Table 3, Details of Included Studies - Rivaroxaban (Xarelto)

		EINSTEIN DVT	EINSTEIN PE
Designs & Populations	Study design	Multi-centre, randomized, open-label, parallel-group, active controlled, event-driven non-inferiority study; central independent adjudication committee for suspected clinical outcomes was blinded to treatment allocation
Locations	Approximately 300 centres worldwide in more than 30 countries including US, Canada, Australia, and countries from western and eastern Europe, Asia, and Africa
Randomized (N)	3,449 patients	4,832 patients
Inclusion criteria	Confirmed proximal DVT without symptomatic PE	Confirmed acute symptomatic PE with or without symptomatic DVT
Exclusion criteria	Thrombectomy, insertion of a caval filter, or use of a fibrinolytic drug to treat the current thrombotic episode Treatment with therapeutic dosages of heparin, LMWH, or fondaparinux for more than 48 hours pre-randomization, or more than a single dose of VKA pre-randomization Creatinine clearance < 30 mL/min Active bleeding or high risk of bleeding, contraindicating treatment with enoxaparin or VKA, as well as any other contraindication listed in the local labelling of warfarin, acenocoumarol, or enoxaparin
Drugs	Intervention	Rivaroxaban 15 mg b.i.d. for 3 weeks, followed by 20 mg q.d. P.O.
Comparator(s)	Enoxaparin 1 mg/kg b.i.d. SC VKA (acenocoumarol or warfarin) INR 2.0–3.0 P.O.
Duration	Phase:
Active treatment	3, 6, or 12 months
Follow-up	30 days
Outcomes	Primary end point	Recurrent VTE, i.e., the composite of recurrent DVT or non-fatal or fatal PE
Other end points	Composite of the primary efficacy outcome and all deaths Health care resources utilization Net clinical benefit as composite of the primary efficacy outcome and major bleeding events Individual components of the primary and secondary efficacy outcome
Notes	Publications	The EINSTEIN Investigators 2010,⁵ Buller et al. 2008,²⁸ and the Clinical Study Report⁴	Buller et al. 2012,⁶ Van Es et al. 2013²⁹ and the Clinical Study Report⁷

EINSTEIN DVT

EINSTEIN PE

Designs & Populations

Study design

Multi-centre, randomized, open-label, parallel-group, active controlled, event-driven non-inferiority study; central independent adjudication committee for suspected clinical outcomes was blinded to treatment allocation

Locations

Approximately 300 centres worldwide in more than 30 countries including US, Canada, Australia, and countries from western and eastern Europe, Asia, and Africa

Randomized (N)

3,449 patients

4,832 patients

Inclusion criteria

Confirmed proximal DVT without symptomatic PE

Confirmed acute symptomatic PE with or without symptomatic DVT

Exclusion criteria

Thrombectomy, insertion of a caval filter, or use of a fibrinolytic drug to treat the current thrombotic episode
Treatment with therapeutic dosages of heparin, LMWH, or fondaparinux for more than 48 hours pre-randomization, or more than a single dose of VKA pre-randomization
Creatinine clearance < 30 mL/min
Active bleeding or high risk of bleeding, contraindicating treatment with enoxaparin or VKA, as well as any other contraindication listed in the local labelling of warfarin, acenocoumarol, or enoxaparin

Drugs

Intervention

Rivaroxaban 15 mg b.i.d. for 3 weeks, followed by 20 mg q.d. P.O.

Comparator(s)

Enoxaparin 1 mg/kg b.i.d. SC VKA (acenocoumarol or warfarin) INR 2.0–3.0 P.O.

Duration

Phase:

Active treatment

3, 6, or 12 months

Follow-up

30 days

Outcomes

Primary end point

Recurrent VTE, i.e., the composite of recurrent DVT or non-fatal or fatal PE

Other end points

Composite of the primary efficacy outcome and all deaths
Health care resources utilization
Net clinical benefit as composite of the primary efficacy outcome and major bleeding events
Individual components of the primary and secondary efficacy outcome

Notes

Publications

The EINSTEIN Investigators 2010,⁵ Buller et al. 2008,²⁸ and the Clinical Study Report⁴

Buller et al. 2012,⁶ Van Es et al. 2013²⁹ and the Clinical Study Report⁷

From: 3, RESULTS

Rivaroxaban (Xarelto): Treatment of Venous Thromboembolic Events (Deep Vein Thrombosis [DVT], Pulmonary Embolism [PE]) and Prevention of Recurrent DVT and PE [Internet].

Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2015 Aug.

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Table 3Details of Included Studies