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

Total Knee Arthroplasty Clinical Trial

Official title:

A Randomized, Single-Blind, Active-Controlled, Dose-Ranging Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Local Administration of DepoTXA for Reduced Postsurgical Bleeding in Subjects Undergoing Total Knee Arthroplasty

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02922582
• Other study ID #: 404-C-201
• Status: Terminated
• Phase: Phase 2
• Start date: October 28, 2016
• Est. completion date: November 27, 2017

Study information

• Verified date: December 2020
• Source: Pacira Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

Approximately 60 subjects (15 per arm) are planned for enrollment. Subjects will be randomized in a 1:1:1:1 ratio to receive either DepoTXA 400 mg, DepoTXA 800 mg, DepoTXA 1200 mg, or IV TXA (Cyklokapron® 1 gram).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: November 27, 2017
• Est. primary completion date: November 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female, =18 years of age at screening.

2. Scheduled to undergo elective unilateral open TKA under general, spinal, or regional anesthesia.

3. American Society of Anesthesiology (ASA) physical status 1, 2, or 3.

4. 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.

5. Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.

Exclusion Criteria:

1. Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.

2. Planned concurrent surgical procedure (e.g., bilateral TKA).

3. Prior open knee surgery on ipsilateral knee. Prior arthroscopy is permitted.

4. 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).

5. Contraindication or hypersensitivity to TXA.

6. History of thrombosis or prior Venous thromboembolism (VTE).

7. Known coagulopathy or active intravascular clotting.

8. Prior myocardial infarction.

9. Prior cardiovascular accident (stroke) or subarachnoid hemorrhage.

10. History of epilepsy.

11. Presence of an intravascular stent.

12. History of impaired kidney function, chronic respiratory disease, rheumatoid arthritis, coagulopathy, or loss of sensation in extremities.

13. Renal insufficiency (serum creatinine level >2 mg/dL).

14. Anemia (Hb level <10 g/dL).

15. Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments.

16. Acquired defective color vision.

17. Malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.

18. Suspected or known history of drug or alcohol abuse within the previous year.

19. Body weight <50 kg (110 pounds) or a body mass index >44 kg/m2.

20. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.

Related Conditions & MeSH terms

• Hemorrhage
• Total Knee Arthroplasty

Intervention

Drug:
• DepoTXA

• Tranexamic Acid

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ohio State University/Wexner Medical Center	Columbus	Ohio
United States	Ortho Arizona	Gilbert	Arizona
United States	Kendall Regional Medical Center	Miami	Florida
United States	University of Miami Hospital	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pacira Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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	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	Neurological assessment at 12, 24, 36, 48, 60, 72, and 96 hours after study drug administration	12, 24, 36, 48, 60, 72, and 96 hours after study drug administration
Secondary	Incidence of Reoperation Due to Hematoma or Wound Dehiscence	Number of subjects who underwent reoperation due to hematoma or wound dehiscence	Through day 60
Secondary	Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused)		Day 60
Secondary	Number of Participants With 90° Passive and Active Knee Flexion		24, 48, and 72 hours
Secondary	Time to Complete Timed Up-and-Go (TUG) Test	Physical therapy assessment (Timed Up-and-Go (TUG) test) was conducted once postsurgically on Day 1; at approximately 8:00 am and 8:00 pm (±2 hours) daily from Day 2 through hospital discharge; and on Day 7	Day 1; at approximately 8:00 am and 8:00 pm (±2 hours) daily from Day 2 through hospital discharge; and on Day 7
Secondary	Change in Knee and Thigh Measurements	Leg difference in change from baseline is calculated by = (Operated Leg Change from Baseline) - (Non-Operated Leg Change from Baseline)	48 hours and Day 7
Secondary	Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours	Numerical rating scale (NRS) at rest pain score (0 [no pain] to 10 [worst possible pain]) upon arrival at the PACU; at each in-hospital vital sign assessment beginning with the 2-hour assessment and ending with the 48-hour assessment; and the Day-7 follow-up visit. Summary is provided as area under the curve (AUC) of NRS from timepoint 0 to 24 hours, 0 to 48 hours, and 24 to 48 hours.	Preoperative; arrival in Post-Anesthesia Care Unit (PACU); 2, 4, 6, 8, 12, 16, 24, 36, 48 hours, Day 7