Total Knee Arthroplasty (TKA) Study of HTX-011 in an Multimodal Analgesic Regimen (MMA) Regimen

Analgesia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03974932
• Other study ID #: HTX-011-306
• Status: Completed
• Phase: Phase 3
• Start date: June 5, 2019
• Est. completion date: January 7, 2021

Study information

• Verified date: August 2023
• Source: Heron Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: January 7, 2021
• Est. primary completion date: December 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Analgesia

Intervention

Drug:
• HTX-011
Dual-acting local anesthetic. Dose 1.
• Ibuprofen
NSAID.
• Acetaminophen
Analgesic.
• Celecoxib
NSAID.
• +/- Bupivacaine HCl
Local anesthetic.

Device:
• Luer Lock Applicator
Applicator for instillation.

Drug:
• HTX-011
Dual-acting local anesthetic. Dose 2.

Locations

Country	Name	City	State
United States	First Surgical Hospital	Bellaire	Texas
United States	Midwest Clinical Research Center, LLC	Dayton	Ohio
United States	Plano Surgical Hospital	Plano	Texas
United States	Endeavor Clinical Trials, LLC.	San Antonio	Texas
United States	Helen Keller Hospital	Sheffield	Alabama
United States	Phoenix Clinical Research, LLC	Tamarac	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Heron Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS).	The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line.	12 through 48 hours
Secondary	Mean AUC of VAS Scores.	The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line.	72 hours
Secondary	Mean AUC of the NRS of Pain Intensity at Rest (NRS-R).	Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents "no pain" and 10 represents "worst pain". NRS scores are measured at rest.	72 hours
Secondary	Percentage of Subjects With Severe Pain.	Severe Pain defined as a VAS score =7.5 cm.	24 hours, 48 hours, 72 hours
Secondary	Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]).		72 hours
Secondary	Percentage of Subjects Who Are Opioid-free		72 Hours to Day 11
Secondary	Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11.		72 hours through Day 11
Secondary	Median Time to First Opioid Rescue Medication.		Through 72 hours
Secondary	Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge.		72 hours
Secondary	Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit.		72 hours through Day 11
Secondary	Percentage of Subjects Achieving a Score of "Good" or Better (>1) Pain Control Based on Patient Global Assessment (PGA).	Patient's Global Assessment (PGA) of pain control is a 4-point scale in which subjects rate how well their pain has been controlled (0 = Poor; 1 = Fair; 2 = Good; 3 = Excellent).	24 hours, 48 hours, 72 hours, Day 11
Secondary	Median Time to First Ambulation Postsurgery.		72 hours
Secondary	Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain.		72 hours
Secondary	Percentage of Subjects Who First Achieve an MPADSS Score =9.	Subjects were assessed for readiness for discharge using the Modified Post-Anesthesia Discharge Scoring System (MPADSS) that assesses 5 clinical variables: vital signs, ambulation, nausea/vomiting, pain, and surgical bleeding, each on a 3-point scale of 0, 1, or 2 with 0 being the worst score and 2 being the best score. Subjects with an MPADSS score of 9 or 10 were considered ready for discharge.	2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24, hours, 36 hours, 48 hours, 60 hours, 72 hours
Secondary	Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility.	Number Analyzed represents Subjects who were discharged home.	72 hours
Secondary	Mean Overall Benefit of Analgesia Score (OBAS).	Subjects were questioned about their overall benefit of analgesia. Overall benefit of analgesia score (OBAS) assesses current pain at rest, vomiting, itching, sweating, freezing, dizziness, and overall satisfaction with postoperative pain during the previous 24 hours. To calculate the OBAS score, each of the subscale scores (0=minimum; 4=maximum) are summed for a combined OBAS score. Possible scores could range from 0 to 28 with a lower score indicating greater benefit.	24 hours, 48 hours, 72 hours, Day 11
Secondary	Mean Total TSQM-9 Score	The Treatment Satisfaction Questionnaire for Medication (TSQM-9) contains 9 items assessing Effectiveness, Convenience, and Global Satisfaction domains. Responses to items are rated on a 5-point or 7-point rating scale. Scores for each domain are computed by adding the TSQM items in each domain and then transforming the values in to a composite score ranging from 0 to 100, with higher scores representing higher satisfaction.	72 hours through Day 11
Secondary	Maximum Concentration (Cmax)		72 hours
Secondary	Time of Occurrence of Maximum Concentration (Tmax)		72 hours