Factor Xa Inhibitor, PRT054021, Against Enoxaparin for the Prevention of Venous Thromboembolic Events (EXPERT)

Thromboembolism Clinical Trial

Official title:

Evaluation of the Factor Xa Inhibitor, PRT054021, Against Enoxaparin in a Randomized Trial for the Prevention of Venous Thromboembolic Events After Unilateral Total Knee Replacement (EXPERT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00375609
• Other study ID #: PRT05-003
• Status: Completed
• Phase: Phase 2
• Start date: May 2006
• Est. completion date: February 2007

Study information

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

Clinical Trial Summary

Randomized study of PRT054021 40 mg and 15 mg bid vs. enoxaparin 30 mg q12h for the prophylaxis of venous thromboembolic events after unilateral knee replacement surgery.

Description:

Approximately 200 patients undergoing unilateral knee replacement will be entered into the study and randomized to receive either enoxaparin 30 mg sq bid, PRT054021 15 mg po bid, or PRT054021 40 mg po bid for 10 to 14 days, at which time patients will undergo venography.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 215
• Est. completion date: February 2007
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• • The subject has undergone elective primary unilateral TKR (not unicompartmental). Demographic
• The subject is between the ages of 18 and 75 years.
• If the subject is a woman, she is without reproductive potential (postmenopausal for >2 years or after hysterectomy).
• The subject weighs between 50 kg (110 lbs) and 120 kg (265 lbs). Laboratory and Procedures
• The subject is willing and able to undergo unilateral venography. Medications
• The subject is willing and able to self-inject enoxaparin or receive injections q12h by a caregiver. Ethical • The subject is able to read and give written informed consent and has signed an informed consent form approved by the Investigator's IRB/IEC.

Exclusion Criteria:

• Disease Related
• Major medical and/or surgical condition which may impair oral drug absorption or metabolism.
• Immobilization for 3 or more days before surgery.
• History (including family history) or symptoms of a congenital or acquired bleeding disorder or vascular malformation; or a history of intracranial, retroperitoneal, or intraocular bleeding within the last 6 months; or is felt to be at high risk for bleeding for other reasons.
• Gastrointestinal bleeding within 90 days before surgery or endoscopically verified ulcer disease within 30 days before surgery.
• Indwelling intrathecal or epidural catheter during the prophylaxis period (except for epidural catheter if removed after surgery); or unusual difficulty in administering spinal or epidural anesthesia (eg, 3 or more attempts, "traumatic taps").
• Major surgery, ischemic stroke, or myocardial infarction within 3 months before Screening.
• Uncontrolled hypertension defined as systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) >105 mmHg.
• Hypotension defined as SBP <95 mmHg.
• Evidence at Screening of symptomatic congestive heart failure requiring treatment.
• Chronic atrial fibrillation treated with oral anticoagulants, recurrent atrial arrhythmia(s) or a history of recurrent ventricular tachycardia. Laboratory and Procedures
• Evidence at Screening of: platelet count <100,000/mm3 potassium <3.5 mEq/L hemoglobin concentration <10 g/dL or hematocrit <30% serum ALT or AST >2 times ULN serum creatinine >2.0 mg/dL (180 µm/L)
• Contraindication to venography, including to iodinated contrast medium
• QTc on Screening ECG >450 msec and/or a personal or family history of "Long QT Syndrome". Medications
• Contraindication to anticoagulation for VTE prophylaxis, including a contraindication to receiving heparin or heparinoids.
• Administration of the following drugs within 7 days before TKR: thrombolytic agents, anticoagulants and/or anti-platelet agents (eg, heparins, warfarin, dipyridamole, sulfinpyrazone, ticlopidine, dextran, clopidogrel). Aspirin up to 325 mg once daily and NSAIDs are allowed but discouraged.
• Use of class III antiarrhythmics drugs (eg, dofetilide, ibutilide, amiodarone, bretylium, sotalol) within 30 days prior to TKR. General
• Participation in any investigational drug study 30 days prior to enrollment is prohibited. Participation in a device trial prior to enrollment is acceptable.
• Any condition which could interfere with or for which the treatment of might interfere with the conduct of the study, or which would, in the opinion of the Investigator, unacceptably increase the risk of the subject's participation in the study. This would include, but is not limited to alcoholism, drug dependency or abuse, psychiatric disease, epilepsy or any unexplained blackouts.

Related Conditions & MeSH terms

• Thromboembolism

Intervention

Drug:
• Betrixaban
Capsule
• Enoxaparin
Administered subcutaneously

Locations

Country	Name	City	State
Canada	Montreal General Hospital	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Portola Pharmaceuticals

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adjudicated Venous Thromboembolism (VTE)	Incidence of adjudicated venous thromboembolism (VTE) through Day 10-14 following TKR where VTE is defined as DVT (proximal and/or distal) and/or PE. Patients were evaluated for VTE daily while hospitalized and were contacted every 2 to 4 days after discharge and before the day of the mandatory venogram to monitor for study endpoints	Through Day 10-14 following TKR surgery, at time of mandatory venogram
Primary	Incidence of Adjudicated Overt Bleeding Events: Primary Safety Endpoint	The incidence of adjudicated major and clinical relevant non-major bleeding. Major bleeding was defined as fatal, involving vital organs, requiring additional surgery or a new therapeutic procedure, or a bleeding index >=2. Bleeding Index was defined as the number of units of packed red blood cells or whole blood transfused plus the haemoglobin values before the bleeding episode minus the haemoglobin values after the bleed had stabilized (in g/dL)	Through follow-up at approximately 6 (±2) weeks after TKR surgery
Secondary	Incidence of Adjudicated Pulmonary Embolism (PE) and All Deep Vein Thrombosis (DVT) (Proximal and Distal)	Incidence of adjudicated pulmonary embolism (PE) and all deep vein thrombosis (DVT) (proximal and distal) through the time of venography on Day 10 to 14 and at follow-up at approximately 6 (±2) weeks after TKR surgery	At follow-up at approximately 6 (±2) weeks after TKR surgery