Clinical trial NCT03974932: Total Knee Arthroplasty (TKA) Study of HTX-011 in an Multimodal Analgesic Regimen (MMA) Regimen
Official title: A Phase 3b, Open-Label Study of HTX-011 as Part of a Scheduled Non-Opioid Multimodal Analgesic Regimen in Subjects Undergoing Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Analgesia
Keywords: total knee arthroplasty
postoperative pain
multimodal analgesia
Lead sponsor: Heron Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-06-05
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase 3b, open-label single-arm study in which all subjects receive HTX-011 as part of a scheduled non-opioid MMA regimen.


Eligibility criteria: Inclusion Criteria:

* Is scheduled to undergo primary unilateral TKA under spinal anesthesia.
* Has not previously undergone TKA in either knee.
* Has an American Society of Anesthesiologists (ASA) Physical Status of I, II, or III.
* Is able to walk at least 20 feet with 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 is at least 2 years post-menopausal; or is in a monogamous relationship with a partner who is surgically sterile; or using acceptable contraceptives.

Exclusion Criteria:

* Has a planned concurrent surgical procedure.
* Has other pre-existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain.
* Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications.
* Using or expected to use Factor IX Complex or anti-inhibitor coagulant concentrates during the study.
* 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 with the exception of subjects on low-dose (≤100 mg) daily acetylsalicylic acid for cardioprotection.
* 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 been administered any local anesthetic within 72 hours 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.
* Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives.
* 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.
* 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.
* Is currently undergoing treatment for hepatitis B, hepatitis C, or HIV.
* Has uncontrolled anxiety, psychiatric, or neurological disorder that, in the opinion of the Investigator, might interfere with study assessments.
* Has acquired defective color vision or acute gastrointestinal ulcers, either of which could interfere with scheduled study medications.
* 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 nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
* Has undergone 3 or more surgeries within 12 months.
* Has a body mass index (BMI) \>39 kg/m2.

Primary outcomes:
measure: Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS).
timeFrame: 12 through 48 hours
Secondary outcomes:
measure: Mean AUC of VAS Scores.
timeFrame: 72 hours
measure: Mean AUC of the NRS of Pain Intensity at Rest (NRS-R).
timeFrame: 72 hours
measure: Percentage of Subjects With Severe Pain.
timeFrame: 24 hours, 48 hours, 72 hours
measure: Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]).
timeFrame: 72 hours
measure: Percentage of Subjects Who Are Opioid-free
timeFrame: 72 Hours to Day 11
measure: Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11.
timeFrame: 72 hours through Day 11
measure: Median Time to First Opioid Rescue Medication.
timeFrame: Through 72 hours
measure: Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge.
timeFrame: 72 hours
measure: Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit.
timeFrame: 72 hours through Day 11
measure: Percentage of Subjects Achieving a Score of "Good" or Better (>1) Pain Control Based on Patient Global Assessment (PGA).
timeFrame: 24 hours, 48 hours, 72 hours, Day 11
measure: Median Time to First Ambulation Postsurgery.
timeFrame: 72 hours
measure: Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain.
timeFrame: 72 hours
measure: Percentage of Subjects Who First Achieve an MPADSS Score ≥9.
timeFrame: 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24, hours, 36 hours, 48 hours, 60 hours, 72 hours
measure: Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility.
timeFrame: 72 hours
measure: Mean Overall Benefit of Analgesia Score (OBAS).
timeFrame: 24 hours, 48 hours, 72 hours, Day 11
measure: Mean Total TSQM-9 Score
timeFrame: 72 hours through Day 11
measure: Maximum Concentration (Cmax)
timeFrame: 72 hours
measure: Time of Occurrence of Maximum Concentration (Tmax)
timeFrame: 72 hours
Other outcomes:
Locations:
city: Sheffield
country: United States
facility: Helen Keller Hospital
state: Alabama
city: Tamarac
country: United States
facility: Phoenix Clinical Research, LLC
state: Florida
city: Dayton
country: United States
facility: Midwest Clinical Research Center, LLC
state: Ohio
city: Bellaire
country: United States
facility: First Surgical Hospital
state: Texas
city: Plano
country: United States
facility: Plano Surgical Hospital
state: Texas
city: San Antonio
country: United States
facility: Endeavor Clinical Trials, LLC.
state: Texas
Study officials:
References: