PrEvention of Posttraumatic Joint contractuRes With Ketotifen 2

NCT ID: NCT03582176

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 395 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-26
• Study Completion Date: 2024-12-17

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.

Conditions

Elbow Fracture; Elbow Injury; Elbow Dislocation

Study Design

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

Study Groups

Lactose Placebo

Lactose Placebo by mouth twice per day

Group Type: PLACEBO_COMPARATOR

Lactose Placebo

Intervention Type: DRUG

One capsule by mouth twice per day

Ketotifen Fumarate - 2mg

Ketotifen Fumarate 2 mg by mouth twice per day

Group Type: ACTIVE_COMPARATOR

Ketotifen Fumarate 2mg

Intervention Type: DRUG

2 mg tablets (over-encapsulated into one capsule) by mouth twice per day

Ketotifen Fumarate 5mg

Intervention Type: DRUG

5 mg tablets (over-encapsulated into one capsule) by mouth twice per day

Ketotifen Fumarate - 5mg

Ketotifen Fumarate 5 mg by mouth twice per day

Group Type: ACTIVE_COMPARATOR

Ketotifen Fumarate 2mg

Intervention Type: DRUG

2 mg tablets (over-encapsulated into one capsule) by mouth twice per day

Ketotifen Fumarate 5mg

Intervention Type: DRUG

5 mg tablets (over-encapsulated into one capsule) by mouth twice per day

Interventions

Lactose Placebo

One capsule by mouth twice per day

Intervention Type: DRUG

Ketotifen Fumarate 2mg

2 mg tablets (over-encapsulated into one capsule) by mouth twice per day

Intervention Type: DRUG

Ketotifen Fumarate 5mg

5 mg tablets (over-encapsulated into one capsule) by mouth twice per day

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Dr. Kevin Hildebrand

Professor Department of Surgery, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kevin A Hildebrand, MD, FRCSC

Role: PRINCIPAL_INVESTIGATOR

University of Calgary and Alberta Health Services

Locations

Sturgeon Community Hospital

St. Albert, Alberta, Canada

University of Maryland Medical Centre

Baltimore, Maryland, United States

Carolinas Medical Center

Charlotte, North Carolina, United States

University of Vermont Medical Center

Burlington, Vermont, United States

Peter Lougheed Centre

Calgary, Alberta, Canada

Foothills Medical Centre

Calgary, Alberta, Canada

South Health Campus

Calgary, Alberta, Canada

Royal Columbia Hospital

New Westminster, British Columbia, Canada

St. Paul's Hospital

Vancouver, British Columbia, Canada

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

St. Joseph's Health Care London

London, Ontario, Canada

The Ottawa General Hospital

Ottawa, Ontario, Canada

The Ottawa Civic Hospital

Ottawa, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

Ademola A, Hildebrand KA, Schneider PS, Mohtadi NGH, White NJ, Bosse MJ, Garven A, Walker REA, Sajobi TT. PrEvention of posttraumatic contractuRes with Ketotifen 2 (PERK 2) - protocol for a multicenter randomized clinical trial. BMC Musculoskelet Disord. 2020 Feb 24;21(1):123. doi: 10.1186/s12891-020-3139-2.

Reference Type: DERIVED

PMID: 32093652 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CDMRP-OR160026

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PERK2_KAH

Identifier Type: -

Identifier Source: org_study_id