Investigations of Mechanisms and Treatment in Post-traumatic Joint Contractures

NCT ID: NCT01902017

Last Updated: 2018-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2017-08-31

Brief Summary

Injured joints, especially at the elbow, are at risk for permanent motion loss, also known as joint contractures. Joint contractures limit the function of an elbow and are a recognized complication that occurs often after a traumatic injury. The benefits of early motion after injury has helped in preventing joint contractures but there are still several patients that develop debilitating joint contractures. Current research suggests that mast cells, which are found in the joint, are key in causing joint contractures. Research has been done using a medication called Ketotifen. Ketotifen has been linked to stabilizing mast cells and preventing the joint contracture. It is hoped that short-term use of this medication after an injury will prevent the contracture from occurring.

Detailed Description

Individuals ≥ 18 years old with isolated distal 1/3 humerus and/or proximal 1/3 ulna and/or proximal 1/3 radius fractures and/or elbow dislocations (open fractures with or without nerve injury may be included) and presented to Peter Lougheed Centre (PLC), Foothills Medical Center (FMC), or South Health Campus (SHC).

Participants were required to take Ketotifen 5mg by mouth twice a day for 6 weeks or placebo twice a day by mouth for 6 weeks. Neither the participant nor the physician knew if the participant was taking Ketotifen or placebo. Sometimes this type of injury requires surgery. This study invited both patients that do and do not require surgery to participate.

We took a sample of blood to measure tryptase (normally found in the body). We predicted people with high levels of tryptase were more likely to develop stiffening in the joint.

Participants were asked to return for follow up visits 2, 6, 12, 24, and 52 weeks after surgery or date of initial injury if surgery was not required. These visits were part of normal care for this type of injury.

At the visit participants were asked to do the following, some of which was not part of normal care.

At each visit: Range of motion of the elbow was assessed, DASH score was completed- form helping the research group understand the level of disability from this injury, X-rays until the fracture was considered healed (this was normal treatment), SF12 - questionnaire about how the patient was feeling and coping with their injury, Additional information was collected about how the injury was healing and weight was measured.

The participant was required to have physiotherapy which is normal treatment for this injury.

The participant was contacted by telephone at week 1, 3, 4 and 5 while taking the study medication. During these times:

The participant was asked about:

• any problems with the study medication
• any new conditions or concerns that have developed

The participant was reminded:

• of next visit
• to continue to take study drug as instructed

During these telephone contacts, if any problems were detected that could not be rectified or figured out during the telephone interview, then participant was asked to attend the Cast Clinic to see their doctor in person.

Conditions

Joint Contractures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Operative, Ketotifen

Ketotifen 5mg orally twice per day for 6 weeks.

Group Type: EXPERIMENTAL

Ketotifen

Intervention Type: DRUG

5 mg PO bid

Non-operative, Ketotifen

Ketotifen 5mg orally twice per day for 6 weeks.

Group Type: EXPERIMENTAL

Ketotifen

Intervention Type: DRUG

5 mg PO bid

Operative, Placebo

Placebo oral medication twice daily for 6 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

5 mg placebo PO bid

Non-operative, Placebo

Placebo oral medication twice daily for 6 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

5 mg placebo PO bid

Interventions

Ketotifen

5 mg PO bid

Intervention Type: DRUG

Placebo

5 mg placebo PO bid

Intervention Type: DRUG

Other Intervention Names

Zaditen; Lactose Placebo

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years old
• Isolated distal 1/3 humerus fractures
• Proximal 1/3 ulna fractures
• Proximal 1/3 radial fractures
• Elbow dislocations
• Open fractures with or without nerve injury
• Presentation to Peter Lougheed Centre (PLC), Foothills Medical Centre (FMC) or South Health Campus (SHC).

Exclusion Criteria

• Pre-existing elbow contracture
• Osteoarthritis of affected elbow
• Inflammatory arthritis of affected elbow
• Gout of affected elbow
• Nonspecific monoarticular arthritis of the affected elbow
• Inability to give informed consent due to irreversible cognitive disorder
• Inability to comply with post-operative physiotherapy
• Injury > 7 days at the time of presentation
• Inability to mobilize elbow injury within 2 weeks of injury or surgery
• Pregnancy
• Breast feeding
• Oral hypoglycemic medications
• History of epilepsy
• Lactose intolerance

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

American Society for Surgery of the Hand

OTHER

Sponsor Role: collaborator

Workers' Compensation Board, Alberta

OTHER

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Dr. Kevin Hildebrand

Orthopaedic Surgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kevin Hildebrand, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

Peter Lougheed Centre

Calgary, Alberta, Canada

Foothills Medical Centre

Calgary, Alberta, Canada

South Health Campus

Calgary, Alberta, Canada

Countries

Canada

References

Liu CS, Ademola A, Zhang M, Garven A, Kopka M, Salo PT, Hart DA, Befus AD, Hildebrand KA. Human serum mast cell tryptase levels in elbow fractures or dislocations and its association with injury severity. J Orthop Res. 2020 Sep;38(9):2015-2019. doi: 10.1002/jor.24642. Epub 2020 Mar 11.

Reference Type: BACKGROUND

PMID: 32112583 (View on PubMed)

Hildebrand KA, Schneider PS, Mohtadi NGH, Ademola A, White NJ, Garven A, Walker REA, Sajobi TT; PERK 1 Investigators. PrEvention of Posttraumatic contractuRes with Ketotifen 1 (PERK 1): A Randomized Clinical Trial. J Orthop Trauma. 2020 Dec 1;34(12):e442-e448. doi: 10.1097/BOT.0000000000001878.

Reference Type: DERIVED

PMID: 32639394 (View on PubMed)

Other Identifiers

REB15-0081

Identifier Type: OTHER

Identifier Source: secondary_id

REB15-0081

Identifier Type: -

Identifier Source: org_study_id