PrEvention of Posttraumatic Joint contractuRes With Ketotifen 2
- Conditions
- Elbow FractureElbow InjuryElbow Dislocation
- Interventions
- Registration Number
- NCT03582176
- Lead Sponsor
- University of Calgary
- Brief Summary
PrEvention of posttraumatic contractuRes with Ketotifen 2 (PERK 2) is a Phase III randomized, controlled, double blinded multicenter trial with 3 parallel groups (Ketotifen 2 mg or 5 mg or lactose placebo twice daily orally for 6 weeks) and a primary endpoint of elbow extension-flexion range of motion (ROM) arc at 12 weeks post-randomization.
- Detailed Description
PrEvention of posttraumatic contractuRes with Ketotifen 2 (PERK2) is a Phase III randomized, controlled, double blinded multicenter trial with 3 parallel groups (Ketotifen 2 mg or 5 mg or lactose placebo twice daily orally for 6 weeks) and a primary endpoint of elbow extension-flexion range of motion (ROM) arc at 12 weeks post-randomization. The Research Hypothesis is that Ketotifen is superior to a lactose placebo in reducing joint contracture severity in adult participants with isolated elbow fractures or dislocations. The Primary Objective is to determine if Ketotifen given within 10 days of injury can reduce post-traumatic elbow joint contractures when compared to placebo. The Secondary Objectives are: 1) to ascertain the optimal dose of Ketotifen and 2) to compare adverse events in Ketotifen and placebo groups.
Inclusion criteria: age ≥ 18 years old and skeletally mature; distal humerus (AO/OTA type 13) and/or proximal ulna and/or proximal radius fractures (AO/OTA type 2U1/2R1) and/or elbow dislocations (open fractures with or without nerve injury may be included); injury ≤ 10 days; ability to give informed consent; able to comply with protocol and follow up; operative treatment of the elbow fracture or dislocation; participant has negative urine or blood serum pregnancy test.
Exclusion criteria: Pre-existing elbow contracture; elbow arthritis (osteoarthritis, inflammatory arthritis, or nonspecific monoarticular arthritis); inability to mobilize elbow within 21 days of injury; bilateral elbow injury; oral hypoglycemic medications; history of epilepsy; lactose intolerance; language or cognitive difficulties preventing completion of questionnaires; pregnancy; breast feeding; male or female unwilling to use 2 methods of contraception; total elbow replacement planned for treatment of fracture or dislocation; prior elbow injury or operation; concomitant musculoskeletal or visceral injuries preventing post-operative elbow therapy; severe renal and hepatic impairment.
Outcome Measures: Range of motion; Disability Arm, Shoulder, Hand; Oxford Elbow Score; Pain Catastrophizing Scale; standardized case report form; radiographic evaluation for fracture healing/non-union; and number of participants requiring reoperation for all elbow related causes, and post-traumatic joint contractures, 2 - 52 weeks post-randomization.
Safety Endpoints: The main safety endpoint for this study is the frequency of adverse events and serious adverse events, and radiographic assessment for non-union and heterotopic ossification (HO), 2 - 52 weeks post-randomization.
Ketotifen is the first and only agent demonstrating a significant decrease in contracture severity in preclinical trials that also has a wide safety profile. Ketotifen has been used in the treatment of chronic asthma for over 40 years in humans. Ketotifen is a medication that has anti-anaphylactic properties, due to the prevention of the synthesis and/or release of growth factors and mediators, as well as antihistamine affects due to H1 receptor antagonism. Post market surveillance has confirmed the safety of Ketotifen. A Phase II RCT comparing a single dose of Ketotifen (5 mg) to placebo in elbow fractures or dislocations in Calgary (ClinicalTrials.gov Identifier NCT01902017), demonstrated safety of Ketotifen and coupled with preclinical animal studies informed the need to increase the sample size, examine multiple doses, and narrow the study population to more severe injuries requiring an operation in the Phase III RCT.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 395
- Age ≥ 18 years old; skeletally mature with no growth plates in the elbow
- Distal humerus (AO/OTA type 13) and/or proximal ulna and/or proximal radius fractures (AO/OTA type 2U1 or 2R1) and/or elbow dislocations (open fractures with or without nerve injury may be included)
- Operative treatment of the elbow fracture or dislocation
- Injury ≤ 10 days
- Participant has a negative urine or blood serum pregnancy test
- Pre-existing elbow contracture
- Elbow arthritis (osteoarthritis, inflammatory arthritis, or nonspecific monoarticular arthritis)
- Inability to mobilize elbow within 21 days of injury
- Bilateral elbow injury
- Concomitant musculoskeletal or visceral injuries preventing post-operative elbow therapy
- Oral hypoglycemic medications
- History of epilepsy
- Lactose intolerance
- Language or Cognitive difficulties preventing reliable completion of questionnaires
- Females who are pregnant or breast feeding
- Females of reproductive age or males unwilling to use 2 effective methods of contraception
- Severe renal impairment
- Severe hepatic impairment
- Prior elbow injury or operation
- Total elbow replacement planned for treatment of injury
- Unlikely to maintain follow up (no fixed address, plans to move out of town in the next year, states unable to comply with protocol)
- Unwilling or unable to provide written informed consent for trial participation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lactose Placebo Lactose Placebo Lactose Placebo by mouth twice per day Ketotifen Fumarate - 2mg Ketotifen Fumarate 2mg Ketotifen Fumarate 2 mg by mouth twice per day Ketotifen Fumarate - 2mg Ketotifen Fumarate 5mg Ketotifen Fumarate 2 mg by mouth twice per day Ketotifen Fumarate - 5mg Ketotifen Fumarate 2mg Ketotifen Fumarate 5 mg by mouth twice per day Ketotifen Fumarate - 5mg Ketotifen Fumarate 5mg Ketotifen Fumarate 5 mg by mouth twice per day
- Primary Outcome Measures
Name Time Method Elbow Extension-Flexion Arc of Motion 12 weeks post-randomization The change in range of motion between baseline and 12 weeks post-randomization
- Secondary Outcome Measures
Name Time Method Range of Motion at other time points 6 weeks, 24 weeks, 52 weeks Elbow extension-flexion arc of motion, forearm pronation-supination arc
Patient Reported Outcome Measures Enrolment - 52 weeks Pain Catastrophizing Scale (PCS). The PCS is a 13-item instrument that can be completed in 5 minutes and requires a Grade 6 level of reading. For each question the participant has a choice from a range of 0 (not at all) to 4 (all the time). There are 3 subscale scores assessing rumination, magnification, and helplessness that are combined into an overall score. PCS total scores range from 0 - 52. Research at the University Centre for Research on Pain and Disability indicates that a total PCS score of 30 represents clinically relevant level of catastrophizing. It has been used in the assessment of injuries to the elbow, wrist, and hand where results are dependent on this behavior.
Radiographs Enrolment - 52 weeks Radiographic evaluation for fracture healing and/or nonunion, and the number of participants requiring re-operation for contracture and also composite re-operation for all elbow related causes. This will be completed by a radiologist.
Trial Locations
- Locations (15)
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
University of Maryland Medical Centre
🇺🇸Baltimore, Maryland, United States
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
The Ottawa Civic Hospital
🇨🇦Ottawa, Ontario, Canada
Peter Lougheed Centre
🇨🇦Calgary, Alberta, Canada
Sturgeon Community Hospital
🇨🇦St. Albert, Alberta, Canada
Royal Columbia Hospital
🇨🇦New Westminster, British Columbia, Canada
St. Joseph's Health Care London
🇨🇦London, Ontario, Canada
The Ottawa General Hospital
🇨🇦Ottawa, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
South Health Campus
🇨🇦Calgary, Alberta, Canada
Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada