Cancer Venous Thromboembolism (VTE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02073682

Recruitment Status : Completed

First Posted : February 27, 2014

Results First Posted : October 24, 2018

Last Update Posted : March 6, 2019

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Daiichi Sankyo

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Venous Thromboembolism (VTE) Deep Vein Thrombosis (DVT) Pulmonary Embolism (PE) Cancer
Interventions	Drug: Edoxaban Drug: Dalteparin Drug: Low molecular weight heparin
Enrollment	1046

Participant Flow

Recruitment Details	1050 participants were randomized from 114 sites in Western Europe (31), Central Europe (11), South Europe (36), Australia/New Zealand (13) and North America (23)
Pre-assignment Details	Of 1050 participants randomized, 1046 took study drug and were included in the modified Intent to Treat (mITT) and Safety Analysis Sets


Arm/Group Title	Edoxaban Group	Dalteparin Group
Arm/Group Description	After 5 days of low molecular weigh...	Participants received dalteparin da...
Arm/Group Description	After 5 days of low molecular weight heparin (LMWH), participants received edoxaban treatment daily	Participants received dalteparin daily
Period Title: Overall Study
Started	522	524
Completed ^[1]	200	154
Not Completed	322	370
Reason Not Completed
Low Creatinine Clearance	1	2
Death	86	100
Cancer Cured	10	15
ID: Patient Noncompliance	1	2
ID: Palliative Treatment Only	10	7
Prohibited Concomitant Medication Use	0	1
Platelet Count <50,000/mL	1	2
Surgery/Medical Procedure	3	1
Withdrawal by Subject	6	8
Start of New Chemotherapy Regimen	6	3
Cancer Progression	53	33
Protocol Violation	1	0
Adverse Event	79	62
No reason provided	11	9
PD: Inconvenience of Dosing	21	78
Lost to Follow-up	1	1
ID: Benefit/Risk Judgment	32	46
[1] In reasons not completed, acronyms are used: Investigator Decision (ID) and Patient Decision (PD)

Baseline Characteristics

Arm/Group Title		Edoxaban Group	Dalteparin Group	Total
Arm/Group Description		After 5 days of low molecular weigh...	Participants received dalteparin da...	Total of all reporting groups
Arm/Group Description		After 5 days of low molecular weight heparin (LMWH), participants received edoxaban treatment daily	Participants received dalteparin daily	Total of all reporting groups
Overall Number of Baseline Participants		522	524	1046
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	522 participants	524 participants	1046 participants
		66 (22 to 91)	65 (21 to 89)	65 (21 to 91)
Age, Customized Measure Type: Count of Participants Unit of measure: Participants
18-64 Years	Number Analyzed	522 participants	524 participants	1046 participants
18-64 Years		246 47.1%	261 49.8%	507 48.5%
65-84 Years	Number Analyzed	522 participants	524 participants	1046 participants
65-84 Years		267 51.1%	254 48.5%	521 49.8%
85 years and over	Number Analyzed	522 participants	524 participants	1046 participants
85 years and over		9 1.7%	9 1.7%	18 1.7%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	522 participants	524 participants	1046 participants
	Female	245 46.9%	261 49.8%	506 48.4%
	Male	277 53.1%	263 50.2%	540 51.6%
Race/Ethnicity, Customized ^[1] Measure Type: Count of Participants Unit of measure: Participants
White	Number Analyzed	509 participants	506 participants	1015 participants
White		453 89.0%	427 84.4%	880 86.7%
Black or African American	Number Analyzed	509 participants	506 participants	1015 participants
Black or African American		17 3.3%	21 4.2%	38 3.7%
Asian	Number Analyzed	509 participants	506 participants	1015 participants
Asian		6 1.2%	13 2.6%	19 1.9%
Native Hawaiian/Pacific Islander	Number Analyzed	509 participants	506 participants	1015 participants
Native Hawaiian/Pacific Islander		0 0.0%	1 0.2%	1 0.1%
Other	Number Analyzed	509 participants	506 participants	1015 participants
Other		33 6.5%	44 8.7%	77 7.6%
		[1] Measure Analysis Population Description: The number analyzed in rows differs from overall because information was not provided by some participants: 13 in the edoxaban group and 18 in the dalteparin group.
Region of Enrollment Measure Type: Number Unit of measure: Participants
Netherlands	Number Analyzed	522 participants	524 participants	1046 participants
Netherlands		61	57	118
Belgium	Number Analyzed	522 participants	524 participants	1046 participants
Belgium		22	19	41
Hungary	Number Analyzed	522 participants	524 participants	1046 participants
Hungary		17	16	33
United States	Number Analyzed	522 participants	524 participants	1046 participants
United States		104	103	207
Italy	Number Analyzed	522 participants	524 participants	1046 participants
Italy		45	45	90
France	Number Analyzed	522 participants	524 participants	1046 participants
France		58	64	122
Austria	Number Analyzed	522 participants	524 participants	1046 participants
Austria		13	15	28
Germany	Number Analyzed	522 participants	524 participants	1046 participants
Germany		30	29	59
Czechia	Number Analyzed	522 participants	524 participants	1046 participants
Czechia		11	10	21
Spain	Number Analyzed	522 participants	524 participants	1046 participants
Spain		35	35	70
Australia	Number Analyzed	522 participants	524 participants	1046 participants
Australia		16	16	32
New Zealand	Number Analyzed	522 participants	524 participants	1046 participants
New Zealand		12	13	25
Canada	Number Analyzed	522 participants	524 participants	1046 participants
Canada		98	102	200
Type of Cancer Measure Type: Count of Participants Unit of measure: Participants
Solid Tumor	Number Analyzed	522 participants	524 participants	1046 participants
Solid Tumor		465 89.1%	467 89.1%	932 89.1%
Haematological Malignancy	Number Analyzed	522 participants	524 participants	1046 participants
Haematological Malignancy		56 10.7%	55 10.5%	111 10.6%
Solid Tumor and Haematological Malignancy	Number Analyzed	522 participants	524 participants	1046 participants
Solid Tumor and Haematological Malignancy		1 0.2%	2 0.4%	3 0.3%

Outcome Measures

1.Primary Outcome


Title	Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) or Major Bleeding Event
Description	[Not Specified]
Description	[Not Specified]
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

modified Intent to Treat (mITT), equating to the Safety Analysis Set


Arm/Group Title	Edoxaban Group	Dalteparin Group
Arm/Group Description:	After 5 days of low molecular weigh...	Participants received dalteparin da...
Arm/Group Description:	After 5 days of low molecular weight heparin (LMWH), participants received edoxaban treatment daily	Participants received dalteparin daily
Overall Number of Participants Analyzed	522	524
Measure Type: Count of Participants Unit of Measure: Participants
	67 12.8%	71 13.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Edoxaban Group, Dalteparin Group
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Edoxaban Group was considered non-inferior to the Dalteparin Group if the upper limit of the 2-sided 95% confidence interval (CI) for the Hazard Ratio ([LMW] Edoxaban Group to Dalteparin Group) was less than 1.5.

Statistical Test of Hypothesis	P-Value	0.0056
	Comments	[Not Specified]
	Method	Cox proportional hazard
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95% 0.696 to 1.359
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Edoxaban Group, Dalteparin Group
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The hazard ratio (HR), two-sided confidence interval (CI) and p-value are based on the Cox proportional hazard model including treatment and the two stratification factors as covariates: the dichotomized bleeding risk and the dichotomized dose-adjustment factor.

Statistical Test of Hypothesis	P-Value	0.8712
	Comments	[Not Specified]
	Method	Cox proportional hazard
	Comments	[Not Specified]

2.Secondary Outcome


Title	Number of Participants With Adjudicated Major Bleeding Events While on Treatment
Description	The primary safety endpoint was major bleeding events during the On-Tr...
Description	The primary safety endpoint was major bleeding events during the On-Treatment Study Period (defined as on-study drug or up to 3 days after the last dose of study drug).
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Safety analysis set


Arm/Group Title	Edoxaban Group	Dalteparin Group
Arm/Group Description:	After 5 days of low molecular weigh...	Participants received dalteparin da...
Arm/Group Description:	After 5 days of low molecular weight heparin (LMWH), participants received edoxaban treatment daily	Participants received dalteparin daily
Overall Number of Participants Analyzed	522	524
Measure Type: Count of Participants Unit of Measure: Participants
	32 6.1%	16 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Edoxaban Group, Dalteparin Group
	Comments	The HR, 2-sided CI and p-value are based on the Cox regression model with counting process approach for on-treatment including treatment and the 2 stratification factors as covariates: the dichotomized bleeding risk and the dichotomized dose-adjustment factor.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0254
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95% 1.089 to 3.657
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Number of Participants With Recurrent Venous Thromboembolism (VTE) During the Overall Study Period
Description	[Not Specified]
Description	[Not Specified]
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

mITT (Safety Analysis Set)


Arm/Group Title	Edoxaban Group	Dalteparin Group
Arm/Group Description:	After 5 days of low molecular weigh...	Participants received dalteparin da...
Arm/Group Description:	After 5 days of low molecular weight heparin (LMWH), participants received edoxaban treatment daily	Participants received dalteparin daily
Overall Number of Participants Analyzed	522	524
Measure Type: Count of Participants Unit of Measure: Participants
	41 7.9%	59 11.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Edoxaban Group, Dalteparin Group
	Comments	The HR, 2-sided CI, and p-value are based on the Cox proportional hazard model including treatment and the 2 stratification factors as covariates: the dichotomized bleeding risk and the dichotomized dose-adjustment factor.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0931
	Comments	[Not Specified]
	Method	Cox proportional hazard
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95% 0.476 to 1.059
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Number of Participants With Recurrent Deep Vein Thrombosis (DVT) During the Overall Study Period
Description	[Not Specified]
Description	[Not Specified]
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

mITT (Safety Analysis Set)


Arm/Group Title	Edoxaban Group	Dalteparin Group
Arm/Group Description:	After 5 days of low molecular weigh...	Participants received dalteparin da...
Arm/Group Description:	After 5 days of low molecular weight heparin (LMWH), participants received edoxaban treatment daily	Participants received dalteparin daily
Overall Number of Participants Analyzed	522	524
Measure Type: Count of Participants Unit of Measure: Participants
	19 3.6%	35 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Edoxaban Group, Dalteparin Group
	Comments	The HR, 2-sided CI, and p-value are based on the Cox proportional hazard model including treatment and the 2 stratification factors as covariates: the dichotomized bleeding risk and the dichotomized dose-adjustment factor.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0394
	Comments	[Not Specified]
	Method	Cox proportional hazard
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95% 0.318 to 0.972
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Number of Participants With Recurrent Non-Fatal Pulmonary Embolism (PE) During the Overall Study Period
Description	[Not Specified]
Description	[Not Specified]
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

mITT (Safety Analysis Set)


Arm/Group Title	Edoxaban Group	Dalteparin Group
Arm/Group Description:	After 5 days of low molecular weigh...	Participants received dalteparin da...
Arm/Group Description:	After 5 days of low molecular weight heparin (LMWH), participants received edoxaban treatment daily	Participants received dalteparin daily
Overall Number of Participants Analyzed	522	524
Measure Type: Count of Participants Unit of Measure: Participants
	21 4.0%	24 4.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Edoxaban Group, Dalteparin Group
	Comments	The HR, 2-sided CI, and p-value are based on the Cox proportional hazard model including treatment and the 2 stratification factors as covariates: the dichotomized bleeding risk and the dichotomized dose-adjustment factor.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.7324
	Comments	[Not Specified]
	Method	Cox proportional hazard
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95% 0.502 to 1.624
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Number of Participants With VTE-Related Death
Description	[Not Specified]
Description	[Not Specified]
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

mITT (Safety Analysis Set)


Arm/Group Title	Edoxaban Group	Dalteparin Group
Arm/Group Description:	After 5 days of low molecular weigh...	Participants received dalteparin da...
Arm/Group Description:	After 5 days of low molecular weight heparin (LMWH), participants received edoxaban treatment daily	Participants received dalteparin daily
Overall Number of Participants Analyzed	522	524
Measure Type: Count of Participants Unit of Measure: Participants
	6 1.1%	4 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Edoxaban Group, Dalteparin Group
	Comments	The HR, 2-sided CI, and p-value are based on the Cox proportional hazard model including treatment and the 2 stratification factors as covariates: the dichotomized bleeding risk and the dichotomized dose-adjustment factor.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4873
	Comments	[Not Specified]
	Method	Cox proportional hazard
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.56
	Confidence Interval	(2-Sided) 95% 0.444 to 5.505
	Estimation Comments	[Not Specified]

7.Secondary Outcome


Title	Number of Participants With Recurrent VTE, Major Bleed or All-Cause Death
Description	[Not Specified]
Description	[Not Specified]
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

mITT (Safety Analysis Set)


Arm/Group Title	Edoxaban Group	Dalteparin Group
Arm/Group Description:	After 5 days of low molecular weigh...	Participants received dalteparin da...
Arm/Group Description:	After 5 days of low molecular weight heparin (LMWH), participants received edoxaban treatment daily	Participants received dalteparin daily
Overall Number of Participants Analyzed	522	524
Measure Type: Count of Participants Unit of Measure: Participants
	235 45.0%	228 43.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Edoxaban Group, Dalteparin Group
	Comments	The HR, 2-sided CI, and p-value are based on the Cox proportional hazard model including treatment and the 2 stratification factors as covariates: the dichotomized bleeding risk and the dichotomized dose-adjustment factor.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4199
	Comments	[Not Specified]
	Method	Cox proportional hazard
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95% 0.898 to 1.293
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Edoxaban Group		Dalteparin Group
Arm/Group Description	After 5 days of low molecular weigh...		Participants received dalteparin da...
Arm/Group Description	After 5 days of low molecular weight heparin (LMWH), participants received edoxaban treatment daily		Participants received dalteparin daily
All-Cause Mortality
	Edoxaban Group		Dalteparin Group
	Affected / at Risk (%)		Affected / at Risk (%)
Total	206/522 (39.46%)		192/524 (36.64%)
Serious Adverse Events Serious Adverse Events
	Edoxaban Group		Dalteparin Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	276/522 (52.87%)		251/524 (47.90%)
Blood and lymphatic system disorders
Anaemia ^† 1	4/522 (0.77%)	4	2/524 (0.38%)	2
Disseminated intravascular coagulation ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Heparin-induced thrombocytopenia ^† 1	0/522 (0.00%)	0	4/524 (0.76%)	4
Immune thrombocytopenic purpura ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Cardiac disorders
Acute coronary syndrome ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Acute myocardial infarction ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Angina pectoris ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Atrial fibrillation ^† 1	3/522 (0.57%)	3	0/524 (0.00%)	0
Atrial flutter ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Cardiac arrest ^† 1	1/522 (0.19%)	1	3/524 (0.57%)	3
Cardiac failure ^† 1	2/522 (0.38%)	2	0/524 (0.00%)	0
Cardiac failure congestive ^† 1	2/522 (0.38%)	2	0/524 (0.00%)	0
Cardiac tamponade ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Cardiopulmonary failure ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Cardiovascular disorder ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Intracardiac mass ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Ischaemic cardiomyopathy ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Myocardial infarction ^† 1	1/522 (0.19%)	1	3/524 (0.57%)	3
Pulseless electrical activity ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Tachycardia ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Congenital, familial and genetic disorders
Atrial septal defect ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Gastrointestinal disorders
Abdominal incarcerated hernia ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Abdominal wall haematoma ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Colonic fistula ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Diarrhoea ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Dysphagia ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Faecaloma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Gastric ulcer ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Gastrointestinal haemorrhage ^† 1	11/522 (2.11%)	12	3/524 (0.57%)	3
Haematemesis ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Haematochezia ^† 1	0/522 (0.00%)	0	2/524 (0.38%)	2
Haemorrhoidal haemorrhage ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Ileal stenosis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Ileus ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Intestinal obstruction ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Intra-abdominal haemorrhage ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Lower gastrointestinal haemorrhage ^† 1	2/522 (0.38%)	2	1/524 (0.19%)	1
Melaena ^† 1	4/522 (0.77%)	4	0/524 (0.00%)	0
Peptic ulcer ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Peritoneal haemorrhage ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Rectal haemorrhage ^† 1	5/522 (0.96%)	5	0/524 (0.00%)	0
Retroperitoneal haematoma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Retroperitoneal haemorrhage ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Small intestinal obstruction ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Upper gastrointestinal haemorrhage ^† 1	4/522 (0.77%)	6	0/524 (0.00%)	0
Vomiting ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
General disorders
Adverse drug reaction ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Asthenia ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Catheter site haemorrhage ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Chest pain ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	2
Death ^† 1	4/522 (0.77%)	4	4/524 (0.76%)	4
Disease progression ^† 1	4/522 (0.77%)	4	2/524 (0.38%)	2
Euthanasia ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Fatigue ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
General physical health deterioration ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Malaise ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Multi-organ failure ^† 1	2/522 (0.38%)	2	3/524 (0.57%)	3
Oedema peripheral ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Peripheral swelling ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Pyrexia ^† 1	3/522 (0.57%)	3	0/524 (0.00%)	0
Sudden death ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Systemic inflammatory response syndrome ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Hepatobiliary disorders
Acute hepatic failure ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Bile duct stenosis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Cholangitis ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Cholecystitis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Hepatic function abnormal ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Portal vein thrombosis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Infections and infestations
Abscess limb ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Appendicitis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Bronchitis ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Campylobacter gastroenteritis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Cellulitis ^† 1	2/522 (0.38%)	4	2/524 (0.38%)	2
Erysipelas ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Gastroenteritis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Infection ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Infectious pleural effusion ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Influenza ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Lower respiratory tract infection ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Lower respiratory tract infection bacterial ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Lung infection ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Meningococcal sepsis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Pneumonia ^† 1	16/522 (3.07%)	17	13/524 (2.48%)	13
Pneumonia bacterial ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Pneumonia viral ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Post procedural sepsis ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Postoperative abscess ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Pyelonephritis ^† 1	0/522 (0.00%)	0	3/524 (0.57%)	3
Respiratory syncytial virus infection ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Sepsis ^† 1	4/522 (0.77%)	4	7/524 (1.34%)	7
Septic shock ^† 1	3/522 (0.57%)	3	1/524 (0.19%)	1
Staphylococcal sepsis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Subcutaneous abscess ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Subdiaphragmatic abscess ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Urinary tract infection ^† 1	1/522 (0.19%)	1	4/524 (0.76%)	4
Urosepsis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Injury, poisoning and procedural complications
Ankle fracture ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Fall ^† 1	0/522 (0.00%)	0	3/524 (0.57%)	3
Femur fracture ^† 1	2/522 (0.38%)	2	1/524 (0.19%)	1
Foot fracture ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Head injury ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Post procedural haematoma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Post procedural haematuria ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Stoma site haemorrhage ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Urinary tract stoma complication ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Vascular procedure complication ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Wound haemorrhage ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Investigations
Creatinine renal clearance decreased ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Hepatic enzyme increased ^† 1	0/522 (0.00%)	0	3/524 (0.57%)	3
Transaminases increased ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Metabolism and nutrition disorders
Cachexia ^† 1	4/522 (0.77%)	4	2/524 (0.38%)	2
Dehydration ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Diabetic ketoacidosis ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Hyponatraemia ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Musculoskeletal and connective tissue disorders
Muscle haemorrhage ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Pain in extremity ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Pathological fracture ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma ^† 1	2/522 (0.38%)	2	3/524 (0.57%)	3
Adenocarcinoma gastric ^† 1	2/522 (0.38%)	2	1/524 (0.19%)	1
Adenocarcinoma of colon ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Adenocarcinoma pancreas ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
B-cell lymphoma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Bladder cancer ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Brain cancer metastatic ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Breast cancer ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Breast cancer metastatic ^† 1	0/522 (0.00%)	0	4/524 (0.76%)	4
Cervix cancer metastatic ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Cholangiocarcinoma ^† 1	2/522 (0.38%)	2	0/524 (0.00%)	0
Colon cancer ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Colon cancer metastatic ^† 1	2/522 (0.38%)	2	1/524 (0.19%)	1
Colorectal cancer ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Colorectal cancer metastatic ^† 1	2/522 (0.38%)	2	1/524 (0.19%)	1
Endometrial adenocarcinoma ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Endometrial cancer ^† 1	2/522 (0.38%)	2	2/524 (0.38%)	2
Endometrial cancer metastatic ^† 1	1/522 (0.19%)	1	3/524 (0.57%)	3
Gallbladder cancer ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Gastric cancer ^† 1	2/522 (0.38%)	2	0/524 (0.00%)	0
Glioblastoma ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Huerthle cell carcinoma ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Liposarcoma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Lung adenocarcinoma ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Lung adenocarcinoma metastatic ^† 1	3/522 (0.57%)	3	2/524 (0.38%)	2
Lung cancer metastatic ^† 1	3/522 (0.57%)	3	4/524 (0.76%)	4
Lung neoplasm malignant ^† 1	8/522 (1.53%)	8	6/524 (1.15%)	6
Malignant neoplasm of unknown primary site ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
Malignant anorectal neoplasm ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Malignant neoplasm progression ^† 1	69/522 (13.22%)	69	67/524 (12.79%)	67
Metastases to central nervous system ^† 1	3/522 (0.57%)	3	2/524 (0.38%)	2
Metastases to liver ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Metastases to lung ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Metastases to lymph nodes ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Metastases to rectum ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Metastatic carcinoma of the bladder ^† 1	2/522 (0.38%)	2	0/524 (0.00%)	0
Metastatic neoplasm ^† 1	1/522 (0.19%)	1	2/524 (0.38%)	2
Myelodysplastic syndrome ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Neoplasm malignant ^† 1	1/522 (0.19%)	1	2/524 (0.38%)	2
Neoplasm progression ^† 1	24/522 (4.60%)	24	21/524 (4.01%)	21
Non-small cell lung cancer ^† 1	2/522 (0.38%)	2	2/524 (0.38%)	2
Non-small cell lung cancer metastatic ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Ovarian cancer ^† 1	0/522 (0.00%)	0	3/524 (0.57%)	3
Ovarian cancer metastatic ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Pancreatic carcinoma ^† 1	4/522 (0.77%)	4	0/524 (0.00%)	0
Pancreatic carcinoma metastatic ^† 1	2/522 (0.38%)	2	3/524 (0.57%)	3
Plasma cell myeloma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Prostate cancer ^† 1	0/522 (0.00%)	0	3/524 (0.57%)	3
Prostate cancer metastatic ^† 1	3/522 (0.57%)	3	0/524 (0.00%)	0
Rectal adenocarcinoma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Rectal cancer metastatic ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Renal cancer ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Renal cancer metastatic ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Renal cell carcinoma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Sarcoma ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Small cell carcinoma ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Squamous cell carcinoma ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Transitional cell carcinoma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Tumour haemorrhage ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Uterine cancer ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Vulvar cancer ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Nervous system disorders
Altered state of consciousness ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Basal ganglia haemorrhage ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Central nervous system haemorrhage ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Cerebral haematoma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Cerebral haemorrhage ^† 1	2/522 (0.38%)	2	1/524 (0.19%)	1
Cerebral infarction ^† 1	2/522 (0.38%)	2	0/524 (0.00%)	0
Cerebrovascular accident ^† 1	3/522 (0.57%)	3	4/524 (0.76%)	4
Encephalopathy ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Haemorrhage intracranial ^† 1	2/522 (0.38%)	2	3/524 (0.57%)	3
Haemorrhagic stroke ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Intracranial haematoma ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Ischaemic stroke ^† 1	6/522 (1.15%)	6	4/524 (0.76%)	4
Leukoencephalopathy ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Loss of consciousness ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Seizure ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Spinal cord haemorrhage ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Subarachnoid haemorrhage ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	2
Syncope ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Thrombotic stroke ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Transient ischaemic attack ^† 1	2/522 (0.38%)	3	1/524 (0.19%)	1
VIIth nerve paralysis ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Unintended pregnancy ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Psychiatric disorders
Confusional state ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Depression ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Renal and urinary disorders
Acute kidney injury ^† 1	0/522 (0.00%)	0	2/524 (0.38%)	2
Calculus bladder ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Calculus ureteric ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Haematuria ^† 1	5/522 (0.96%)	6	4/524 (0.76%)	4
Hydronephrosis ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Renal failure ^† 1	2/522 (0.38%)	2	0/524 (0.00%)	0
Renal infarct ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Genital haemorrhage ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Vaginal haemorrhage ^† 1	2/522 (0.38%)	2	0/524 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Acute respiratory failure ^† 1	1/522 (0.19%)	1	2/524 (0.38%)	2
Asthma ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Chronic obstructive pulmonary disease ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	3
Dyspnoea ^† 1	3/522 (0.57%)	3	2/524 (0.38%)	2
Epistaxis ^† 1	5/522 (0.96%)	6	1/524 (0.19%)	1
Haemoptysis ^† 1	1/522 (0.19%)	1	3/524 (0.57%)	4
Haemothorax ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Hyperventilation ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Hypoxia ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Interstitial lung disease ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Laryngeal haemorrhage ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Lung disorder ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Lung infiltration ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Pleural effusion ^† 1	2/522 (0.38%)	2	1/524 (0.19%)	1
Pneumonitis ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Pneumothorax ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Pulmonary embolism ^† 1	8/522 (1.53%)	9	16/524 (3.05%)	17
Pulmonary oedema ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Respiratory arrest ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Respiratory failure ^† 1	7/522 (1.34%)	7	6/524 (1.15%)	6
Skin and subcutaneous tissue disorders
Drug eruption ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Rash ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Stevens-Johnson syndrome ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Vascular disorders
Aortic aneurysm ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Arterial haemorrhage ^† 1	0/522 (0.00%)	0	1/524 (0.19%)	1
Deep vein thrombosis ^† 1	13/522 (2.49%)	13	8/524 (1.53%)	8
Embolism arterial ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Femoral artery embolism ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Haematoma ^† 1	1/522 (0.19%)	1	2/524 (0.38%)	2
Hypertension ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Peripheral ischaemia ^† 1	1/522 (0.19%)	2	0/524 (0.00%)	0
Thrombophlebitis superficial ^† 1	1/522 (0.19%)	1	0/524 (0.00%)	0
Venous thrombosis ^† 1	1/522 (0.19%)	1	1/524 (0.19%)	1
1 Term from vocabulary, MedDRA (18.0) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Edoxaban Group		Dalteparin Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/522 (14.37%)		67/524 (12.79%)
Respiratory, thoracic and mediastinal disorders
Epistaxis ^† 1	41/522 (7.85%)	44	30/524 (5.73%)	42
Vascular disorders
Deep vein thrombosis ^† 1	34/522 (6.51%)	40	37/524 (7.06%)	45
1 Term from vocabulary, MedDRA (18.0) † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Daiichi Sankyo US Contact for Clinical Trial Results
Organization:	Daiichi Sankyo, Inc.
Phone:	1-908-992-6400
EMail:	CTRinfo@DSI.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Buller HR; Hokusai VTE Cancer Investigators. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. doi: 10.1056/NEJMoa1711948. Epub 2017 Dec 12.

van Es N, Di Nisio M, Bleker SM, Segers A, Mercuri MF, Schwocho L, Kakkar A, Weitz JI, Beyer-Westendorf J, Boda Z, Carrier M, Chlumsky J, Decousus H, Garcia D, Gibbs H, Kamphuisen PW, Monreal M, Ockelford P, Pabinger I, Verhamme P, Grosso MA, Buller HR, Raskob GE. Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study. Thromb Haemost. 2015 Nov 25;114(6):1268-76. doi: 10.1160/TH15-06-0452. Epub 2015 Aug 13.

Layout table for additonal information

Responsible Party:	Daiichi Sankyo
ClinicalTrials.gov Identifier:	NCT02073682
Other Study ID Numbers:	DU176b-D-U311 2014-004708-30 ( EudraCT Number )
First Submitted:	February 25, 2014
First Posted:	February 27, 2014
Results First Submitted:	September 26, 2018
Results First Posted:	October 24, 2018
Last Update Posted:	March 6, 2019

To Top