XANTUS: rationale and design of a noninterventional study of rivaroxaban for the prevention of stroke in patients with atrial fibrillation

Figures & data

Table 1 Clinical studies comprising the XANTUS program

Studya	XANTUSb	XANTUS-EL	XANAPc	XANTUS-CN
NCT identifier	NCT01606995	NCT01800006	NCT01750788	Not yet available
Estimated enrollment	6,000	At least 10,000 patients expected across all three studies
First patient, first visit (date)	June 12, 2012	July 18, 2013	February 6, 2013	In planning
Primary geographic region	European union, plus enrollment in Canada	Eastern Europe, Eastern Mediterranean, Middle East, Latin America	Asia-Pacific	People’s Republic of china

Notes:

a All studies will use the same design, database, and adjudication procedures;

b the parent study and subject of this paper;

c the East Asia subanalysis of ROCKET AF demonstrated that the 20 mg once-daily dose did not need to be adjusted in patients in this region, and that results from the East Asian population were consistent with those from the overall study.¹⁷

Abbreviations: XANTUS, Xarelto^® for Prevention of Stroke in Patients with Atrial Fibrillation; XANTUS-EL, Xarelto^® for Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation, Eastern Europe, Middle East, Africa and Latin America; XANAP, Xarelto^® for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific; XANTUS-CN, Xarelto^® for Prevention of Stroke in Patients with Atrial Fibrillation – China.

Figure 1 XANTUS study design, an observational, single-arm cohort study. The objective is to collect real-life data on adverse events, bleeding, thromboembolic events, and mortality in patients with nonvalvular AF treated with rivaroxaban. The same basic design will be used for all studies in the XANTUS program.

Notes: ^aProtocol does not define exact referral dates for follow-up visits (every 3 months recommended); ^bin patients discontinuing rivaroxaban before 1 year, the end of the observation period is 30 days after the last dose. XANTUS (ClinicalTrials.gov: NCT01606995).
Abbreviations: AF, atrial fibrillation; CNS, central nervous system; XANTUS, Xarelto^® for Prevention of Stroke in Patients with Atrial Fibrillation.

Table S1 Primary efficacy results for ROCKET AF

Study population and analysis period	Median follow-up (days)	Rivaroxaban		Warfarin		Hazard ratio (95% CI)b	P-value
		na	Event rate (%/year)	na	Event rate (%/year)		Noninferiority	Superiority
Per protocol on treatment	590	6,958	1.7	7,004	2.2	0.79 (0.66–0.96)	<0.001	–
Safety on treatmentc	590	7,061	1.7	7,082	2.2	0.79 (0.65–0.95)	–	0.02
Intention-to-treatd	707	7,081	2.1	7,090	2.4	0.88 (0.75–1.03)	<0.001	0.12

Notes: From Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–891.¹ Copyright © 2011 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

a Number of patients;

b hazard ratio is for rivaroxaban versus warfarin;

c safety population included all patients who received at least one dose of study medication; on-treatment analyses evaluated all events occurring while patients were receiving study medication or within 2 days of permanent discontinuation;

d intention-to-treat follow-up was until notification of study termination. ROCKET AF (ClinicalTrials.gov: NCT00403767).

Abbreviations: CI, confidence interval; ROCKET AF, Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation.

Table S2 Rates of bleeding outcomes in ROCKET AF

Outcome	Rivaroxaban		Warfarin		Hazard ratio (95% CI)a	P-value
	Events n (%)	Event rate (%/year)	Events n (%)	Event rate (%/year)
Principal safety outcome (major + nonmajor clinically relevant bleeding)	1,475 (20.7)	14.9	1,449 (20.3)	14.5	1.03 (0.96–1.11)	0.44
Major bleeding
Any	395 (5.6)	3.6	386 (5.4)	3.4	1.04 (0.90–1.20)	0.58
Decrease in Hb ≥2 g/dL	305 (4.3)	2.8	254 (3.6)	2.3	1.22 (1.03–1.44)	0.02
Transfusion	183 (2.6)	1.6	149 (2.1)	1.3	1.25 (1.01–1.55)	0.04
Critical bleedingb	91 (1.3)	0.8	133 (1.9)	1.2	0.69 (0.53–0.91)	0.007
Fatal bleeding	27 (0.4)	0.2	55 (0.8)	0.5	0.50 (0.31–0.79)	0.003
Intracranial hemorrhage	55 (0.8)	0.5	84 (1.2)	0.7	0.67 (0.47–0.93)	0.02

Notes: From Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–891.¹ Copyright © 2011 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

a Hazard ratio is for rivaroxaban versus warfarin;

b critical organ bleeding refers to bleeding in intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular (with compartment syndrome), or retroperitoneal locations. ROCKET AF (ClinicalTrials.gov: NCT00403767).

Abbreviations: CI, confidence interval; Hb, hemoglobin; ROCKET AF, Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation.

WongKSHuDYOommanARivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trialStroke Epub4242014

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PatelMRMahaffeyKWGargJRivaroxaban versus warfarin in nonvalvular atrial fibrillationN Engl J Med20113651088389121830957

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