Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03582176 |
| Other study ID # |
PERK2_KAH |
| Secondary ID |
CDMRP-OR160026 |
| Status |
Active, not recruiting |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
April 26, 2019 |
| Est. completion date |
December 29, 2025 |
Study information
| Verified date |
March 2024 |
| Source |
University of Calgary |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
