Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

PrEvention of Posttraumatic Joint contractuRes With Ketotifen 2 (PERK2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03582176
Recruitment Status : Recruiting
First Posted : July 10, 2018
Last Update Posted : January 2, 2020
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Dr. Kevin Hildebrand, 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.

Condition or disease Intervention/treatment Phase
Elbow Fracture Elbow Injury Elbow Dislocation Drug: Lactose Placebo Drug: Ketotifen Fumarate 2mg Drug: Ketotifen Fumarate 5mg Phase 3

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 7 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 ≤ 7 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; concomittant 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 702 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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)
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: PrEvention of Posttraumatic Joint contractuRes With Ketotifen 2
Actual Study Start Date : April 26, 2019
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Lactose Placebo
Lactose Placebo by mouth twice per day
Drug: Lactose Placebo
One capsule by mouth twice per day

Active Comparator: Ketotifen Fumarate - 2mg
Ketotifen Fumarate 2 mg by mouth twice per day
Drug: Ketotifen Fumarate 2mg
2 mg tablets (over-encapsulated into one capsule) by mouth twice per day

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

Active Comparator: Ketotifen Fumarate - 5mg
Ketotifen Fumarate 5 mg by mouth twice per day
Drug: Ketotifen Fumarate 2mg
2 mg tablets (over-encapsulated into one capsule) by mouth twice per day

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




Primary Outcome Measures :
  1. Elbow Extension-Flexion Arc of Motion [ Time Frame: 12 weeks post-randomization ]
    The change in range of motion between baseline and 12 weeks post-randomization


Secondary Outcome Measures :
  1. Range of Motion at other time points [ Time Frame: 6 weeks, 24 weeks, 52 weeks ]
    Elbow extension-flexion arc of motion, forearm pronation-supination arc

  2. Patient Reported Outcome Measures [ Time Frame: Enrolment - 52 weeks ]
    Disability of the Arm, Shoulder and Hand (DASH) The upper extremity scoring scale DASH is a validated tool for disorders of the elbow with a range from 0 (least disability) to 100 (most disability). Ten is the average score in the general population and the minimal clinically important difference (MCID) is 10. DASH contains 30 questions asking participants about their ability to perform activities and their symptoms. Each question ranges from 1 (no difficulty) to 5 (unable). There is also optional work and sports/performing arts modules.

  3. Patient Reported Outcome Measures [ Time Frame: Enrolment - 52 weeks ]
    Oxford Elbow Score (OES). The OES is a 12-item questionnaire that is a valid measure of the outcome of surgery of the elbow in English (UK). It's 3 unidimensional domains include elbow function, pain, and social-psychological and the values range from 0 (greatest severity) to 100 (least severity). The OES has been used in trauma populations and its MCID is 10 for the elbow function domain and 18 for the pain and social-psychological domains.

  4. Patient Reported Outcome Measures [ Time Frame: 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.

  5. Radiographs [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 ≤ 7 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03582176


Contacts
Layout table for location contacts
Contact: Gerardo Duque, MA 403-943-5556 Gerardo.duque@ucalgary.ca
Contact: Kevin A Hildebrand, MD, FRCSC 403-220-7282 hildebrk@ucalgary.ca

Locations
Show Show 17 study locations
Sponsors and Collaborators
University of Calgary
United States Department of Defense
Investigators
Layout table for investigator information
Principal Investigator: Kevin A Hildebrand, MD, FRCSC University of Calgary and Alberta Health Services

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Dr. Kevin Hildebrand, Professor Department of Surgery, Principal Investigator, University of Calgary
ClinicalTrials.gov Identifier: NCT03582176    
Other Study ID Numbers: PERK2_KAH
CDMRP-OR160026 ( Other Grant/Funding Number: United States Department of Defense )
First Posted: July 10, 2018    Key Record Dates
Last Update Posted: January 2, 2020
Last Verified: December 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Kevin Hildebrand, University of Calgary:
Acute elbow fractures and/or dislocations
Additional relevant MeSH terms:
Layout table for MeSH terms
Joint Dislocations
Contracture
Wounds and Injuries
Joint Diseases
Musculoskeletal Diseases
Muscular Diseases
Ketotifen
Antipruritics
Dermatologic Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Allergic Agents