MARINER: A Study of Rivaroxaban (JNJ-39039039) on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02111564
• Collaborator: Bayer (Industry)
• Enrollment: 12,024
• Locations: 617
• Arms: 2
• Actual Duration (Months): 51.8
• Patients Per Site: 19.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of rivaroxaban compared with placebo in the prevention of symptomatic venous thromboembolism (VTE) events and VTE-related death post-hospital discharge in high-risk, medically ill patients.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Respiratory Insufficiency; Stroke Acute; Infectious Diseases; Rheumatic Diseases	Drug: Rivaroxaban, 10 mg; Drug: Rivaroxaban, 7.5 mg; Drug: Placebo	Phase 3

Detailed Description

This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect)-controlled, event-driven, multicenter study in patients who are hospitalized for a specific acute medical illness and have other risk factors for venous thromboembolism (VTE). The study is designed to evaluate rivaroxaban in the prevention of symptomatic VTE events and VTE-related deaths for a period of 45 days post-hospital discharge. The study will consist of a screening phase, a 45-day double-blind treatment phase, and a 30-day follow-up phase. Study drug will start at randomization (Day 1), and will continue until Day 45 (inclusive). A total of approximately 12000 patients will be randomly assigned to either rivaroxaban or placebo in a 1:1 ratio. The total duration for a patient who completes the study after randomization is expected to be 75 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12024 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Prevention
• Official Title: Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk
• Actual Study Start Date: Jan 7, 2014
• Actual Primary Completion Date: Mar 6, 2018
• Actual Study Completion Date: May 3, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rivaroxaban Each patient will receive either 10 mg or 7.5 mg rivaroxaban tablet once daily orally (by mouth) for 45 days. The dosing will depend on a creatinine clearance at screening.	Drug: Rivaroxaban, 10 mg; Patients, randomly allocated to the rivaroxaban arm, with a creatinine clearance at screening greater than or equal to (>=)50 mL/min will receive 10 mg rivaroxaban tablet with or without food.; Other Names: Xarelto BAY59-7939 ; Drug: Rivaroxaban, 7.5 mg; Patients, randomly allocated to the rivaroxaban arm, with a creatinine clearance at screening from >=30 to less than (<)50 mL/min will receive 7.5 mg rivaroxaban tablet with or without food.; Other Names: Xarelto BAY59-7939
Placebo Comparator: Placebo Each patient will receive matching placebo tablet once daily orally (by mouth) for 45 days.	Drug: Placebo; All patients, randomly allocated to the placebo arm, will receive one placebo tablet with or without food.

Outcome Measures

Primary Outcome Measures

1. Time From Randomization to First Occurrence of Composite of All Symptomatic Venous Thromboembolism (VTE) and VTE Related Death Adjudicated by Clinical Event Committee (CEC) [Up to Day 45]

   Symptomatic VTE included lower extremity deep vein thrombosis (DVT) and non-fatal pulmonary embolism (PE). Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.

2. Event Rate Based on Time From Randomization to the First Occurrence of Major Bleeding Adjudicated by CEC [From randomization to 2 days after the last dose (Day 45)]

   A major bleeding event was defined using validated International Society on Thrombosis and Haemostasis (ISTH) bleeding criteria. A major bleeding event was defined as overt bleeding that was associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or a critical site defined as intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or a fatal outcome. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or last dose + 2 days.

Secondary Outcome Measures

1. Event Rate Based on Time From Randomization to First Occurrence of VTE-Related Death Adjudicated by CEC [Up to Day 45]

   Event rate based on time from randomization to first occurrence of VTE-related death (adjudicated by CEC) was assessed. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.

2. Event Rate Based on Time From Randomization to the First Occurrence of a Symptomatic Venous Thromboembolism Event (VTE) Adjudicated by CEC [Up to Day 45]

   Event rate based on time from randomization to the first occurrence of a symptomatic VTE (adjudicated by CEC) was assessed. Symptomatic VTE included lower extremity DVT and non-fatal PE. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.

3. Event Rate Based on Time From Randomization to the First Occurrence of a Composite of Symptomatic VTE and All-Cause Mortality (ACM) Adjudicated by CEC [Up to Day 45]

   Event rate based on time from randomization to the first occurrence of a composite of symptomatic VTE and ACM (adjudicated by CEC) was assessed. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.

4. Event Rate Based on Time From Randomization to the First Occurrence of a Composite of Symptomatic VTE, Myocardial Infarction (MI), Non-Hemorrhagic Stroke, and Cardiovascular (CV) Death Adjudicated by CEC [Up to Day 45]

   Event rate based on time from randomization to the first occurrence of a composite of symptomatic VTE (lower extremity DVT and non-fatal PE), MI, non-hemorrhagic stroke, and CV death (death due to a known CV cause and death in which a CV cause cannot be ruled out; by this definition, a VTE-related death was considered a CV death) as adjudicated by CEC was reported. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.

5. Event Rate Based on Time From Randomization to First Occurrence of All-Cause Mortality (ACM) Adjudicated by CEC [Up to Day 45]

   Event rate based on time from randomization to first occurrence of ACM (adjudicated by CEC) was assessed. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• The duration of the index hospitalization must have been at least 3 and no more than 10 consecutive days

• Must meet venous thromboembolism (VTE) risk criteria with a total modified Improve VTE Risk Score of: greater than or equal 4, or 3 with D-dimer > 2* upper limit of normal (ULN), or 2 with D-dimer > 2*ULN

Key Exclusion Criteria:

• Any serious bleeding within 3 months prior to randomization or occurring during index hospitalization

• Serious trauma (including head trauma) within 4 weeks before randomization

• History of hemorrhagic stroke at any time in the past

• Any medical condition that requires chronic use of any parenteral or oral anticoagulation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Mobile	Alabama	United States
3		Sheffield	Alabama	United States
4		Scottsdale	Arizona	United States
5		Fort Smith	Arkansas	United States
6		Little Rock	Arkansas	United States
7		Anaheim	California	United States
8		Beverly Hills	California	United States
9		Fullerton	California	United States
10		Los Angeles	California	United States
11		Newport Beach	California	United States
12		Orange	California	United States
13		Sacramento	California	United States
14		San Jose	California	United States
15		San Marino	California	United States
16		Santa Ana	California	United States
17		Colorado Springs	Colorado	United States
18		Bridgeport	Connecticut	United States
19		Danbury	Connecticut	United States
20		New Haven	Connecticut	United States
21		Waterbury	Connecticut	United States
22		Washington	District of Columbia	United States
23		Atlantis	Florida	United States
24		Bay Pines	Florida	United States
25		Bradenton	Florida	United States
26		Brandon	Florida	United States
27		Celebration	Florida	United States
28		Clearwater	Florida	United States
29		Daytona Beach	Florida	United States
30		Jacksonville Beach	Florida	United States
31		Jacksonville	Florida	United States
32		Largo	Florida	United States
33		Miami	Florida	United States
34		Orlando	Florida	United States
35		Pensacola	Florida	United States
36		Saint Cloud	Florida	United States
37		Sebring	Florida	United States
38		Tampa	Florida	United States
39		Vero Beach	Florida	United States
40		Wellington	Florida	United States
41		West Palm Beach	Florida	United States
42		Atlanta	Georgia	United States
43		Marietta	Georgia	United States
44		Idaho Falls	Idaho	United States
45		Chicago	Illinois	United States
46		Normal	Illinois	United States
47		North Chicago	Illinois	United States
48		Hammond	Indiana	United States
49		Lafayette	Indiana	United States
50		Michigan City	Indiana	United States
51		Des Moines	Iowa	United States
52		Kansas City	Kansas	United States
53		Topeka	Kansas	United States
54		Alexandria	Louisiana	United States
55		Lafayette	Louisiana	United States
56		Metairie	Louisiana	United States
57		Minden	Louisiana	United States
58		New Orleans	Louisiana	United States
59		Shreveport	Louisiana	United States
60		Slidell	Louisiana	United States
61		Rockport	Maine	United States
62		Annapolis	Maryland	United States
63		Baltimore	Maryland	United States
64		Boston	Massachusetts	United States
65		Detroit	Michigan	United States
66		Royal Oak	Michigan	United States
67		Saginaw	Michigan	United States
68		Troy	Michigan	United States
69		Minneapolis	Minnesota	United States
70		Saint Paul	Minnesota	United States
71		Bridgeton	Missouri	United States
72		Columbia	Missouri	United States
73		Saint Louis	Missouri	United States
74		Omaha	Nebraska	United States
75		Las Vegas	Nevada	United States
76		Atlantic City	New Jersey	United States
77		Bridgewater	New Jersey	United States
78		Marlton	New Jersey	United States
79		Newark	New Jersey	United States
80		Albuquerque	New Mexico	United States
81		Albany	New York	United States
82		Buffalo	New York	United States
83		Cortlandt Manor	New York	United States
84		Jamaica	New York	United States
85		Johnson City	New York	United States
86		Manhasset	New York	United States
87		New Hyde Park	New York	United States
88		New York	New York	United States
89		Staten Island	New York	United States
90		Valhalla	New York	United States
91		Durham	North Carolina	United States
92		Greensboro	North Carolina	United States
93		Raleigh	North Carolina	United States
94		Statesville	North Carolina	United States
95		Canton	Ohio	United States
96		Cincinnati	Ohio	United States
97		Cleveland	Ohio	United States
98		Columbus	Ohio	United States
99		Maumee	Ohio	United States
100		Springfield	Ohio	United States
101		Willoughby	Ohio	United States
102		Oklahoma City	Oklahoma	United States
103		Portland	Oregon	United States
104		Abington	Pennsylvania	United States
105		Camp Hill	Pennsylvania	United States
106		Chambersburg	Pennsylvania	United States
107		Doylestown	Pennsylvania	United States
108		Jefferson Hills	Pennsylvania	United States
109		Johnstown	Pennsylvania	United States
110		Lancaster	Pennsylvania	United States
111		Langhorne	Pennsylvania	United States
112		Philadelphia	Pennsylvania	United States
113		Pittsburgh	Pennsylvania	United States
114		Shippensburg	Pennsylvania	United States
115		Pawtucket	Rhode Island	United States
116		Columbia	South Carolina	United States
117		Summerville	South Carolina	United States
118		Athens	Tennessee	United States
119		Amarillo	Texas	United States
120		Austin	Texas	United States
121		Channelview	Texas	United States
122		Corsicana	Texas	United States
123		Dallas	Texas	United States
124		Fort Worth	Texas	United States
125		Houston	Texas	United States
126		McAllen	Texas	United States
127		Tyler	Texas	United States
128		Norfolk	Virginia	United States
129		Richmond	Virginia	United States
130		Roanoke	Virginia	United States
131		Richland	Washington	United States
132		Seattle	Washington	United States
133		Huntington	West Virginia	United States
134		La Crosse	Wisconsin	United States
135		Marshfield	Wisconsin	United States
136		Bahia Blanca		Argentina
137		Buenos Aires		Argentina
138		Ciudad de Buenos Aires		Argentina
139		Cordoba		Argentina
140		Coronel Suarez		Argentina
141		Corrientes		Argentina
142		Córdoba		Argentina
143		Esperanza		Argentina
144		La Plata		Argentina
145		Merlo		Argentina
146		Moron		Argentina
147		Munro		Argentina
148		Rosario		Argentina
149		Santa Fe		Argentina
150		Santa Fé		Argentina
151		Tucuman		Argentina
152		Bedford Park		Australia
153		Box Hill		Australia
154		Caboolture		Australia
155		Cairns		Australia
156		Chermside		Australia
157		East Saint Kilda		Australia
158		Kogarah		Australia
159		Launceston		Australia
160		Lismore		Australia
161		Meadowbrook		Australia
162		Milton		Australia
163		Nedlands		Australia
164		Parkwood		Australia
165		Penrith		Australia
166		Redcliffe		Australia
167		South Brisbane		Australia
168		Sydney		Australia
169		VIC, Parkville		Australia
170		Feldkirch		Austria
171		Graz		Austria
172		Linz		Austria
173		Salzburg		Austria
174		Wien		Austria
175		Gomel		Belarus
176		Grodno		Belarus
177		Minsk		Belarus
178		Mogilev		Belarus
179		Vitebsk		Belarus
180		Vychulki, Brest Region, Brest		Belarus
181		Banja Luka		Bosnia and Herzegovina
182		Bihac		Bosnia and Herzegovina
183		Foca		Bosnia and Herzegovina
184		Mostar		Bosnia and Herzegovina
185		Sarajevo		Bosnia and Herzegovina
186		Tuzla		Bosnia and Herzegovina
187		Zenica		Bosnia and Herzegovina
188		Belo Horizonte		Brazil
189		Blumenau		Brazil
190		Brasília		Brazil
191		Campina Grande do Sul		Brazil
192		Campinas		Brazil
193		Canoas		Brazil
194		Curitiba		Brazil
195		Itajaí		Brazil
196		Natal		Brazil
197		Passo Fundo		Brazil
198		Porto Alegre		Brazil
199		Recife		Brazil
200		Ribeirão Preto		Brazil
201		Salvador		Brazil
202		San Paulo		Brazil
203		Santo André		Brazil
204		Sao Paulo		Brazil
205		São José Do Rio Preto		Brazil
206		São Paulo		Brazil
207		Votuporanga		Brazil
208		Blagoevgrad		Bulgaria
209		Burgas		Bulgaria
210		Dimitrovgrad		Bulgaria
211		Gabrovo		Bulgaria
212		Kozlodui		Bulgaria
213		Lom		Bulgaria
214		Lovech		Bulgaria
215		Montana		Bulgaria
216		Pernik		Bulgaria
217		Pleven		Bulgaria
218		Plovdiv		Bulgaria
219		Razlog		Bulgaria
220		Ruse		Bulgaria
221		Sandanski		Bulgaria
222		Sliven		Bulgaria
223		Sofia		Bulgaria
224		Veliko Tarnovo		Bulgaria
225		Vidin		Bulgaria
226		Edmonton	Alberta	Canada
227		Saint John	New Brunswick	Canada
228		Hamilton	Ontario	Canada
229		London	Ontario	Canada
230		Ottawa	Ontario	Canada
231		Scarborough	Ontario	Canada
232		Toronto	Ontario	Canada
233		Waterloo	Ontario	Canada
234		Greenfield Park	Quebec	Canada
235		Montreal	Quebec	Canada
236		Saint-Jerome	Quebec	Canada
237		Sherbrooke	Quebec	Canada
238		Quebec		Canada
239		Armenia		Colombia
240		Barranquilla		Colombia
241		Bogota		Colombia
242		Bogotá		Colombia
243		Cali		Colombia
244		Chia		Colombia
245		Floridablanca		Colombia
246		Medellin		Colombia
247		Medellín		Colombia
248		Villavicencio		Colombia
249		Cakovec		Croatia
250		Karlovac		Croatia
251		Krapinske Toplice		Croatia
252		Osijek		Croatia
253		Pula		Croatia
254		Rijeka		Croatia
255		Sibenik		Croatia
256		Virovitica		Croatia
257		Zabok		Croatia
258		Zadar		Croatia
259		Zagreb		Croatia
260		Boskovice		Czechia
261		Brno		Czechia
262		Cesky Krumlov		Czechia
263		Jablonec Na Nisou		Czechia
264		Karvina		Czechia
265		Kladno		Czechia
266		Krnov		Czechia
267		Kyjov		Czechia
268		Liberec		Czechia
269		Litomysl		Czechia
270		Mestec Kralove		Czechia
271		Nove Mesto na Morave		Czechia
272		Nymburk N/a		Czechia
273		Olomouc		Czechia
274		Opava		Czechia
275		Ostrava		Czechia
276		Pardubice		Czechia
277		Praha 10		Czechia
278		Praha 2		Czechia
279		Praha 4		Czechia
280		Praha 5		Czechia
281		Praha 8		Czechia
282		Pribram		Czechia
283		Písek		Czechia
284		Slany		Czechia
285		Sternberk		Czechia
286		Svitavy		Czechia
287		Teplice		Czechia
288		Trinec		Czechia
289		Trutnov		Czechia
290		Uherske Hradiste		Czechia
291		Usti Nad Labem		Czechia
292		Usti nad Orlici		Czechia
293		Zlin		Czechia
294		Aalborg		Denmark
295		Copenhagen		Denmark
296		Esbjerg		Denmark
297		Frederiksberg		Denmark
298		Hellerup		Denmark
299		Hilleroed		Denmark
300		Hvidovre		Denmark
301		København S		Denmark
302		Roskilde		Denmark
303		Tallinn		Estonia
304		Batumi		Georgia
305		Kutaisi		Georgia
306		Marneuli		Georgia
307		Rustavi		Georgia
308		T'bilisi		Georgia
309		Tbilisi		Georgia
310		Telavi		Georgia
311		Berlin		Germany
312		Coburg		Germany
313		Dresden		Germany
314		Esslingen		Germany
315		Frankfurt		Germany
316		Heidelberg		Germany
317		Jülich		Germany
318		Karlsbad		Germany
319		Leipzig		Germany
320		Limburg		Germany
321		Mannheim		Germany
322		Minden		Germany
323		Mönchengladbach		Germany
324		Neuwied		Germany
325		Troisdorf		Germany
326		Witten		Germany
327		Achaïa		Greece
328		Alexandroupolis		Greece
329		Athens		Greece
330		Heraklion		Greece
331		Ioannina		Greece
332		Kifisia, Athens		Greece
333		Magoula		Greece
334		Patra		Greece
335		Thessalonikis		Greece
336		Thessaloniki		Greece
337		Voula		Greece
338		Ajka		Hungary
339		Baja		Hungary
340		Balassagyarmat		Hungary
341		Berettyóújfalú		Hungary
342		Budapest		Hungary
343		Cegléd		Hungary
344		Debrecen		Hungary
345		Eger		Hungary
346		Farkasgyepü		Hungary
347		Gyula		Hungary
348		Gyõr		Hungary
349		Gödöllő		Hungary
350		Hodmezovasarhely		Hungary
351		Kalocsa		Hungary
352		Kaposvar		Hungary
353		Kecskemet N/a		Hungary
354		Kecskemet		Hungary
355		Keszthely		Hungary
356		Kistarcsa		Hungary
357		Komarom		Hungary
358		Miskolc		Hungary
359		Nagykanizsa		Hungary
360		Orosháza		Hungary
361		Pecs		Hungary
362		Pécs		Hungary
363		Szeged		Hungary
364		Szekesfehervar		Hungary
365		Szekszárd		Hungary
366		Szentes		Hungary
367		Szolnok		Hungary
368		Szombathely		Hungary
369		Székesfehérvár		Hungary
370		Sátoraljaújhely		Hungary
371		Zalaegerszeg		Hungary
372		Beersheba		Israel
373		Hadera		Israel
374		Haifa		Israel
375		Holon		Israel
376		Jerusalem		Israel
377		Kfar-Saba		Israel
378		Modi'in		Israel
379		Nahariya		Israel
380		Petah Tikva		Israel
381		Petah Tiqwa		Israel
382		Rehovot		Israel
383		Safed		Israel
384		Tel-Hashomer		Israel
385		Tiberias		Israel
386		Zefat		Israel
387		Balvi		Latvia
388		Daugavpils		Latvia
389		Jekabpils		Latvia
390		Jelgava		Latvia
391		Krāslavas Apriņķis		Latvia
392		Kuldiga		Latvia
393		Liepaja		Latvia
394		Riga		Latvia
395		Ventspils		Latvia
396		Kaunas		Lithuania
397		Klaipeda		Lithuania
398		Panevezys		Lithuania
399		Siauliai		Lithuania
400		Taurage		Lithuania
401		Utena		Lithuania
402		Vilniaus Apskritis		Lithuania
403		Vilnius		Lithuania
404		Aguascalientes		Mexico
405		Cuernavaca		Mexico
406		Guadalajara		Mexico
407		Merida		Mexico
408		Monterrey		Mexico
409		San Pedro Garza Garcia		Mexico
410		Alkmaar		Netherlands
411		Almelo		Netherlands
412		Amsterdam		Netherlands
413		Arnhem		Netherlands
414		Den Haag		Netherlands
415		Harderwijk		Netherlands
416		Heerlen		Netherlands
417		Hoorn		Netherlands
418		Maastricht		Netherlands
419		Nieuwegein		Netherlands
420		s-Hertogenbosch		Netherlands
421		Sittard-Geleen		Netherlands
422		Sneek		Netherlands
423		Tilburg		Netherlands
424		Veldhoven		Netherlands
425		Zutphen		Netherlands
426		Zwolle		Netherlands
427		Bitola		North Macedonia
428		Ohrid		North Macedonia
429		Skopje		North Macedonia
430		Struga		North Macedonia
431		Štip		North Macedonia
432		Callao		Peru
433		Lima		Peru
434		Bialystok		Poland
435		Bielsko-Biala		Poland
436		Bydgoszcz		Poland
437		Bystra		Poland
438		Czeladz		Poland
439		Gdynia		Poland
440		Kielce		Poland
441		Klodzko		Poland
442		Krakow		Poland
443		Kraków		Poland
444		Leczna		Poland
445		Lodz		Poland
446		Lublin		Poland
447		Olawa		Poland
448		Ostroleka		Poland
449		Ostrow Mazowiecka		Poland
450		Pabianice		Poland
451		Plock		Poland
452		Poznan		Poland
453		Proszowice		Poland
454		Pulawy		Poland
455		Rabka-Zdroj		Poland
456		Siedlce		Poland
457		Sopot,Gdynia		Poland
458		Sosnowiec		Poland
459		Szczecin		Poland
460		Tarn W N/a		Poland
461		Torun		Poland
462		Warszawa N/a		Poland
463		Warszawa		Poland
464		Wegrow		Poland
465		Wroclaw		Poland
466		Braga		Portugal
467		Coimbra		Portugal
468		Covilhã		Portugal
469		Figueira da Foz		Portugal
470		Guimarães		Portugal
471		Lisboa		Portugal
472		Porto		Portugal
473		Vila Nova de Gaia		Portugal
474		San Juan		Puerto Rico
475		Bacau		Romania
476		Baia Mare		Romania
477		Braila		Romania
478		Brasov		Romania
479		Bucuresti		Romania
480		Bucureşti		Romania
481		Cluj-Napoca		Romania
482		Craiova		Romania
483		Focsani		Romania
484		Iasi		Romania
485		Iaşi		Romania
486		Oradea		Romania
487		Pitesti		Romania
488		Tg Mures		Romania
489		Timisoara		Romania
490		Arkhangelsk		Russian Federation
491		Chelyabinsk		Russian Federation
492		Ekaterinburg		Russian Federation
493		Irkutsk		Russian Federation
494		Kazan		Russian Federation
495		Kemerovo		Russian Federation
496		Krasnodar		Russian Federation
497		Krasnoyarsk		Russian Federation
498		Moscow		Russian Federation
499		Moskva		Russian Federation
500		Novosibirsk		Russian Federation
501		Orenburg		Russian Federation
502		Penza		Russian Federation
503		Rostov on Don		Russian Federation
504		Saint Petersburg		Russian Federation
505		Saint-Petersburg		Russian Federation
506		Saratov		Russian Federation
507		Smolensk		Russian Federation
508		St. Petersburg		Russian Federation
509		Tomsk		Russian Federation
510		Ulyanovsk		Russian Federation
511		Vsevolzhsk		Russian Federation
512		Yaroslavl		Russian Federation
513		Belgrade		Serbia
514		Beograd		Serbia
515		Cacak		Serbia
516		Cuprija		Serbia
517		Dedinje		Serbia
518		Kragujevac		Serbia
519		Leskovac		Serbia
520		Nis		Serbia
521		Novi Sad		Serbia
522		Sabac		Serbia
523		Smederevo		Serbia
524		Sremska Kamenica		Serbia
525		Subotica		Serbia
526		Valjevo		Serbia
527		Vranje		Serbia
528		Zaječar		Serbia
529		Kosice		Slovakia
530		Martin		Slovakia
531		Nitra		Slovakia
532		Bellville		South Africa
533		Bloemfontein		South Africa
534		Cape Town		South Africa
535		Durban Kwa Zulu Natal		South Africa
536		Durban		South Africa
537		Gatesville Cape Town		South Africa
538		Groenkloof, Pretoria		South Africa
539		Johannesburg		South Africa
540		Kempton Park		South Africa
541		Kuils River		South Africa
542		Pretoria		South Africa
543		Somerset West		South Africa
544		Stellenbosch		South Africa
545		Worcester		South Africa
546		Alcalá de Henares		Spain
547		Alicante		Spain
548		Almeria		Spain
549		Alzira		Spain
550		Aranjuez		Spain
551		Avila		Spain
552		Balea		Spain
553		Barcelona		Spain
554		Burgos		Spain
555		Cartagena		Spain
556		Cáceres		Spain
557		Don Benito		Spain
558		Elche		Spain
559		Getafe		Spain
560		Granada		Spain
561		Huelva N/a		Spain
562		La Laguna		Spain
563		Las Palmas de Gran Canaria		Spain
564		Logroño		Spain
565		Madrid		Spain
566		Majadahonda-Madrid		Spain
567		Malaga		Spain
568		Murcia		Spain
569		Móstoles		Spain
570		Olot		Spain
571		Oviedo		Spain
572		Palma de Mallorca		Spain
573		Pamplona		Spain
574		Sabadell		Spain
575		San Sebastian de los Reyes		Spain
576		Sanchinarro		Spain
577		Sant Boi de Llobregat		Spain
578		Sant Joan d'Alacant		Spain
579		Santander N/a		Spain
580		Sarrià		Spain
581		Sevilla		Spain
582		Torrelavega Cantabria		Spain
583		Valencia		Spain
584		Zaragoza		Spain
585		Adana		Turkey
586		Ankara		Turkey
587		Antalya		Turkey
588		Istanbul		Turkey
589		Izmir		Turkey
590		Konya		Turkey
591		Rize		Turkey
592		Samsun		Turkey
593		Cherkasy		Ukraine
594		Chernihiv		Ukraine
595		Dnipropetrovsk		Ukraine
596		Ivano-Frankivsky		Ukraine
597		Kharkiv		Ukraine
598		Kherson		Ukraine
599		Kyiv		Ukraine
600		Lutsk		Ukraine
601		Lviv		Ukraine
602		Odessa		Ukraine
603		Poltava		Ukraine
604		Sumy		Ukraine
605		Uzhgorod		Ukraine
606		Vinnytsia		Ukraine
607		Zaporizhzhia		Ukraine
608		Zaporizhzhya		Ukraine
609		Zhytomyr		Ukraine
610		Angus		United Kingdom
611		Cardiff		United Kingdom
612		Craigavon		United Kingdom
613		Glasgow		United Kingdom
614		Leeds		United Kingdom
615		Manchester		United Kingdom
616		Norwich		United Kingdom
617		Plymouth		United Kingdom

Sponsors and Collaborators

• Janssen Research & Development, LLC
• Bayer

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Study Protocol - Mar 31, 2017
• Statistical Analysis Plan - Apr 4, 2017

More Information

Publications

• Raskob GE, Spyropoulos AC, Zrubek J, Ageno W, Albers G, Elliott CG, Halperin J, Haskell L, Hiatt WR, Maynard GA, Peters G, Spiro T, Steg PG, Suh EY, Weitz JI. The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE. Design, rationale, and clinical implications. Thromb Haemost. 2016 Jun 2;115(6):1240-8. doi: 10.1160/TH15-09-0756. Epub 2016 Feb 4.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02111564
• Other Study ID Numbers: CR103834; 2014-000305-13; RIVAROXDVT3002
• First Posted: Apr 11, 2014
• Last Update Posted: Nov 25, 2019
• Last Verified: Nov 1, 2019

• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Research & Development, LLC: Heart Failure; Respiratory Insufficiency; Stroke Acute; Infectious Diseases; Rheumatic Diseases; Medically ill Patient; Rivaroxaban; Thromboembolism; Prophylactic Anti-Coagulation
• Additional relevant MeSH terms: Communicable Diseases; Infections; Rheumatic Diseases; Respiratory Insufficiency; Heart Failure; Collagen Diseases; Rivaroxaban

Study Results

Participant Flow

Recruitment Details	12024 participants were randomized (rivaroxaban-6007;placebo-6017). 5 participants in placebo were excluded(2 invalid consent,3 randomized before Health Authority approval).
Pre-assignment Detail	Participants were randomized (1:1) to receive rivaroxaban or placebo. In rivaroxaban, participants were treated with rivaroxaban 10 mg or 7.5 mg as per their creatinine clearance level. Data in the participant flow section is reported for study discontinuation from the disposition data.

Arm/Group Title	Rivaroxaban 10 mg or 7.5 mg	Placebo
Arm/Group Description	Participants with a creatinine clearance (CrCl) greater than or equal to (>=) 50 milliliter per minute (mL/min) received 10 milligram (mg) rivaroxaban tablet once daily orally and participants with a creatinine clearance from >=30 to less than (<) 50 mL/min at screening received 7.5 mg rivaroxaban tablet once daily orally for 45 days.	Participants received rivaroxaban matched placebo tablet once daily orally for 45 days.
Period Title: Overall Study
STARTED	6007	6012
Treated	5982	5980
COMPLETED	5876	5869
NOT COMPLETED	131	143

Baseline Characteristics

Arm/Group Title	Rivaroxaban 10 mg or 7.5 mg	Placebo	Total
Arm/Group Description	Participants with a creatinine clearance (CrCl) greater than or equal to (>=) 50 milliliter per minute (mL/min) received 10 milligram (mg) rivaroxaban tablet once daily orally and participants with a creatinine clearance from >=30 to less than (<) 50 mL/min at screening received 7.5 mg rivaroxaban tablet once daily orally for 45 days.	Participants received rivaroxaban matched placebo tablet once daily orally for 45 days.	Total of all reporting groups
Overall Participants	6007	6012	12019
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.7 (10.06)	69.7 (10.22)	69.7 (10.14)
Sex: Female, Male (Count of Participants)
Female	2877 47.9%	2858 47.5%	5735 47.7%
Male	3130 52.1%	3154 52.5%	6284 52.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	499 8.3%	482 8%	981 8.2%
Not Hispanic or Latino	5490 91.4%	5510 91.7%	11000 91.5%
Unknown or Not Reported	18 0.3%	20 0.3%	38 0.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	9 0.1%	5 0.1%	14 0.1%
Asian	8 0.1%	8 0.1%	16 0.1%
Native Hawaiian or Other Pacific Islander	128 2.1%	123 2%	251 2.1%
Black or African American	71 1.2%	57 0.9%	128 1.1%
White	5782 96.3%	5808 96.6%	11590 96.4%
More than one race	6 0.1%	9 0.1%	15 0.1%
Unknown or Not Reported	3 0%	2 0%	5 0%
Region of Enrollment (Count of Participants)
ARGENTINA	120 2%	122 2%	242 2%
AUSTRALIA	45 0.7%	43 0.7%	88 0.7%
AUSTRIA	6 0.1%	8 0.1%	14 0.1%
BELARUS	67 1.1%	66 1.1%	133 1.1%
BOSNIA-HERZEGOVINA	298 5%	299 5%	597 5%
BRAZIL	46 0.8%	46 0.8%	92 0.8%
BULGARIA	714 11.9%	714 11.9%	1428 11.9%
CANADA	21 0.3%	22 0.4%	43 0.4%
COLOMBIA	70 1.2%	70 1.2%	140 1.2%
CROATIA	135 2.2%	135 2.2%	270 2.2%
CZECH REPUBLIC	115 1.9%	116 1.9%	231 1.9%
DENMARK	3 0%	4 0.1%	7 0.1%
ESTONIA	5 0.1%	6 0.1%	11 0.1%
GEORGIA	880 14.6%	882 14.7%	1762 14.7%
GERMANY	8 0.1%	9 0.1%	17 0.1%
GREECE	66 1.1%	65 1.1%	131 1.1%
HUNGARY	275 4.6%	274 4.6%	549 4.6%
ISRAEL	55 0.9%	56 0.9%	111 0.9%
ITALY	74 1.2%	73 1.2%	147 1.2%
LATVIA	154 2.6%	154 2.6%	308 2.6%
LITHUANIA	82 1.4%	82 1.4%	164 1.4%
MEXICO	17 0.3%	15 0.2%	32 0.3%
NETHERLANDS	8 0.1%	9 0.1%	17 0.1%
PERU	33 0.5%	32 0.5%	65 0.5%
POLAND	310 5.2%	309 5.1%	619 5.2%
PORTUGAL	6 0.1%	7 0.1%	13 0.1%
PUERTO RICO	0 0%	1 0%	1 0%
REPUBLIC OF MACEDONIA	451 7.5%	451 7.5%	902 7.5%
ROMANIA	162 2.7%	162 2.7%	324 2.7%
RUSSIAN FEDERATION	571 9.5%	571 9.5%	1142 9.5%
SERBIA	305 5.1%	304 5.1%	609 5.1%
SOUTH AFRICA	103 1.7%	102 1.7%	205 1.7%
SPAIN	192 3.2%	191 3.2%	383 3.2%
TURKEY	35 0.6%	35 0.6%	70 0.6%
UKRAINE	426 7.1%	428 7.1%	854 7.1%
UNITED KINGDOM	4 0.1%	4 0.1%	8 0.1%
UNITED STATES	145 2.4%	145 2.4%	290 2.4%

Outcome Measures

1. Primary Outcome

Title	Time From Randomization to First Occurrence of Composite of All Symptomatic Venous Thromboembolism (VTE) and VTE Related Death Adjudicated by Clinical Event Committee (CEC)
Description	Symptomatic VTE included lower extremity deep vein thrombosis (DVT) and non-fatal pulmonary embolism (PE). Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.
Time Frame	Up to Day 45

Outcome Measure Data

Analysis Population Description

Intention-to-treat (ITT) analysis set comprised all randomized participants who signed a valid informed consent, regardless of actual treatment received.

Arm/Group Title	Rivaroxaban 10 mg or 7.5 mg	Placebo
Arm/Group Description	Participants with a creatinine clearance (CrCl) greater than or equal to (>=) 50 milliliter per minute (mL/min) received 10 milligram (mg) rivaroxaban tablet once daily orally and participants with a creatinine clearance from >=30 to less than (<) 50 mL/min at screening received 7.5 mg rivaroxaban tablet once daily orally for 45 days.	Participants received rivaroxaban matched placebo tablet once daily orally for 45 days.
Measure Participants	6007	6012
Number [Events per 100 participants in 45 days]	0.84 0%	1.11 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban 10 mg or 7.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.136
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Event Rate Based on Time From Randomization to the First Occurrence of Major Bleeding Adjudicated by CEC
Description	A major bleeding event was defined using validated International Society on Thrombosis and Haemostasis (ISTH) bleeding criteria. A major bleeding event was defined as overt bleeding that was associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or a critical site defined as intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or a fatal outcome. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or last dose + 2 days.
Time Frame	From randomization to 2 days after the last dose (Day 45)

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all enrolled participants in the ITT analysis set who received at least 1 dose of study drug.

Arm/Group Title	Rivaroxaban 10 mg or 7.5 mg	Placebo
Arm/Group Description	Participants with a creatinine clearance (CrCl) greater than or equal to (>=) 50 milliliter per minute (mL/min) received 10 milligram (mg) rivaroxaban tablet once daily orally and participants with a creatinine clearance from >=30 to less than (<) 50 mL/min at screening received 7.5 mg rivaroxaban tablet once daily orally for 45 days.	Participants received rivaroxaban matched placebo tablet once daily orally for 45 days.
Measure Participants	5982	5980
Number [Events per 100 participants in 45 days]	0.28 0%	0.15 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban 10 mg or 7.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.124
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.88
	Confidence Interval	(2-Sided) 95%; 0.84 to 4.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Event Rate Based on Time From Randomization to First Occurrence of VTE-Related Death Adjudicated by CEC
Description	Event rate based on time from randomization to first occurrence of VTE-related death (adjudicated by CEC) was assessed. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.
Time Frame	Up to Day 45

Outcome Measure Data

Analysis Population Description

ITT analysis set comprised all randomized participants who signed a valid informed consent, regardless of actual treatment received.

Arm/Group Title	Rivaroxaban 10 mg or 7.5 mg	Placebo
Arm/Group Description	Participants with a creatinine clearance (CrCl) greater than or equal to (>=) 50 milliliter per minute (mL/min) received 10 milligram (mg) rivaroxaban tablet once daily orally and participants with a creatinine clearance from >=30 to less than (<) 50 mL/min at screening received 7.5 mg rivaroxaban tablet once daily orally for 45 days.	Participants received rivaroxaban matched placebo tablet once daily orally for 45 days.
Measure Participants	6007	6012
Number [Events per 100 participants in 45 days]	0.72 0%	0.77 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban 10 mg or 7.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.751
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Event Rate Based on Time From Randomization to the First Occurrence of a Symptomatic Venous Thromboembolism Event (VTE) Adjudicated by CEC
Description	Event rate based on time from randomization to the first occurrence of a symptomatic VTE (adjudicated by CEC) was assessed. Symptomatic VTE included lower extremity DVT and non-fatal PE. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.
Time Frame	Up to Day 45

Outcome Measure Data

Analysis Population Description

ITT analysis set comprised all randomized participants who signed a valid informed consent, regardless of actual treatment received.

Arm/Group Title	Rivaroxaban 10 mg or 7.5 mg	Placebo
Arm/Group Description	Participants with a creatinine clearance (CrCl) greater than or equal to (>=) 50 milliliter per minute (mL/min) received 10 milligram (mg) rivaroxaban tablet once daily orally and participants with a creatinine clearance from >=30 to less than (<) 50 mL/min at screening received 7.5 mg rivaroxaban tablet once daily orally for 45 days.	Participants received rivaroxaban matched placebo tablet once daily orally for 45 days.
Measure Participants	6007	6012
Number [Events per 100 participants in 45 days]	0.19 0%	0.42 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban 10 mg or 7.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.023
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; 0.22 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Event Rate Based on Time From Randomization to the First Occurrence of a Composite of Symptomatic VTE and All-Cause Mortality (ACM) Adjudicated by CEC
Description	Event rate based on time from randomization to the first occurrence of a composite of symptomatic VTE and ACM (adjudicated by CEC) was assessed. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.
Time Frame	Up to Day 45

Outcome Measure Data

Analysis Population Description

ITT analysis set comprised all randomized participants who signed a valid informed consent, regardless of actual treatment received.

Arm/Group Title	Rivaroxaban 10 mg or 7.5 mg	Placebo
Arm/Group Description	Participants with a creatinine clearance (CrCl) greater than or equal to (>=) 50 milliliter per minute (mL/min) received 10 milligram (mg) rivaroxaban tablet once daily orally and participants with a creatinine clearance from >=30 to less than (<) 50 mL/min at screening received 7.5 mg rivaroxaban tablet once daily orally for 45 days.	Participants received rivaroxaban matched placebo tablet once daily orally for 45 days.
Measure Participants	6007	6012
Number [Events per 100 participants in 45 days]	1.31 0%	1.80 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban 10 mg or 7.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.033
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.54 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Event Rate Based on Time From Randomization to the First Occurrence of a Composite of Symptomatic VTE, Myocardial Infarction (MI), Non-Hemorrhagic Stroke, and Cardiovascular (CV) Death Adjudicated by CEC
Description	Event rate based on time from randomization to the first occurrence of a composite of symptomatic VTE (lower extremity DVT and non-fatal PE), MI, non-hemorrhagic stroke, and CV death (death due to a known CV cause and death in which a CV cause cannot be ruled out; by this definition, a VTE-related death was considered a CV death) as adjudicated by CEC was reported. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.
Time Frame	Up to Day 45

Outcome Measure Data

Analysis Population Description

ITT analysis set comprised all randomized participants who signed a valid informed consent, regardless of actual treatment received.

Arm/Group Title	Rivaroxaban 10 mg or 7.5 mg	Placebo
Arm/Group Description	Participants with a creatinine clearance (CrCl) greater than or equal to (>=) 50 milliliter per minute (mL/min) received 10 milligram (mg) rivaroxaban tablet once daily orally and participants with a creatinine clearance from >=30 to less than (<) 50 mL/min at screening received 7.5 mg rivaroxaban tablet once daily orally for 45 days.	Participants received rivaroxaban matched placebo tablet once daily orally for 45 days.
Measure Participants	6007	6012
Number [Events per 100 participants in 45 days]	1.58 0%	2.03 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban 10 mg or 7.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.073
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Event Rate Based on Time From Randomization to First Occurrence of All-Cause Mortality (ACM) Adjudicated by CEC
Description	Event rate based on time from randomization to first occurrence of ACM (adjudicated by CEC) was assessed. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.
Time Frame	Up to Day 45

Outcome Measure Data

Analysis Population Description

ITT analysis set comprised all randomized participants who signed a valid informed consent, regardless of actual treatment received.

Arm/Group Title	Rivaroxaban 10 mg or 7.5 mg	Placebo
Arm/Group Description	Participants with a creatinine clearance (CrCl) greater than or equal to (>=) 50 milliliter per minute (mL/min) received 10 milligram (mg) rivaroxaban tablet once daily orally and participants with a creatinine clearance from >=30 to less than (<) 50 mL/min at screening received 7.5 mg rivaroxaban tablet once daily orally for 45 days.	Participants received rivaroxaban matched placebo tablet once daily orally for 45 days.
Measure Participants	6007	6012
Number [Events per 100 participants in 45 days]	1.19 0%	1.49 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rivaroxaban 10 mg or 7.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.156
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.58 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Up to 75 days (+/-5 days)
Adverse Event Reporting Description	Intention-to-treat (ITT) analysis set comprised all randomized participants who signed a valid informed consent, regardless of actual treatment received.
Arm/Group Title	Rivaroxaban 10 mg or 7.5 mg		Placebo
Arm/Group Description	Participants with a creatinine clearance (CrCl) greater than or equal to (>=) 50 milliliter per minute (mL/min) received 10 milligram (mg) rivaroxaban tablet once daily orally and participants with a creatinine clearance from >=30 to less than (<) 50 mL/min at screening received 7.5 mg rivaroxaban tablet once daily orally for 45 days.		Participants received rivaroxaban matched placebo tablet once daily orally for 45 days.
All Cause Mortality
	Rivaroxaban 10 mg or 7.5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/6007 (1.9%)		126/6012 (2.1%)
Serious Adverse Events
	Rivaroxaban 10 mg or 7.5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	475/6007 (7.9%)		493/6012 (8.2%)
Blood and lymphatic system disorders
Anaemia	3/6007 (0%)		0/6012 (0%)
Autoimmune Haemolytic Anaemia	1/6007 (0%)		0/6012 (0%)
Haemorrhagic Anaemia	1/6007 (0%)		0/6012 (0%)
Iron Deficiency Anaemia	1/6007 (0%)		0/6012 (0%)
Thrombocytopenia	0/6007 (0%)		1/6012 (0%)
Cardiac disorders
Acute Left Ventricular Failure	1/6007 (0%)		1/6012 (0%)
Angina Pectoris	3/6007 (0%)		1/6012 (0%)
Aortic Valve Incompetence	1/6007 (0%)		0/6012 (0%)
Atrial Fibrillation	13/6007 (0.2%)		10/6012 (0.2%)
Atrial Flutter	3/6007 (0%)		6/6012 (0.1%)
Atrioventricular Block Complete	4/6007 (0.1%)		1/6012 (0%)
Atrioventricular Block Second Degree	1/6007 (0%)		1/6012 (0%)
Bradyarrhythmia	1/6007 (0%)		0/6012 (0%)
Bradycardia	0/6007 (0%)		2/6012 (0%)
Cardiac Arrest	5/6007 (0.1%)		5/6012 (0.1%)
Cardiac Asthma	1/6007 (0%)		0/6012 (0%)
Cardiac Failure	51/6007 (0.8%)		62/6012 (1%)
Cardiac Failure Acute	14/6007 (0.2%)		14/6012 (0.2%)
Cardiac Failure Chronic	13/6007 (0.2%)		8/6012 (0.1%)
Cardiac Failure Congestive	24/6007 (0.4%)		25/6012 (0.4%)
Cardiac Valve Disease	1/6007 (0%)		1/6012 (0%)
Cardiac Ventricular Thrombosis	1/6007 (0%)		0/6012 (0%)
Cardio-Respiratory Arrest	5/6007 (0.1%)		2/6012 (0%)
Cardiogenic Shock	4/6007 (0.1%)		2/6012 (0%)
Cardiomyopathy	2/6007 (0%)		1/6012 (0%)
Cardiomyopathy Acute	0/6007 (0%)		1/6012 (0%)
Cardiopulmonary Failure	4/6007 (0.1%)		4/6012 (0.1%)
Congestive Cardiomyopathy	1/6007 (0%)		2/6012 (0%)
Cor Pulmonale	0/6007 (0%)		1/6012 (0%)
Coronary Artery Disease	1/6007 (0%)		0/6012 (0%)
Coronary Artery Stenosis	1/6007 (0%)		0/6012 (0%)
Diastolic Dysfunction	1/6007 (0%)		0/6012 (0%)
Hypertensive Heart Disease	0/6007 (0%)		1/6012 (0%)
Interventricular Septum Rupture	0/6007 (0%)		1/6012 (0%)
Ischaemic Cardiomyopathy	1/6007 (0%)		1/6012 (0%)
Left Ventricular Failure	4/6007 (0.1%)		2/6012 (0%)
Mitral Valve Incompetence	1/6007 (0%)		0/6012 (0%)
Myocardial Fibrosis	2/6007 (0%)		0/6012 (0%)
Myocardial Ischaemia	1/6007 (0%)		1/6012 (0%)
Myocarditis	0/6007 (0%)		1/6012 (0%)
Nodal Rhythm	1/6007 (0%)		0/6012 (0%)
Pericarditis	1/6007 (0%)		1/6012 (0%)
Right Ventricular Failure	1/6007 (0%)		0/6012 (0%)
Sinus Bradycardia	1/6007 (0%)		1/6012 (0%)
Sinus Node Dysfunction	2/6007 (0%)		1/6012 (0%)
Supraventricular Tachycardia	1/6007 (0%)		3/6012 (0%)
Tachycardia	0/6007 (0%)		1/6012 (0%)
Ventricular Extrasystoles	0/6007 (0%)		2/6012 (0%)
Ventricular Tachycardia	3/6007 (0%)		0/6012 (0%)
Ear and labyrinth disorders
Motion Sickness	0/6007 (0%)		1/6012 (0%)
Vertigo	2/6007 (0%)		0/6012 (0%)
Vertigo Positional	1/6007 (0%)		0/6012 (0%)
Eye disorders
Conjunctival Oedema	1/6007 (0%)		0/6012 (0%)
Exophthalmos	1/6007 (0%)		0/6012 (0%)
Retinal Artery Occlusion	0/6007 (0%)		1/6012 (0%)
Gastrointestinal disorders
Abdominal Incarcerated Hernia	0/6007 (0%)		1/6012 (0%)
Abdominal Pain	1/6007 (0%)		1/6012 (0%)
Acute Abdomen	0/6007 (0%)		1/6012 (0%)
Ascites	0/6007 (0%)		1/6012 (0%)
Chronic Gastritis	1/6007 (0%)		0/6012 (0%)
Colitis Ischaemic	1/6007 (0%)		1/6012 (0%)
Diarrhoea	3/6007 (0%)		0/6012 (0%)
Duodenal Ulcer	2/6007 (0%)		2/6012 (0%)
Dyspepsia	0/6007 (0%)		1/6012 (0%)
Dysphagia	1/6007 (0%)		0/6012 (0%)
Enterocolitis	2/6007 (0%)		2/6012 (0%)
Enterocolitis Haemorrhagic	0/6007 (0%)		1/6012 (0%)
Enterovesical Fistula	0/6007 (0%)		1/6012 (0%)
Gastric Polyps	1/6007 (0%)		0/6012 (0%)
Gastric Ulcer	0/6007 (0%)		1/6012 (0%)
Gastritis	1/6007 (0%)		0/6012 (0%)
Gastrooesophageal Reflux Disease	1/6007 (0%)		1/6012 (0%)
Haemorrhoids	0/6007 (0%)		1/6012 (0%)
Ileus	1/6007 (0%)		1/6012 (0%)
Inguinal Hernia	1/6007 (0%)		0/6012 (0%)
Intestinal Ischaemia	0/6007 (0%)		1/6012 (0%)
Pancreatic Disorder	0/6007 (0%)		1/6012 (0%)
Pancreatitis	0/6007 (0%)		1/6012 (0%)
Pancreatitis Acute	2/6007 (0%)		2/6012 (0%)
Peptic Ulcer	0/6007 (0%)		1/6012 (0%)
Peptic Ulcer Haemorrhage	1/6007 (0%)		0/6012 (0%)
Peptic Ulcer Perforation	1/6007 (0%)		0/6012 (0%)
Rectal Polyp	0/6007 (0%)		1/6012 (0%)
Small Intestinal Obstruction	0/6007 (0%)		2/6012 (0%)
Subileus	0/6007 (0%)		1/6012 (0%)
Vomiting	0/6007 (0%)		1/6012 (0%)
General disorders
Asthenia	1/6007 (0%)		1/6012 (0%)
Chest Pain	0/6007 (0%)		1/6012 (0%)
Death	25/6007 (0.4%)		30/6012 (0.5%)
Fatigue	1/6007 (0%)		2/6012 (0%)
Multiple Organ Dysfunction Syndrome	1/6007 (0%)		2/6012 (0%)
Oedema Peripheral	1/6007 (0%)		1/6012 (0%)
Peripheral Swelling	1/6007 (0%)		0/6012 (0%)
Pyrexia	0/6007 (0%)		3/6012 (0%)
Sudden Cardiac Death	1/6007 (0%)		2/6012 (0%)
Systemic Inflammatory Response Syndrome	1/6007 (0%)		0/6012 (0%)
Hepatobiliary disorders
Bile Duct Obstruction	0/6007 (0%)		1/6012 (0%)
Bile Duct Stone	0/6007 (0%)		2/6012 (0%)
Cholecystitis	2/6007 (0%)		3/6012 (0%)
Cholecystitis Acute	2/6007 (0%)		0/6012 (0%)
Cholecystitis Chronic	1/6007 (0%)		0/6012 (0%)
Cholelithiasis	2/6007 (0%)		2/6012 (0%)
Hepatic Lesion	0/6007 (0%)		1/6012 (0%)
Immune system disorders
Anaphylactic Reaction	1/6007 (0%)		0/6012 (0%)
Infections and infestations
Abdominal Abscess	0/6007 (0%)		1/6012 (0%)
Abscess Limb	0/6007 (0%)		1/6012 (0%)
Anal Abscess	0/6007 (0%)		1/6012 (0%)
Breast Cellulitis	0/6007 (0%)		1/6012 (0%)
Bronchitis	5/6007 (0.1%)		3/6012 (0%)
Bronchopulmonary Aspergillosis	0/6007 (0%)		1/6012 (0%)
Cellulitis	11/6007 (0.2%)		10/6012 (0.2%)
Clostridium Difficile Colitis	2/6007 (0%)		1/6012 (0%)
Clostridium Difficile Infection	1/6007 (0%)		1/6012 (0%)
Diabetic Foot Infection	0/6007 (0%)		1/6012 (0%)
Diverticulitis	0/6007 (0%)		1/6012 (0%)
Empyema	0/6007 (0%)		1/6012 (0%)
Endocarditis	0/6007 (0%)		2/6012 (0%)
Endocarditis Bacterial	0/6007 (0%)		1/6012 (0%)
Endophthalmitis	0/6007 (0%)		1/6012 (0%)
Endotoxic Shock	0/6007 (0%)		1/6012 (0%)
Erysipelas	3/6007 (0%)		4/6012 (0.1%)
Fungal Oesophagitis	1/6007 (0%)		0/6012 (0%)
Fungal Skin Infection	1/6007 (0%)		0/6012 (0%)
Gastroenteritis	2/6007 (0%)		3/6012 (0%)
Gastroenteritis Salmonella	1/6007 (0%)		0/6012 (0%)
Gastroenteritis Viral	0/6007 (0%)		1/6012 (0%)
Haematoma Infection	0/6007 (0%)		1/6012 (0%)
Helicobacter Infection	0/6007 (0%)		1/6012 (0%)
Infection	1/6007 (0%)		0/6012 (0%)
Infectious Colitis	0/6007 (0%)		1/6012 (0%)
Infectious Pleural Effusion	1/6007 (0%)		0/6012 (0%)
Infective Exacerbation of Bronchiectasis	1/6007 (0%)		0/6012 (0%)
Infective Exacerbation of Chronic Obstructive Airways Disease	1/6007 (0%)		4/6012 (0.1%)
Infective Spondylitis	1/6007 (0%)		0/6012 (0%)
Influenza	1/6007 (0%)		1/6012 (0%)
Injection Site Abscess	1/6007 (0%)		0/6012 (0%)
Intervertebral Discitis	0/6007 (0%)		2/6012 (0%)
Lower Respiratory Tract Infection	2/6007 (0%)		1/6012 (0%)
Lung Abscess	0/6007 (0%)		1/6012 (0%)
Lung Infection	0/6007 (0%)		1/6012 (0%)
Mediastinitis	0/6007 (0%)		1/6012 (0%)
Osteomyelitis	0/6007 (0%)		1/6012 (0%)
Parotitis	0/6007 (0%)		1/6012 (0%)
Pneumonia	58/6007 (1%)		48/6012 (0.8%)
Pneumonia Bacterial	2/6007 (0%)		4/6012 (0.1%)
Pneumonia Pseudomonal	0/6007 (0%)		1/6012 (0%)
Pneumonia Staphylococcal	0/6007 (0%)		1/6012 (0%)
Postoperative Wound Infection	0/6007 (0%)		1/6012 (0%)
Pulmonary Sepsis	0/6007 (0%)		2/6012 (0%)
Pulmonary Tuberculosis	1/6007 (0%)		0/6012 (0%)
Pyelonephritis	0/6007 (0%)		2/6012 (0%)
Pyelonephritis Chronic	2/6007 (0%)		1/6012 (0%)
Pyoderma	0/6007 (0%)		1/6012 (0%)
Respiratory Tract Infection	3/6007 (0%)		3/6012 (0%)
Sepsis	4/6007 (0.1%)		3/6012 (0%)
Septic Shock	1/6007 (0%)		4/6012 (0.1%)
Sinusitis	1/6007 (0%)		0/6012 (0%)
Soft Tissue Infection	0/6007 (0%)		1/6012 (0%)
Splenic Abscess	0/6007 (0%)		1/6012 (0%)
Staphylococcal Bacteraemia	1/6007 (0%)		0/6012 (0%)
Staphylococcal Sepsis	2/6007 (0%)		0/6012 (0%)
Systemic Infection	1/6007 (0%)		0/6012 (0%)
Tracheobronchitis	2/6007 (0%)		0/6012 (0%)
Tuberculous Pleurisy	0/6007 (0%)		1/6012 (0%)
Upper Respiratory Tract Infection	2/6007 (0%)		1/6012 (0%)
Urinary Tract Infection	11/6007 (0.2%)		11/6012 (0.2%)
Urinary Tract Infection Bacterial	1/6007 (0%)		0/6012 (0%)
Urosepsis	0/6007 (0%)		4/6012 (0.1%)
Viral Infection	1/6007 (0%)		0/6012 (0%)
Wound Infection	1/6007 (0%)		0/6012 (0%)
Wound Infection Staphylococcal	1/6007 (0%)		0/6012 (0%)
Injury, poisoning and procedural complications
Accidental Overdose	1/6007 (0%)		0/6012 (0%)
Cervical Vertebral Fracture	1/6007 (0%)		0/6012 (0%)
Fall	1/6007 (0%)		1/6012 (0%)
Femoral Neck Fracture	0/6007 (0%)		2/6012 (0%)
Femur Fracture	0/6007 (0%)		3/6012 (0%)
Head Injury	1/6007 (0%)		2/6012 (0%)
Hip Fracture	1/6007 (0%)		2/6012 (0%)
Humerus Fracture	0/6007 (0%)		1/6012 (0%)
Intestinal Anastomosis Complication	0/6007 (0%)		1/6012 (0%)
Laceration	0/6007 (0%)		1/6012 (0%)
Ligament Rupture	1/6007 (0%)		1/6012 (0%)
Lower Limb Fracture	1/6007 (0%)		1/6012 (0%)
Lumbar Vertebral Fracture	0/6007 (0%)		1/6012 (0%)
Multiple Injuries	0/6007 (0%)		1/6012 (0%)
Nerve Injury	1/6007 (0%)		0/6012 (0%)
Procedural Pneumothorax	1/6007 (0%)		0/6012 (0%)
Rib Fracture	1/6007 (0%)		1/6012 (0%)
Soft Tissue Injury	1/6007 (0%)		0/6012 (0%)
Tendon Injury	0/6007 (0%)		1/6012 (0%)
Toxicity to Various Agents	0/6007 (0%)		1/6012 (0%)
Traumatic Lung Injury	0/6007 (0%)		1/6012 (0%)
Twiddler's Syndrome	0/6007 (0%)		1/6012 (0%)
Investigations
Aspiration Bronchial	1/6007 (0%)		0/6012 (0%)
Body Temperature Increased	0/6007 (0%)		2/6012 (0%)
Cardiac Output Decreased	1/6007 (0%)		0/6012 (0%)
Myocardial Necrosis Marker Increased	0/6007 (0%)		1/6012 (0%)
Metabolism and nutrition disorders
Dehydration	2/6007 (0%)		3/6012 (0%)
Diabetes Mellitus	1/6007 (0%)		0/6012 (0%)
Diabetes Mellitus Inadequate Control	1/6007 (0%)		1/6012 (0%)
Diabetic Metabolic Decompensation	1/6007 (0%)		0/6012 (0%)
Failure to Thrive	1/6007 (0%)		0/6012 (0%)
Fluid Overload	0/6007 (0%)		1/6012 (0%)
Gout	1/6007 (0%)		2/6012 (0%)
Hyperglycaemia	2/6007 (0%)		0/6012 (0%)
Hyperkalaemia	1/6007 (0%)		0/6012 (0%)
Hypoalbuminaemia	1/6007 (0%)		0/6012 (0%)
Hypocalcaemia	0/6007 (0%)		1/6012 (0%)
Hypoglycaemia	3/6007 (0%)		5/6012 (0.1%)
Hypokalaemia	0/6007 (0%)		1/6012 (0%)
Hyponatraemia	1/6007 (0%)		1/6012 (0%)
Overweight	0/6007 (0%)		1/6012 (0%)
Type 2 Diabetes Mellitus	0/6007 (0%)		1/6012 (0%)
Vitamin B12 Deficiency	1/6007 (0%)		0/6012 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	0/6007 (0%)		1/6012 (0%)
Back Pain	1/6007 (0%)		1/6012 (0%)
Bursitis	0/6007 (0%)		1/6012 (0%)
Compartment Syndrome	1/6007 (0%)		0/6012 (0%)
Musculoskeletal Chest Pain	2/6007 (0%)		0/6012 (0%)
Osteoarthritis	2/6007 (0%)		1/6012 (0%)
Rheumatoid Arthritis	1/6007 (0%)		3/6012 (0%)
Vertebral Lesion	0/6007 (0%)		1/6012 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Leukaemia	1/6007 (0%)		0/6012 (0%)
Adenocarcinoma	1/6007 (0%)		0/6012 (0%)
Adenocarcinoma of Colon	1/6007 (0%)		0/6012 (0%)
Bladder Cancer Recurrent	1/6007 (0%)		0/6012 (0%)
Bladder Neoplasm	0/6007 (0%)		2/6012 (0%)
Breast Cancer	1/6007 (0%)		1/6012 (0%)
Breast Neoplasm	1/6007 (0%)		0/6012 (0%)
Colon Cancer Metastatic	1/6007 (0%)		0/6012 (0%)
Gastric Cancer	1/6007 (0%)		0/6012 (0%)
Hepatic Cancer Metastatic	1/6007 (0%)		0/6012 (0%)
Invasive Ductal Breast Carcinoma	1/6007 (0%)		0/6012 (0%)
Lung Cancer Metastatic	0/6007 (0%)		2/6012 (0%)
Lung Infiltration Malignant	1/6007 (0%)		0/6012 (0%)
Lung Neoplasm	2/6007 (0%)		1/6012 (0%)
Lung Neoplasm Malignant	0/6007 (0%)		5/6012 (0.1%)
Malignant Neoplasm of Unknown Primary Site	0/6007 (0%)		1/6012 (0%)
Malignant Pleural Effusion	0/6007 (0%)		1/6012 (0%)
Mediastinum Neoplasm	1/6007 (0%)		0/6012 (0%)
Meningioma	1/6007 (0%)		0/6012 (0%)
Metastatic Neoplasm	0/6007 (0%)		1/6012 (0%)
Non-Hodgkin's Lymphoma	1/6007 (0%)		0/6012 (0%)
Non-Small Cell Lung Cancer	0/6007 (0%)		1/6012 (0%)
Ovarian Cancer	0/6007 (0%)		1/6012 (0%)
Plasma Cell Myeloma	0/6007 (0%)		1/6012 (0%)
Rectal Cancer	0/6007 (0%)		1/6012 (0%)
Rectal Neoplasm	0/6007 (0%)		1/6012 (0%)
Rectosigmoid Cancer	1/6007 (0%)		0/6012 (0%)
Renal Neoplasm	1/6007 (0%)		0/6012 (0%)
Squamous Cell Carcinoma of Lung	1/6007 (0%)		1/6012 (0%)
Nervous system disorders
Aphasia	1/6007 (0%)		0/6012 (0%)
Carotid Artery Occlusion	1/6007 (0%)		1/6012 (0%)
Carotid Artery Stenosis	1/6007 (0%)		0/6012 (0%)
Craniocervical Syndrome	1/6007 (0%)		0/6012 (0%)
Demyelinating Polyneuropathy	1/6007 (0%)		0/6012 (0%)
Encephalopathy	1/6007 (0%)		0/6012 (0%)
Epilepsy	1/6007 (0%)		1/6012 (0%)
Facial Paralysis	1/6007 (0%)		0/6012 (0%)
Headache	2/6007 (0%)		0/6012 (0%)
Hypoglycaemic Coma	1/6007 (0%)		0/6012 (0%)
Hypoglycaemic Encephalopathy	0/6007 (0%)		1/6012 (0%)
Ischaemic Stroke	0/6007 (0%)		1/6012 (0%)
Lumbar Radiculopathy	0/6007 (0%)		1/6012 (0%)
Orthostatic Intolerance	0/6007 (0%)		1/6012 (0%)
Presyncope	1/6007 (0%)		0/6012 (0%)
Sciatica	1/6007 (0%)		1/6012 (0%)
Seizure	1/6007 (0%)		0/6012 (0%)
Syncope	6/6007 (0.1%)		5/6012 (0.1%)
Vascular Encephalopathy	0/6007 (0%)		1/6012 (0%)
Vertebral Artery Stenosis	1/6007 (0%)		0/6012 (0%)
Vertigo CNS Origin	1/6007 (0%)		0/6012 (0%)
Product Issues
Device Dislocation	0/6007 (0%)		1/6012 (0%)
Device Failure	1/6007 (0%)		0/6012 (0%)
Device Occlusion	1/6007 (0%)		0/6012 (0%)
Psychiatric disorders
Anxiety	0/6007 (0%)		1/6012 (0%)
Conversion Disorder	0/6007 (0%)		1/6012 (0%)
Panic Attack	1/6007 (0%)		0/6012 (0%)
Renal and urinary disorders
Acute Kidney Injury	7/6007 (0.1%)		8/6012 (0.1%)
Chronic Kidney Disease	1/6007 (0%)		2/6012 (0%)
Ketonuria	1/6007 (0%)		0/6012 (0%)
Nephritis	0/6007 (0%)		1/6012 (0%)
Nephrolithiasis	1/6007 (0%)		0/6012 (0%)
Nephrotic Syndrome	2/6007 (0%)		0/6012 (0%)
Renal Failure	3/6007 (0%)		3/6012 (0%)
Renal Impairment	1/6007 (0%)		2/6012 (0%)
Urinary Retention	3/6007 (0%)		0/6012 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema	4/6007 (0.1%)		1/6012 (0%)
Acute Respiratory Failure	7/6007 (0.1%)		9/6012 (0.1%)
Asthma	8/6007 (0.1%)		3/6012 (0%)
Bronchiectasis	1/6007 (0%)		2/6012 (0%)
Bronchitis Chronic	0/6007 (0%)		1/6012 (0%)
Bronchospasm	1/6007 (0%)		3/6012 (0%)
Chronic Obstructive Pulmonary Disease	81/6007 (1.3%)		77/6012 (1.3%)
Chronic Respiratory Failure	4/6007 (0.1%)		0/6012 (0%)
Dyspnoea	1/6007 (0%)		5/6012 (0.1%)
Hydrothorax	0/6007 (0%)		1/6012 (0%)
Interstitial Lung Disease	0/6007 (0%)		1/6012 (0%)
Lupus Pleurisy	1/6007 (0%)		0/6012 (0%)
Pickwickian Syndrome	1/6007 (0%)		0/6012 (0%)
Pleural Effusion	2/6007 (0%)		3/6012 (0%)
Pneumonia Aspiration	0/6007 (0%)		1/6012 (0%)
Pneumothorax	3/6007 (0%)		0/6012 (0%)
Pneumothorax Spontaneous	1/6007 (0%)		0/6012 (0%)
Pulmonary Arterial Hypertension	1/6007 (0%)		0/6012 (0%)
Pulmonary Congestion	1/6007 (0%)		0/6012 (0%)
Pulmonary Fibrosis	0/6007 (0%)		1/6012 (0%)
Pulmonary Mass	1/6007 (0%)		0/6012 (0%)
Pulmonary Oedema	1/6007 (0%)		4/6012 (0.1%)
Pulmonary Pneumatocele	1/6007 (0%)		0/6012 (0%)
Respiratory Distress	1/6007 (0%)		1/6012 (0%)
Respiratory Failure	9/6007 (0.1%)		8/6012 (0.1%)
Skin and subcutaneous tissue disorders
Angioedema	2/6007 (0%)		0/6012 (0%)
Dermatitis Allergic	0/6007 (0%)		1/6012 (0%)
Diabetic Foot	2/6007 (0%)		1/6012 (0%)
Rash	0/6007 (0%)		1/6012 (0%)
Skin Necrosis	0/6007 (0%)		1/6012 (0%)
Skin Ulcer	1/6007 (0%)		2/6012 (0%)
Vasculitic Ulcer	0/6007 (0%)		1/6012 (0%)
Social circumstances
Bereavement	0/6007 (0%)		1/6012 (0%)
Immobile	0/6007 (0%)		1/6012 (0%)
Surgical and medical procedures
Hospitalisation	1/6007 (0%)		0/6012 (0%)
Vascular disorders
Aortic Dissection	0/6007 (0%)		1/6012 (0%)
Aortic Stenosis	2/6007 (0%)		1/6012 (0%)
Arterial Stenosis	1/6007 (0%)		0/6012 (0%)
Distributive Shock	1/6007 (0%)		0/6012 (0%)
Hypertension	1/6007 (0%)		2/6012 (0%)
Hypertensive Crisis	0/6007 (0%)		3/6012 (0%)
Hypotension	5/6007 (0.1%)		3/6012 (0%)
Peripheral Arterial Occlusive Disease	1/6007 (0%)		0/6012 (0%)
Peripheral Artery Occlusion	1/6007 (0%)		0/6012 (0%)
Peripheral Artery Thrombosis	0/6007 (0%)		2/6012 (0%)
Peripheral Ischaemia	0/6007 (0%)		1/6012 (0%)
Post Thrombotic Syndrome	1/6007 (0%)		0/6012 (0%)
Other (Not Including Serious) Adverse Events
	Rivaroxaban 10 mg or 7.5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	250/6007 (4.2%)		280/6012 (4.7%)
Gastrointestinal disorders
Diarrhoea	69/6007 (1.1%)		52/6012 (0.9%)
Nervous system disorders
Headache	114/6007 (1.9%)		147/6012 (2.4%)
Vascular disorders
Hypertension	75/6007 (1.2%)		93/6012 (1.5%)

Limitations/Caveats

Study was stopped prior to achieving preplanned 161 participants with primary outcome events. Other limitations included how VTE-related death was defined and participants with moderate renal impairment may have been under-dosed.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.