Dabigatran Etexilate vs Enoxaparin in Prevention of Venous Thromboembolism (VTE) Post Total Knee Replacement

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Thromboembolism; Arthroplasty, Replacement, Knee

Treatments: Drug: Enoxaparin; Drug: Dabigatran Dose 2 - day 1; Drug: Dabigatran Dose 2 - day 2 to completion; Drug: Dabigatran Dose 1 - day 1; Drug: Dabigatran Dose 1 - day 2 to completion

Study type: Interventional

Funder types: Industry

Identifiers

NCT00152971

1160.24

Details and patient eligibility

About

To determine the comparative efficacy and safety of two different doses (75mg day 1 followed by 150 mg day 2-completion, and 110 mg day 1 followed by 220 mg day 2-completion) of dabigatran administered orally (capsules), compared to enoxaparin 30 mg twice a day subcutaneous, in prevention of venous thromboembolism in patients with primary elective total knee replacement surgery

Enrollment: 2,615 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria INCLUSION CRITERIA

1. Patients scheduled to undergo a primary, unilateral elective total knee repla cement.
2. Male or female 18 years of age or older.
3. Patients weighing at least 40 kg.
4. Written informed consent prior to the start of study participation.

Exclusion criteria EXCLUSION CRITERIA

1. History of bleeding diathesis.

2. Constitutional or acquired coagulation disorders that in the investigator's judgment puts the patient at excessive risk for bleeding.

3. Major surgery or trauma (e.g. hip fracture) within the last 3 months.

4. Recent unstable cardiovascular disease, such as uncontrolled hypertension at the time of enrollment (investigator's judgment) or history of myocardial infarction within the last 3 months.

5. Spinal or epidural anesthesia, for which more than 3 attempts (sticks) at placement were made, or the placement was traumatic.

   Please note that patients, who are not excluded under this criterion, are to have the catheter pulled at the completion of surgery.

6. Any history of hemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, arteriovenous (AV) malformation or aneurysm.

7. History of VTE or pre-existing condition requiring anticoagulant therapy.

8. Clinically relevant bleeding (e.g. gastrointestinal, pulmonary, intraocular or urogenital bleeding) within the last 6 months.

9. Gastric or duodenal ulcer within the last 6 months.

10. Liver disease expected to have any potential impact on survival (e.g. hepatitis B or C, cirrhosis, but not Gilbert's syndrome or hepatitis A with complete recovery).

11. Elevated AST or ALT >2x upper limit of normal, based on central lab results or local lab results within 1 month before enrollment.

12. Known severe renal insufficiency (CrCl < 30 mL/min). In order to determine patient inclusion/exclusion, creatinine clearance (CrCl) needs to be calculated only if serum creatinine is elevated or renal insufficiency is suspected.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2,615 participants in 3 patient groups

Dabigatran Dose 1

Experimental group

Description:

low dose regimen taken once daily

Treatment:

Drug: Dabigatran Dose 1 - day 1

Drug: Dabigatran Dose 1 - day 2 to completion

Dabigatran Dose 2

Experimental group

Description:

high dose regimen taken once daily

Treatment:

Drug: Dabigatran Dose 2 - day 1

Drug: Dabigatran Dose 2 - day 2 to completion

Enoxaparin

Active Comparator group

Description:

30 mg subcutaneously twice daily

Treatment:

Drug: Enoxaparin