Switching Drug Therapy for the Prevention of Blood Clot Formation From Enoxaparin to Rivaroxaban After Orthopedic Surgery for Either Total Hip or Total Knee Replacement

Osteoarthritis, Knee Clinical Trial

Official title:

A Open-Label Study of the Transition to Rivaroxaban From Low-Molecular Weight Heparin for Venous Thromboembolism Prophylaxis After Total Joint Replacement: The Safe Simple Transitions Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01094886
• Other study ID #: CR016531
• Secondary ID: RIVAROXCPK3001
• Status: Completed
• Phase: Phase 3
• First received: March 25, 2010
• Last updated: May 3, 2013
• Start date: March 2010
• Est. completion date: December 2010

Study information

• Verified date: May 2013
• Source: Ortho-McNeil Janssen Scientific Affairs, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The study will describe the short-term effects the study drug, rivaroxaban, has on the body when a patient is switched from enoxaparin injection (by needle) to oral rivaroxaban (by mouth) for the prevention of blood clotting in the veins after elective total hip or total knee replacement surgery. After providing written informed consent, screening procedures will be completed to assess eligibility. After enrollment, all patients will be switched from enoxaparin to rivaroxaban. Blood samples for the short-term effects of rivaroxaban will be taken at various times while in the subacute unit. At the time of discharge, if the study doctor feels it is appropriate, an adequate supply of rivaroxaban will be provided to complete the full course of therapy. Upon completion of rivaroxaban therapy, all patients will be required to have final study procedures performed. Safety evaluations at the final visit will include clinical blood laboratory tests, a physical examination, urine pregnancy test (if applicable), recording of any adverse events including details regarding any bleeding episodes or blood clot events, and assessment of the surgical wound. All patients will return any unused study medication and study participation will be complete.

Description:

The study medication, rivaroxaban, is an oral (by mouth) medication. Rivaroxaban directly inhibits one of the clotting mechanisms in the blood that is involved in the formation of blood clots in the veins in the body. The ability to inhibit blood clotting will be measured. Rivaroxaban is currently approved in the European Union by the European Medicines Agency (EMEA) for the prevention of blood clots in veins in orthopedic (bone) surgical patients who have had elective total joint (hip or knee) replacement. It is currently under review by the Food and Drug Administration (FDA) in the United States for this same indication. Enoxaparin is a medication that is injected into the fat tissue under the skin and is approved by the FDA for the treatment and prevention of blood clot formation in the veins. The goal of the study is to describe the short-term effects that the study drug has on the body when a patient is switched from enoxaparin to rivaroxaban. The study hypothesis, or theory, is that when switched from enoxaparin to rivaroxaban the ability of the body to inhibit blood clotting activity will continue. This is an open-label study which means that all persons involved in the study will know what study drug is being given to them. It is a single-arm study which means that all patients will be administered the same study medication, rivaroxaban. The study will be conducted at large orthopedic centers in the United States. All patients will have had elective total hip or total knee replacement surgery. While in the hospital, eligible patients will have been receiving enoxaparin either 30 mg twice a day or 40 mg once daily. Upon discharge from the hospital all eligible patients will require a stay in a subacute unit and continuing medication for blood clot prevention. After providing written informed consent, patients will have screening procedures completed to determine eligibility. Safety evaluations at the screening procedure will include a physical examination, vital signs, and clinical blood laboratory tests. Women, who are able to bear children, will also have a screening blood pregnancy test performed. A negative pregnancy test is needed to be in the study. Just before receiving the first dose of rivaroxaban, 10 mg, blood sampling for the short-term effects of rivaroxaban will begin and continue at various times. All patients will receive 10 mg of rivaroxaban daily. In addition, the study doctor will do an assessment of the surgical wound. At the time of discharge from the subacute unit, if the study doctor feels it is appropriate, an adequate supply of rivaroxaban will be provided to complete the full course of therapy. If a patient withdraws his/her consent prior to completion of the study, the appropriate course of blood clot prevention therapy will be prescribed by the study doctor. Upon completion of rivaroxaban therapy, all patients will be required to have final study procedures performed. Those patients who continue oral rivaroxaban after discharge from the subacute unit will be required to return for an office visit for final study procedures either at the time of completion of rivaroxaban therapy or at the surgical follow-up visit. Patients who have rivaroxaban discontinued prior to discharge from the subacute unit will have final study procedures completed at that time and a subsequent office visit will not be required. In all cases, the prescribed rivaroxaban therapy must have been completed prior to the time of the final visit. Safety evaluations at the final visit will include clinical laboratory blood tests, a physical examination, urine pregnancy test (if applicable), recording of any adverse events including details regarding any bleeding episodes or blood clot events, and assessment of the surgical wound. All patients will return any unused study medication and study participation will be complete. All patients will receive oral rivaroxaban 10mg daily. First dose of rivaroxaban will be given within 2 days after admission to the subacute unit, in the morning within 12 hrs (if 30mg twice a day) or 24 hours (if 40mg daily) of the enoxaparin dose. Patients will then continue to receive a daily 10 mg dose each morning. The total duration of combined therapy (enoxparin plus rivaroxaban) may not exceed 35 days for patients with total hip replacement or 14 days with total knee replacement.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Undergone elective total hip or knee replacement surgery

• Received postoperative venous blood clot prevention therapy within 24 hours of the surgery

• Currently prescribed enoxaparin 30mg subcutaneous (SQ) twice a day or 40mg SQ daily for venous blood clotting prevention with an expected duration of continued prevention therapy of at least 3 days after admission to a subacute unit

• Discharged from the hospital to a subacute unit (including skilled nursing facilities and rehabilitation units) and committed to remaining in the unit for the duration of the Pharmacodynamic blood sampling period of the study

Exclusion Criteria:

• Platelet count <90,000/µL based on screening laboratory assessments

• active internal bleeding or high risk of bleeding

• history of, or condition associated with, increased bleeding risk including

• planned invasive procedure with potential for uncontrolled bleeding, including major surgery

• sustained uncontrolled high blood pressure, defined as systolic blood pressure =180 mmHg or diastolic blood pressure =100 mmHg

• clinically significant kidney disease and/or impaired kidney function

• clinically significant liver disease

• anemia

• known allergies, hypersensitivity, or intolerance to rivaroxaban

• indication for anticoagulant (blood thinning) therapy for a condition other than blood clot prevention

• anticipated need for treatment with a prescription or nonprescription non-steroidal anti-inflammatory drugs (NSAIDs)

• any patient who has taken more than one or two doses of aspirin (>100 mg/dose) in the week prior to enrollment will not be allowed to participate

• Drug addiction or alcohol abuse within 3 years prior to screening

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Arthritis
• Osteoarthritis
• Osteoarthritis, Hip
• Osteoarthritis, Knee
• Thromboembolism

Intervention

Drug:
• Rivaroxaban
10mg tablet daily, receiving the first dose within two days after admission to the subacute unit. The total duration of combined venous blood clot prevention therapy with enoxaparin and rivaroxaban may not exceed 35 days for patients with total hip replacement or 14 days with total knee replacement

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ortho-McNeil Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Summary of Change From Day 3 to Day 1 in Maximum Anti-Factor Xa (aFXa)	Descriptive statistics for per-patient maximum Anti-Factor Xa laboratory value selected from the 7 consecutive blood draws (0, 2, 4, 6, 8, 12 and 24 hrs post dose) on Day 1 and Day 3	Day 1, Day 3	No
Primary	Summary of Change From Day 3 to Day 1 in Maximum Prothrombin Time	Descriptive statistics for per-patient maximum prothrombin time laboratory value selected from the 7 consecutive blood draws (0, 2, 4, 6, 8, 12 and 24 hrs post dose) on Day 1 and Day 3	Day 1, Day 3	No
Secondary	Summary of Change From Day 1 to Day 3 in Area Under the Curve (AUC) of aFXa	Descriptive statistics for Area Under the Curve (AUC) on Study Day 1 and Day 3 for Anti-Factor Xa, based on the 7 consecutive blood draws at 0, 2, 4, 6, 8, 12 and 24 hours post dose	Day 1, Day 3	No
Secondary	Summary of Change From Day 1 to Day 3 in AUC of Prothrombin Time	Descriptive statistics for AUC on Study Day 1 and Day 3 for prothrombin time, based on the 7 consecutive blood draws at 0, 2, 4, 6, 8, 12 and 24 hours post dose	Day 1, Day 3	No