PrEvention of posttraumatic joint contractuRes with Ketotifen 2 (PERK 2)


Injured joints, especially the elbow, are at risk for permanent motion loss, also known as joint contractures. Joint contractures limit the function of a person due to the loss of elbow motion. For example, loss of elbow motion makes it difficult to perform activities of daily living such as feeding yourself, personal hygiene and dressing. Joint contractures are a recognized complication that occurs often after a fracture or dislocation of a joint. Current research suggests that mast cells, which are found in the joint, are key in causing the joint contracture. Mast cells are produced by our bone marrow along with other white blood cells and live in our tissues. They participate in healing after injury but in joint contractures they are over active. Research has been performed using a medication called Ketotifen. Ketotifen has been linked to stabilizing the mast cells and preventing the joint contracture. It is hoped that short-term use of this medication (Ketotifen) after a fracture or dislocation will prevent the contracture from occurring. This medication is not new. It is currently used in the treatment of Asthma. This research is continuing from another clinical study on people with elbow fractures or dislocations done in Calgary, Alberta Canada.

Impact Statement: Ketotifen is a mast cell stabilizer that prevents the release of growth factors and has been used for the treatment of asthma for over 40 years. It has a wide safety profile; there are no reported deaths from overdose, the side effects are minor with the most common side effects being transient sedation (14% of individuals) and 1 – 2 kg weight gain (0.9% of individuals), it does not impair fracture healing, and there are no known teratogenic events. It has been off patent for several years and is low cost. Ketotifen is an oral medication and easily stored and transported. Based on a review of the literature, and our preclinical and Phase II randomized clinical trial (RCT) comparing ketotifen to a placebo, ketotifen is the only pharmaceutical possibility available in the foreseeable future. Successful results using ketotifen to prevent post-traumatic elbow contractures can be rapidly translated to clinical care since it is Health Canada approved for human use. An application to Health Canada to include joint contracture prevention or treatment as another approved indication for ketotifen treatment is all that would be needed.
Post-traumatic joint contractures are a major issue. An analysis of the Calgary Health Region database revealed that approximately 1200 elbow fractures or dislocations occurred in 2002–2005. Most of the affected individuals were in the 20–60 year age group with an equal representation of men and women. Elbow injuries and their complications have a significant on productivity, return to work or duty, and quality of life. Thus, preventing contractures after joint injuries is a worthwhile strategy.
In addition to preventing contractures, there are other potential applications of Ketotifen. For people with established elbow contractures, operations can be performed to improve motion. Ketotifen could be used as an adjunct to operative contracture release for established post-traumatic contractures, or contractures that develop following elective procedures for degenerative conditions, such as total knee replacement.


Currently recruiting participants: Yes

Eligible gender: Male, Female, Transgender, Other

Eligible ages: 18 to 90

Inclusion criteria:

Inclusion criteria:
• Age ≥ 18 years old; skeletally mature
• Distal humerus (AO/OTA type 13) and/or proximal ulna and/or proximal radius fractures (AO/OTA type 21) and/or elbow dislocations (open fractures with or without nerve injury may be included)
• Injury ≤ 10 days
• Operative treatment of the elbow fracture or dislocation
• Subject has negative urine pregnancy test

Exclusion criteria:

Exclusion criteria:
• Pre-existing elbow contracture
• Elbow arthritis (osteoarthritis, inflammatory arthritis, gout, or nonspecific monoarticular arthritis)
• Inability to mobilize elbow within 21 days of injury
• Bilateral elbow injury
• Concomitant musculoskeletal or visceral injuries that prevent post-operative elbow physiotherapy
• Prior injury or surgery to the affected elbow
• Total elbow replacement planned for operative treatment
• Oral hypoglycemic medications
• Lactose intolerance
• Severe renal impairment
• Severe hepatic impairment
• History of epilepsy
• Male or Female of reproductive age unwilling to use two effective methods of contraception
• Female who is pregnant or breast feeding
• Language or cognitive difficulties preventing questionnaire completion
• 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


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Principal investigator:

Kevin Hildebrand

Clinical trial: