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Study to Evaluate Iovera®° in Adult Patients Undergoing Total Knee Arthroplasty

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: NCT04191031
Recruitment Status : Not yet recruiting
First Posted : December 9, 2019
Last Update Posted : July 27, 2020
Sponsor:
Information provided by (Responsible Party):
Pacira CryoTech, Inc., a wholly owned subsidiary of Pacira BioSciences, Inc.

Brief Summary:

Primary objective: The primary objective of this study is to evaluate either a) the postsurgical total opioid consumption or b) postsurgical pain control after presurgical iovera° treatment plus EXPAREL® and standardized multimodal therapy compared with presurgical sham iovera° treatment plus EXPAREL and standardized multimodal therapy in subjects undergoing primary unilateral total knee arthroplasty (TKA). A single primary objective, either a or b, will be declared by an unblinded Independent Review Committee (IRC) in an interim analysis after 30 randomized and treated subjects complete the Day 42 assessments. The primary objective not selected will be placed in the secondary objectives category.

Secondary objectives: The secondary objectives of this study are to compare postsurgical pain control or postsurgical total opioid consumption (whichever is not chosen as the primary objective), opioid-free status, physical function, sleep quality, and safety of presurgical iovera° treatment plus EXPAREL and standardized multimodal therapy with presurgical sham iovera° treatment plus EXPAREL and standardized multimodal therapy in subjects undergoing primary unilateral TKA


Condition or disease Intervention/treatment Phase
Post-Operative Pain Management Device: ioveraº Device: ioveraº sham Not Applicable

Detailed Description:

This is a multicenter, prospective, randomized, double blind, sham controlled study in adult subjects undergoing TKA.

Subjects will be screened no more than 60 days prior to TKA. During the screening visit, subjects will be assessed for past or present neurologic, cardiac, and general medical conditions that, in the opinion of the Investigator, would preclude them from study participation. No procedures other than the site's standard of care will be performed before signed informed consent is obtained. After the informed consent form (ICF) is signed, demographic information, medical and surgical history, concomitant medications/concurrent procedures information and vital signs will be collected. Assessment of the intended treatment areas, functional-ability assessments, a urine drug screen, and a urine pregnancy test (UPT) for women of childbearing potential will be conducted.

Randomization: initially 60 subjects will be randomized 1:1 (30 subjects per group) to one of two treatment groups.

Group 1: subjects will receive iovera° cryoneurolysis treatment of superficial genicular nerves (anterior femoral cutaneous nerve [AFCN] and infrapatellar branches of the saphenous nerve [ISN]) of the target knee

Group 2: subjects will receive sham iovera° treatment of superficial genicular nerves (AFCN and ISN) of the target knee

All subjects in all groups will also receive intraoperative local infiltration with EXPAREL and postoperative multimodal pain medications.

Based on the results of an interim analysis, a primary endpoint between a) the postsurgical total opioid consumption or b) postsurgical pain control will be chosen and additional subjects may be enrolled (up to an estimated target of 200 subjects in total)..

Subjects will be asked questions and/or be asked to fill forms as part of the following assessments: Numeric Rating Scale (NRS) to assess pain scores and sleep quality, functional (physical) ability tests to assess range of motions, and KOOS questionnaire to assess knee movement.

iovera° treatment or iovera° sham treatment (Day -15 [±7 days] prior to TKA). TKA surgery will be Day 1 and follow up will be up to Day 90. Therefore, subjects may participate in the study for up to 155 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-blind, Randomized, Sham-controlled Study Assessing Opioid Utilization, Postoperative Pain and Function in Subjects Undergoing Total Knee Arthroplasty Treated With Presurgical Iovera®° or Sham Iovera®° Cryoneurolysis and Postsurgical Multimodal Pain Regimen
Estimated Study Start Date : August 2020
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Knee Replacement

Arm Intervention/treatment
Experimental: Superficial Genicular Nerves
Subjects will receive iovera° cryoneurolysis treatment of superficial genicular nerves (anterior femoral cutaneous nerve [AFCN] and infrapatellar branches of the saphenous nerve [ISN]) of the target knee
Device: ioveraº
Cryoneurolysis

Sham Comparator: Sham Comparator
Subjects will receive sham iovera° treatment of superficial genicular nerves (AFCN and ISN) of the target knee
Device: ioveraº sham
ioveraº sham




Primary Outcome Measures :
  1. Total opioid consumption in oral morphine equivalent dose from TKA (Day 1) to Day 42 (6 weeks post-TKA) [ Time Frame: Day 1 to Day 42 ]

Secondary Outcome Measures :
  1. The area under the curve (AUC) of the Numeric Rating Scale (NRS) "worst pain" intensity scores from TKA (Day 1) to Day 42 (6 weeks post-TKA) [ Time Frame: Day 1 to Day 42 ]
    NRS scale is 0 to 10 with 0 being no pain and 10 being the worst pain

  2. Numeric Rating Scale (NRS) pain intensity scores "right now" at Day 15, 30, 42, and Day 90 [ Time Frame: Day 15 to Day 90 ]
    NRS scale is 0 to 10 with 0 being no pain and 10 being the worst pain

  3. Numeric Rating Scale (NRS) pain intensity scores "average pain" at Day 4 to Day 42 [ Time Frame: Day 4 to Day 42 ]
    NRS scale is 0 to 10 with 0 being no pain and 10 being the worst pain

  4. Total opioid consumption in oral morphine equivalents from TKA-Day 15, TKA-Day 30, TKA-Day 42, and TKA-Day 90 [ Time Frame: Day 1 to Day 90 ]


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.


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Ages Eligible for Study:   22 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, at least 22 years of age at screening.
  2. Scheduled to undergo primary, unilateral, tricompartmental TKA under spinal anesthesia.
  3. Primary indication for TKA is degenerative osteoarthritis of the knee.
  4. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
  5. Anticipation of discharge to home after inpatient acute postop phase based on age, co-morbidities, home environment, and social support are in favor of discharge to home in the opinion of the Investigator.
  6. Females of childbearing potential must have a negative pregnancy test result prior to enrollment and agree to use a highly effective method of birth control during the study. A highly effective method of birth control is defined as one which results in a low failure rate (less than 1% per year).
  7. Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.

Exclusion Criteria:

  1. History of prior contralateral TKA within 6 months or open knee surgery on the knee being considered for TKA. Prior arthroscopy is permitted.
  2. Planned concurrent surgical procedure (e.g., bilateral TKA) or planned surgery within 90 days of study surgery.
  3. Undergoing unicompartmental TKA or revision TKA.
  4. Concurrent painful physical condition that may require analgesic treatment (such as an NSAID or opioid) in the postsurgical period for pain that is not strictly related to the knee surgery and which may confound the postsurgical assessments (e.g., significant pain from other joints including the non-index knee joint, chronic neuropathic pain, concurrent or prior contralateral TKA, concurrent foot surgery).
  5. Comorbidity that, in the judgment of the Investigator, may affect the subject's ability to participate in the study and postsurgical rehabilitation.
  6. Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications (i.e., bupivacaine, lidocaine, acetaminophen, tranexamic acid, celecoxib, naproxen, meloxicam).
  7. Use of any of the following medications within the times specified before TKA: long-acting and short-acting opioid medications within 6 weeks; or NSAIDs (except for low-dose aspirin used for cardioprotection) within 3 days or 5 elimination half-lives, whichever is longer.
  8. Initiation of treatment with any of the following medications within 1 month prior to the screening visit or ongoing concomitant use if the medication(s) are being given to control pain: selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), gabapentin, or duloxetine (Cymbalta®). If a subject is taking one of these medications for a reason other than pain control, he or she must be on a stable dose for at least 1 month prior to screening visit.
  9. Current use of systemic glucocorticosteroids within 1 month prior to screening in this study, intra-articular corticosteroid injections within 6 weeks, or Zilretta within 3 months.
  10. History of coronary or vascular stent placed within the past 6 months (may be extended to 1 year if medically indicated per physician discretion).
  11. Have been treated for a deep vein thrombosis, pulmonary embolism, myocardial infarction, or ischemic stroke within the past 6 months (may be extended to 1 year if medically indicated per physician discretion).
  12. Any clotting disorder and/or use of an anticoagulant (e.g., warfarin, clopidogrel, etc.) within seven (7) days prior to ioveraº treatment.
  13. Rheumatoid or inflammatory arthritis.
  14. History of severely impaired renal or hepatic function in the judgment of the investigator.
  15. Any neurologic or psychiatric disorder that might affect postsurgical pain or interfere with study assessments.
  16. Malignancy in the last 2 years, per physician discretion.
  17. History of misuse, abuse, or dependence on opioid analgesics, other prescription drugs, illicit drugs, or alcohol within the past 2 years.
  18. Use of medical marijuana within 6 weeks prior to screening visit or continuation thereafter.
  19. Body weight <50 kg (110 pounds) or a body mass index >40 kg/m2.
  20. Previous iovera° treatment.
  21. Greater than 15° malalignment (varus or valgus) on presurgical radiograph.
  22. Prior surgery in the treatment areas that may have altered the anatomy of nerves intended to be treated with the ioveraº system or result in scar tissue in the treatment area.
  23. Open and/or infected wounds at or near the treatment site.
  24. Any other local skin condition at the treatment sites that in the Investigator's judgment would adversely affect treatment or outcomes.
  25. History of cryoglobulinemia.
  26. History of paroxysmal cold hemoglobinuria.
  27. History of cold urticaria.
  28. History of Raynaud's disease.
  29. Administration of an investigational product within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to screening, or planned administration of another investigational product or procedure during the subject's participation in this study

Given the COVID-19 pandemic, the subject must be medically fit/cleared for surgery by the investigator. If there is a concern about a subject's recent or potential exposure to COVID-19, or if the subject is not medically fit/cleared for surgery due to suspected COVID-19 illness/symptoms (or other serious illness), the subject must be excluded per Exclusion criterion #5.


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): NCT04191031


Contacts
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Contact: Christine Brozyniak 973-254-4364 christine.brozyniak@pacira.com
Contact: Kim Hunsicker, MSN, CRNP, MBA 973-254-4361 Kim.Hunsicker@pacira.com

Sponsors and Collaborators
Pacira CryoTech, Inc., a wholly owned subsidiary of Pacira BioSciences, Inc.
Investigators
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Study Director: Nayana Nagaraj, MD, PhD, MPH Pacira Pharmaceuticals, Inc
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Responsible Party: Pacira CryoTech, Inc., a wholly owned subsidiary of Pacira BioSciences, Inc.
ClinicalTrials.gov Identifier: NCT04191031    
Other Study ID Numbers: IOV-401
First Posted: December 9, 2019    Key Record Dates
Last Update Posted: July 27, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations