Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip…

Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended

Thromboprophylaxis After Total Hip Arthroplasty: The RECORD1 Trial

Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Muehlhofer E, Misselwitz F

Blood. 2007;110(11). Abstract #6.

Background:• Thrombosis prophylaxis is recommended for at

least 10 days, and for up to 4-5 weeks, after total hip arthroplasty (THA)

• Rivaroxaban is an oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders

Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis

After Total Hip Arthroplasty: The RECORD1 Trial

Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

Objective:• To determine the efficacy and safety of oral

rivaroxaban, compared with subcutaneous enoxaparin, for 5 weeks of thrombosis prophylaxis in patients undergoing THA




Methods:• Multinational, double-blind, double-dummy trial• Inclusion criteria:

– Patients ≥18 years, scheduled to undergo elective THR• Major exclusion criteria:

– Active bleeding or high risk of bleeding– Significant liver disease– Anticoagulant therapy that could not be stopped– Use of HIV-protease inhibitors




Study Design

Rivaroxaban 10mg qd

Start 6-8hr post-op

Enoxaparin 40mg qd

Begin evening before then restart

6-8hr post-op

Mandatory, Bilateral Venography the day after

treatment is completed

35±4 days35±4 days


Methods:• Primary efficacy endpoint (composite):

– Deep vein thrombosis (DVT)– Non-fatal pulmonary embolism (PE)– All-cause mortality

• Primary efficacy analysis:– A test for non-inferiority in the per-protocol (PP)

population followed by a test for superiority in the modified intention-to-treat (mITT) population




Methods:• The main secondary efficacy endpoint:

– Major venous thromboembolism (VTE): the composite of proximal DVT, non-fatal PE and VTE-related death

• Primary Safety Endpoint:– Major bleeding during the active treatment period

• Secondary Safety Endpoint:– Non-major bleeding during the active treatment period




Results:• A total of 4541 patients were randomized

– 4433 were eligible for the safety population– 3153 for the mITT population– 3029 for the PP population

• The criteria for non-inferiority were met and testing for superiority was performed




Results:• Rivaroxaban significantly reduced the incidence of

the primary efficacy endpoint (P<0.001) and major VTE (P<0.001), compared with enoxaparin, in the mITT population

• The incidence of major and non-major bleeding events was similar in both groups




Results

Rivaroxaban 10 mg od % (n/N)

Enoxaparin 40 mg od % (n/N)

Relative risk reduction

% (95% CI)

P-value for

differenceDVT, non-fatal PE, and all-cause mortality

1.1% (18/1595)

3.7% (58/1558)

70% (49-82%) P<0.001

Major VTE 0.2% (4/1686)

2.0% (33/1678)

88% (66-96%) P<0.001

Major bleeding 0.3% (6/2209)

0.1% (2/2224) -- P=0.178

Non-major bleeding 5.8% (128/2209)

5.8% (129/2224) -- P=1.000


6

Inci

denc

e (%

)

0

1

2

3

4

5

Rivaroxaban10 mg once daily

18/1595

Enoxaparin40 mg once daily

58/1558

3.7%

1.1%

RRR* = 70%ARD† = –2.6% (–3.7, –1.5)

p<0.001

*Relative risk reduction based on raw incidences; †absolute weighted risk difference (with 95% CI); mITT population, n=3153

Total VTE

Primary Efficacy Endpoints


Inci

denc

e (%

)

0

1

2

3

4


6/2193


11/2206

ARD† = –0.2% (–0.6, 0.1)p=0.222

0.3%0.5%In

cide

nce

(%)

0

1

2

3

4


4/1686


33/1678

RRR* = 88%ARD† = –1.7% (–2.5,–1.0 )

p<0.001

2.0%0.2%

Major VTE Symptomatic VTE

in safety population

mITT population valid for major VTE, n=3364; safety population who underwent surgery, n=4399; *relative risk reduction based on raw incidences; †absolute weighted risk difference (with 95% CI)

Primary Efficacy Endpoints Cont.


On-treatment major bleeding; *unweighted absolute risk difference (with 95% CI); safety population, n=4433

Major bleeding4

0

1

2

3

p=0.178ARD* = 0.18% (–0.1,

0.5)

0.09% 0.27%


6/2209


2/2224

Inci

denc

e (%

)

Safety Endpoints


Conclusions:• Rivaroxaban was significantly more effective than

enoxaparin for extended prophylaxis after THA, with a similar safety profile

• This is the first pivotal trial to demonstrate the efficacy and safety of a fixed, unmonitored dose of an oral, direct Factor Xa inhibitor – rivaroxaban – for extended thromboprophylaxis after THA




Documents

Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip…