
Secondary reports:
Language: English
Publication type: full text
Number of centres: 10
Setting: community and academic centres
Country: USA
Start/end dates: January to February 2011
Prospective/retrospective data collection: retrospective
Study design: case series (chart review)
Length of follow-up: NR
Source of funding: Auxilium Pharmaceuticals | Enrolled: 501
Analysed: 463
Consecutive: NR
Age (years), mean (SD), range: 65.5 (10.1), 23–89
Sex, n (%): M 343 (74), F 120 (26)
Primary/previously treated patients: NR
Baseline contracture: mean (SD) = total: 49° (21°); MCP joints: 44° (20°); PIP joints 57° (21°)
Inclusion criteria: non-pregnant adult patients whose first collagenase injection was administered after 2 February 2010, the date of FDA approval, but before 31 December 2010
Exclusion criteria: NR | A: collagenase injection | Reduction of contracture, ROM, adverse events |
First author, year: Peimer 201387 (CORDLESS)
Secondary reports: Kaplan 2012
Language: English
Publication type: full text
Number of centres: NR
Setting: NR
Country: USA
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: case series [long-term follow-up of patients who received 1 or more CCH injections in their study of origin (i.e. JOINT I, JOINT II, CORD I, CORD I extension, or CORD II) and who had 1 or more post-treatment assessments]
Length of follow-up: 3 years (interim data)
Source of funding: Auxilium Pharmaceuticals | Enrolled: 643 (from 950 enrolled in the original studies)
Analysed: 643
Consecutive: NR
Age (years), mean (SD): 66 (9.4)
Sex, n (%): M 542 (84), F 101 (16)
Primary/previously treated: all previously treated
Baseline contracture: NR
Inclusion criteria: participation in any of the previous studies: two 9-month, open-label CCH trials (JOINT I and JOINT II); two 12-month, double-blind trials (CORD I and CORD II); and 1 open-label extension (CORD I extension). For inclusion in the previous study, see entry for Hurst 2009 above
Exclusion criteria: see entry for Hurst 2009 above | A: a single injection of 0.58 mg of CCH into the cord followed by a finger extension the next day, with 30 days of follow-up. An individual cord could receive a maximum of three CCH injection cycles to achieve the primary end point of success (FFC ≤ 5°), but if patients had multiple fingers involved, they could not receive more than eight total injections
CORDLESS patients are being observed once per calendar year for 4 years (year 2–5 after the first injection) with 6 or more months between consecutive visits | Recurrence, adverse events, worsening of contracture, progression |
First author, year: Skirven 201388
Secondary reports:
Language: English
Publication type: full text
Number of centres: NR
Setting: NR
Country: USA
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: case series
Length of follow-up: 4 weeks
Source of funding: Auxilium Pharmaceuticals | Enrolled: 21
Analysed: 21
Consecutive: no
Age (years), mean (range): 63 (37–80)
Sex, n (%): M 19 (90), F 2 (10)
Primary/previously treated patients: both
Baseline contracture: mean (range) passive PIP joint contracture: 56° (40–80°)
Inclusion criteria: PIP joints contracted at least 40°
Exclusion criteria: any patient with a passive contracture of < 40° was excluded | A: collagenase injection followed by digital manipulation to rupture the cord. 1 week following manipulation, a custom-fabricated, finger-based cylinder PIP joint orthosis in maximum extension was made and provided for daytime use for 4–6 weeks. This cylinder orthosis was used continuously during the day and removed only for exercises and hygiene. The hand-based extension orthosis was continued at night for 6 months following the injection | Reduction of contracture, adverse events |
First author, year: Syed 201391
Secondary reports:
Language: English
Publication type: full text
Number of centres: 1
Setting: trauma and orthopaedic department
Country: UK
Start/end dates: NR
Prospective/retrospective data collection: prospective
Study design: case series
Length of follow-up: 12 months
Source of funding: NR | Enrolled: NR
Analysed: 56
Consecutive: NR
Age (years), mean: 65
Sex, n (%): M 48 (86), F 8 (16)
Primary/previously treated patients: primary only
Baseline contracture: mean (SD) 41.8° (9.7°)
Inclusion criteria: Aged ≥ 18 years, in good general health, a single or spiral palpable cord AND involvement of a single MCP joint only AND moderate contracture severity (i.e. 30–60°)
Exclusion criteria: NR | A: collagenase injection (dose of 0.58 mg per injection). When the patient returned for the manipulation, an injection of 10 ml of 0.5% Marcaine was infiltrated around the CCH injection site 10 minutes prior to a controlled manual passive manipulation of the finger to full extension. No repeat collagenase injections or manipulations were performed | Reduction of contracture, recurrence, adverse events, health-related quality of life |
First author, year: Watt 201089
Secondary reports: Badalamente 200264
Language: English
Publication type: full text
Number of centres: 1
Setting: medical centre
Country: USA
Start/end dates: 1999 to 2000 (treatment dates)
Prospective/retrospective data collection: prospective
Study design: case series
Length of follow-up: 8 years
Source of funding: Auxilium Pharmaceuticals | Enrolled: 23
Analysed: 8
Consecutive: NR
Age (years), mean: 69 (range 52–86); MCP mean 67 (range 52–70); PIP mean 82 (range 77–86)
Sex: NR
Primary/previously treated patients: all previously treated
Baseline contracture: MCP 57 (range 30–76); PIP 45 (range 35–75)
Inclusion criteria: participated in collagenase arm of the Phase II RCT
Exclusion criteria: participants who did not receive collagenase | A: review of original records and abstraction of the initial degree of contracture, response to injection and dose response to injection. Participants returned for 8-year follow-up examination, which was performed by an independent examiner who had not been involved in the Phase II clinical trial. The examiner was blinded to the original location of injection. Goniometric measurements were obtained at both the MCP and PIP joint level of the index through little fingers of both hands and were expressed as degree of extensor lag. Subjects then completed a Dupuytren’s disease questionnaire which confirmed basic clinical history, including age at diagnosis, family history and prior treatment, including surgical fasciectomy, PNA and therapy. Participants answered questions related to disease recurrence and progression and were asked to judge the overall clinical success of the collagenase injection | Average contracture, recurrence |
First author, year: Witthaut 201390 (JOINT I, JOINT II)
Secondary reports: some participants also participated in the Peimer 201387 CORDLESS study
Language: English
Publication type: full text
Number of centres: 34
Setting: Multiple hospital departments
Country: USA (JOINT I); Australia, UK, Switzerland, Sweden, Denmark and Finland (JOINT II)
Start/end dates: September 2007 to December 2008
Prospective/retrospective data collection: prospective
Study design: case series
Length of follow-up: 9 months
Source of funding: Auxilium Pharmaceuticals | Enrolled: 587
Analysed: 587
Consecutive: NR
Age (years), mean (SD), range: JOINT I: 64.7 (9.9), 39–87; JOINT II: 63.2 (9.6), 35–86
Sex, n (%): JOINT I: M 164 (82), F 37 (18); JOINT II: M 334 (87), F 52 (13)
Primary/previously treated patients: both
Baseline contracture: mean (SD) JOINT I: 132.5 (109.8); JOINT II: 136.5 (104.2)
Inclusion criteria: aged ≥ 18 years, DC with a fixed-flexion deformity ≥ 20° and ≤ 100° (MCP joints) and ≥ 20° and ≤ 80° (PIP joints) in at least one finger other than the thumb that was caused by a palpable cord
Exclusion criteria: previous treatment, including surgery, for DC in the past 90 days; other muscular, neurological, or neuromuscular disorders affecting the hands; allergic to collagenase; pregnancy; history of stroke or bleeding or recent anticoagulant use; received doxycycline in the past 14 days | A: patients could receive up to five collagenase injections (five treatment cycles) with a maximum of three per cord, separated by at least 30 days. Only one cord could be injected within a given treatment cycle. The investigator prioritised the joints to be treated. A treatment cycle consisted of one 0.58-mg injection (0.25 ml MCP joints; 0.20 ml PIP joints. Patients underwent a standardised finger extension procedure to facilitate cord disruption on day 1 if a spontaneous disruption had not occurred. Patients were instructed to wear a splint at night for up to 4 months but otherwise to return to normal activities and perform finger flexion-extension exercises at home. The decision to reinject a cord that did not achieve correction to within 0–5° of normal was subject to patient or physician preference at day 30 | Reduction of contracture, ROM, adverse events |
