Clinical trial NCT03015532: Total Knee Arthroplasty Infiltration Study for Postoperative Analgesia
Official title: A Phase 2b, Randomized, Double-Blind, Saline Placebo- and Active-Controlled, Multicenter Study of HTX-011 Via Infiltration for Postoperative Analgesia in Subjects Undergoing Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postoperative Pain
Keywords: knee
knee replacement
arthroplasty
joint replacement
knee pain
Lead sponsor: Heron Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-01-10
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2b, randomized, double-blind, saline placebo- and active-controlled, multicenter study in subjects undergoing primary unilateral total knee arthroplasty (TKA) to evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of HTX-011 administered via infiltration to the surgical site.


Eligibility criteria: Inclusion Criteria:

* Is scheduled to undergo primary unilateral TKA under general anesthesia.
* Has not previously undergone TKA in either knee.
* Has an American Society of Anesthesiologists Physical Status of I, II, or III.
* Is able to demonstrate motor function by performing a timed 20-meter walk unassisted, but with the optional use of a 4-legged walker for balance.
* Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant during the study, sterile; or using acceptable contraceptives.

Exclusion Criteria:

* Has a planned concurrent surgical procedure (eg, bilateral TKA).
* Has a pre-existing concurrent acute or chronic painful/restrictive physical condition that may require analgesic treatment in the postoperative period for pain.
* Has a contraindication or a known or suspected history of hypersensitivity or idiosyncratic reaction to required study medications.
* Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months.
* Has taken NSAIDs within 10 days prior to the scheduled surgery.
* Has taken opioids within 24 hours prior to the scheduled surgery (3 days for long-acting).
* Has been administered bupivacaine within 5 days prior to the scheduled surgery.
* Has initiated treatment with medications within 1 month prior to study drug administration that can impact pain control.
* Has been administered systemic steroids within 5 half-lives or 10 days prior to administration of study drug.
* Has a medical condition such that, in the opinion of the Investigator, participating in the study would pose a health risk to the subject or confound the postoperative assessments.
* Has a known history of Hepatitis B, human immunodeficiency virus (HIV), or active Hepatitis C.
* Has uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments.
* Has any chronic neuromuscular deficit of either femoral nerve function or thigh musculature. Has any chronic condition or disease that would compromise neurological or vascular assessments.
* Had a malignancy in the last year, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
* Has a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse.
* Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives.
* Has undergone 3 or more surgeries within 12 months.
* Has a body mass index (BMI) \>38 kg/m2.

Primary outcomes:
measure: Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 48 Hours Postsurgery (AUC0-48).
timeFrame: 48 hours
Secondary outcomes:
measure: Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores at Rest (NRS-R) Through 72 Hours Postsurgery (AUC0-72).
timeFrame: 72 hours
measure: Mean Total Postoperative Opioid Consumption (in Morphine Equivalents)
timeFrame: 72 hours
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Sheffield
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Riverside
country: United States
state: California
city: San Diego
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Tamarac
country: United States
state: Florida
city: Las Vegas
country: United States
state: Nevada
city: Columbus
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Bellaire
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Webster
country: United States
state: Texas
Study officials:
References:
citation: Lachiewicz PF, Lee GC, Pollak RA, Leiman DG, Hu J, Sah AP. HTX-011 Reduced Pain and Opioid Use After Primary Total Knee Arthroplasty: Results of a Randomized Phase 2b Trial. J Arthroplasty. 2020 Oct;35(10):2843-2851. doi: 10.1016/j.arth.2020.05.044. Epub 2020 May 27.