Study of Local Administration of DepoTXA for Reduced Postsurgical Bleeding in Subjects Undergoing TKA

NCT02922582 | Terminated Phase 2 Results

• 1 other identifier: 404-C-201
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase 2, randomized, single-blind, active-controlled dose-ranging study in subjects scheduled to undergo total knee arthroplasty (TKA).

Conditions

Total Knee Arthroplasty

Outcome Measures

Primary Outcomes (6)

• Area Under the Plasma Concentration-versus-time Curve From Time 0 Extrapolated to Infinity After Drug Administration

  Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.

• Area Under the Plasma Concentration-versus-time Curve From Time 0 to the Last Collection Time After Drug Administration

  Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.

• Maximum Plasma Concentration (Cmax)

  Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.

• Time to Maximum Plasma Concentration (Tmax)

  Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.

• The Apparent Terminal Elimination Rate Constant

  Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.

• The Apparent Terminal Elimination Half-life

  Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.

Secondary Outcomes (7)

• Summary of Neurological Assessments (Proportion of Subjects Who Were Oriented and Proportion of Subjects Who Had Any of the Neurologic Events) at Each Assessed Timepoint

  12, 24, 36, 48, 60, 72, and 96 hours after study drug administration

• Incidence of Reoperation Due to Hematoma or Wound Dehiscence

  Through day 60

• Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused)

  Day 60

• Number of Participants With 90˚ Passive and Active Knee Flexion

  24, 48, and 72 hours

• Time to Complete Timed Up-and-Go (TUG) Test

  Day 1; at approximately 8:00 am and 8:00 pm (±2 hours) daily from Day 2 through hospital discharge; and on Day 7

Study Arms (4)

DepoTXA 400mg

EXPERIMENTAL

400mg Intracapsular at the end of surgery one time

Drug: DepoTXA

DepoTXA 800mg

EXPERIMENTAL

800mg Intracapsular at the end of surgery one time

Drug: DepoTXA

DepoTXA 1200mg

EXPERIMENTAL

1200mg Intracapsular at the end of surgery one time

Drug: DepoTXA

IV Tranexamic acid (TXA)

ACTIVE COMPARATOR

1 g of IV TXA at the end of surgery

Drug: Tranexamic Acid

Interventions

DepoTXA DRUG

DepoTXA 1200mg; DepoTXA 400mg; DepoTXA 800mg

Tranexamic Acid DRUG

IV Tranexamic acid (TXA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, ≥18 years of age at screening.
• Scheduled to undergo elective unilateral open TKA under general, spinal, or regional anesthesia.
• American Society of Anesthesiology (ASA) physical status 1, 2, or 3.
• Female subject must be surgically sterile; or at least 2 years postmenopausal; or have a monogamous partner who is surgically sterile; or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, or transdermal, contraceptive approved by the FDA for greater than 2 months prior to screening and commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study.
• Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.

You may not qualify if:

• Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.
• Planned concurrent surgical procedure (e.g., bilateral TKA).
• Prior open knee surgery on ipsilateral knee. Prior arthroscopy is permitted.
• Subjects taking a medication with a known procoagulant effect (e.g., combination hormonal contraceptives, Factor IX complex concentrates or anti-inhibitor coagulant concentrates, or all-trans retinoic acid).
• Contraindication or hypersensitivity to TXA.
• History of thrombosis or prior Venous thromboembolism (VTE).
• Known coagulopathy or active intravascular clotting.
• Prior myocardial infarction.
• Prior cardiovascular accident (stroke) or subarachnoid hemorrhage.
• History of epilepsy.
• Presence of an intravascular stent.
• History of impaired kidney function, chronic respiratory disease, rheumatoid arthritis, coagulopathy, or loss of sensation in extremities.
• Renal insufficiency (serum creatinine level \>2 mg/dL).
• Anemia (Hb level \<10 g/dL).
• Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments.

Sponsors & Collaborators

• Pacira Pharmaceuticals, Inc: lead

Study Sites (5)

Ortho Arizona

Gilbert, Arizona, 85296, United States

Location

University of Miami Hospital

Miami, Florida, 33136, United States

Location

Kendall Regional Medical Center

Miami, Florida, 33175, United States

Location

Ohio State University/Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Interventions

Tranexamic Acid

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Limitations and Caveats

This study was terminated on 27-Nov-2017 due to low enrollment; small sample sizes make data interpretation difficult.

Results Point of Contact

• Title: Pacira Medical Information
• Organization: Pacira Pharmaceuticals, Inc.

MedInfo@pacira.com

1-855-793-9727

Study Officials

• Hassan Danesi, MD

  Pacira Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2016
• First Posted: October 4, 2016
• Study Start: October 28, 2016
• Primary Completion: November 27, 2017
• Study Completion: November 27, 2017
• Last Updated: December 11, 2020
• Results First Posted: December 11, 2020

Record last verified: 2020-12

Locations

US (5)