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Edoxaban vs. Warfarin in Subjects Undergoing Cardioversion of Nonvalvular Atrial Fibrillation (NVAF) (ENSURE-AF)

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: NCT02072434
Recruitment Status : Completed
First Posted : February 26, 2014
Results First Posted : March 13, 2019
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Atrial Fibrillation
Interventions Drug: Edoxaban
Drug: Warfarin
Drug: Enoxaparin
Enrollment 2199
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Edoxaban Warfarin
Hide Arm/Group Description Participants randomized to receive Edoxaban Participants randomized to receive Warfarin
Period Title: Overall Study
Started 1095 1104
Intent to Treat Analysis Set 1095 1104
Received Study Drug 1067 1082
Safety Analysis Set 1067 1082
Completed 1041 1014
Not Completed 54 90
Reason Not Completed
Protocol Violation             10             9
Physician Decision             5             10
Adverse event, serious fatal             1             6
Adverse Event             7             6
Withdrawal by Subject             17             29
Not specified             14             29
Lost to Follow-up             0             1
Arm/Group Title Edoxaban Warfarin Total
Hide Arm/Group Description Participants randomized to receive Edoxaban Participants randomized to receive Warfarin Total of all reporting groups
Overall Number of Baseline Participants 1095 1104 2199
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1095 participants 1104 participants 2199 participants
64.3  (10.34) 64.2  (10.75) 64.2  (10.54)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Age, Categorical Number Analyzed 1095 participants 1104 participants 2199 participants
<75 years
923
  84.3%
917
  83.1%
1840
  83.7%
≥75 years
172
  15.7%
187
  16.9%
359
  16.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1095 participants 1104 participants 2199 participants
Female
374
  34.2%
382
  34.6%
756
  34.4%
Male
721
  65.8%
722
  65.4%
1443
  65.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1095 participants 1104 participants 2199 participants
Romania 68 54 122
Hungary 89 90 179
United States 46 49 95
Czechia 86 87 173
Ukraine 206 224 430
United Kingdom 76 83 159
Russia 110 106 216
Spain 73 69 142
Austria 19 13 32
Netherlands 24 23 47
Sweden 7 7 14
Belgium 19 22 41
Denmark 26 31 57
Poland 21 33 54
Italy 34 35 69
Israel 39 43 82
Bulgaria 70 55 125
France 26 13 39
Germany 56 67 123
1.Primary Outcome
Title Percentage of Participants With Composite Endpoint of Stroke, Systemic Embolic Stroke (SEE), Myocardial Infarction (MI) and Cardiovascular (CV) Mortality From Randomization to End of Follow up
Hide Description [Not Specified]
Time Frame Randomization to end of follow-up (within 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome was assessed in the Intent-to-Treat (ITT) Analysis Set.
Arm/Group Title Edoxaban Warfarin
Hide Arm/Group Description:
Participants randomized to receive Edoxaban
Participants randomized to receive Warfarin
Overall Number of Participants Analyzed 1095 1104
Measure Type: Number
Unit of Measure: Percentage of participants
0.5 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Edoxaban, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.12 to 1.43
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Composite Endpoints of Major and Clinically-relevant Non-major (CRNM) Bleeding
Hide Description [Not Specified]
Time Frame During treatment period (within 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome was assessed in the Safety Analysis Set.
Arm/Group Title Edoxaban Warfarin
Hide Arm/Group Description:
Participants randomized to receive Edoxaban
Participants randomized to receive Warfarin
Overall Number of Participants Analyzed 1067 1082
Measure Type: Number
Unit of Measure: Percentage of participants
1.5 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Edoxaban, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.48
Confidence Interval (2-Sided) 95%
0.64 to 3.55
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Composite Endpoints of Stroke, SEE, MI, CV Mortality, and Major Bleeding
Hide Description [Not Specified]
Time Frame From randomization to the end of follow-up (within 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome was assessed in the ITT Analysis Set.
Arm/Group Title Edoxaban Warfarin
Hide Arm/Group Description:
Participants randomized to receive Edoxaban
Participants randomized to receive Warfarin
Overall Number of Participants Analyzed 1095 1104
Measure Type: Number
Unit of Measure: Percentage of participants
0.7 1.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Edoxaban, Warfarin
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between percentages
Estimated Value -0.72
Confidence Interval (2-Sided) 95%
-1.59 to 0.15
Estimation Comments [Not Specified]
Time Frame Treatment-emergent adverse events (TEAEs) were defined as events that started on or after the first dose of study drug or started prior to but then became worse after the first dose of study drug through 30 days after the last dose of study drug (within 2 years).
Adverse Event Reporting Description This table includes counts of participants in the Safety Analysis Set. Participants who experienced more than one episode of an adverse event are counted only once within a preferred term. Participants who experienced more than one adverse event within a system organ class are counted once for each preferred term, but only once for the system organ class.
 
Arm/Group Title Edoxaban Warfarin
Hide Arm/Group Description Participants randomized to receive Edoxaban Participants randomized to receive Warfarin
All-Cause Mortality
Edoxaban Warfarin
Affected / at Risk (%) Affected / at Risk (%)
Total   1/1067 (0.09%)      5/1082 (0.46%)    
Show Serious Adverse Events Hide Serious Adverse Events
Edoxaban Warfarin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   85/1067 (7.97%)      83/1082 (7.67%)    
Blood and lymphatic system disorders     
Anaemia  1  2/1067 (0.19%)  2 0/1082 (0.00%)  0
Hypocoagulable state  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Iron deficiency anaemia  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Leukocytosis  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Cardiac disorders     
Atrial fibrillation  1  20/1067 (1.87%)  20 14/1082 (1.29%)  14
Cardiac failure  1 [1]  3/1067 (0.28%)  3 6/1082 (0.55%)  6
Cardiac failure congestive  1 [2]  5/1067 (0.47%)  5 3/1082 (0.28%)  3
Atrial flutter  1  3/1067 (0.28%)  3 2/1082 (0.18%)  2
Sick sinus syndrome  1  2/1067 (0.19%)  2 2/1082 (0.18%)  2
Acute myocardial infarction  1  1/1067 (0.09%)  1 2/1082 (0.18%)  2
Bradycardia  1  2/1067 (0.19%)  2 1/1082 (0.09%)  1
Cardiac failure acute  1  3/1067 (0.28%)  3 0/1082 (0.00%)  0
Mitral valve incompetence  1  2/1067 (0.19%)  2 1/1082 (0.09%)  1
Myocardial infarction  1  1/1067 (0.09%)  1 2/1082 (0.18%)  2
Palpitations  1  2/1067 (0.19%)  2 1/1082 (0.09%)  1
Angina unstable  1  0/1067 (0.00%)  0 2/1082 (0.18%)  2
Atrioventricular block complete  1  2/1067 (0.19%)  2 0/1082 (0.00%)  0
Cardiac arrest  1 [3]  0/1067 (0.00%)  0 2/1082 (0.18%)  2
Angina pectoris  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Arrhythmia  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Atrioventricular block second degree  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Cardio-respiratory arrest  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Chordae tendinae rupture  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Coronary artery stenosis  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Left ventricular failure  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Tachycardia  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Torsade de pointes  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Ventricular tachycardia  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Sinus bradycardia  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Ear and labyrinth disorders     
Vertigo positional  1  0/1067 (0.00%)  0 2/1082 (0.18%)  2
Endocrine disorders     
Hyperadrenocorticism  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Gastrointestinal disorders     
Diarrhea  1  2/1067 (0.19%)  2 0/1082 (0.00%)  0
Haematochezia  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Haemorrhoidal haemorrhage  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Lower gastrointestinal haemorrhage  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Pancreatitis  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Retroperitoneal haematoma  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Retroperitoneal haemorrhage  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Spigelian hernia  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
General disorders     
Asthenia  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Death  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Drug effect increased  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Injection site bruising  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Infections and infestations     
Pneumonia  1  4/1067 (0.37%)  4 4/1082 (0.37%)  4
Erysipelas  1  1/1067 (0.09%)  1 1/1082 (0.09%)  1
Lower respiratory tract infection  1  1/1067 (0.09%)  1 1/1082 (0.09%)  1
Arthritis bacterial  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Cellulitis  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Chronic sinusitis  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Clostridium difficile infection  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Endocarditis bacterial  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Gastroenteritis  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Infective aneurysm  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Liver abscess  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Lung infection  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Pneumonia haemophilus  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Sepsis  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Urosepsis  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Injury, poisoning and procedural complications     
Alcohol poisoning  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Ankle fracture  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Concussion  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Post procedural haemorrhage  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Traumatic haemorrhage  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Investigations     
International normalised ratio increased  1  4/1067 (0.37%)  4 10/1082 (0.92%)  10
Liver function test abnormal  1  2/1067 (0.19%)  2 1/1082 (0.09%)  1
Blood urine present  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Coagulation test abnormal  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
International normalised ratio fluctuation  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Oxygen saturation decreased  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Hypokalaemia  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Hyponatraemia  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Musculoskeletal and connective tissue disorders     
Haemarthrosis  1  0/1067 (0.00%)  0 2/1082 (0.18%)  2
Back pain  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Osteoarthritis  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Rhabdomyolysis  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Non-small cell lung cancer  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Oesophageal carcinoma  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Nervous system disorders     
Cerebrovascular accident  1  1/1067 (0.09%)  1 2/1082 (0.18%)  2
Syncope  1  2/1067 (0.19%)  2 0/1082 (0.00%)  0
Transient ischaemic attack  1  1/1067 (0.09%)  1 1/1082 (0.09%)  1
Headache  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Loss of consciousness  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Presyncope  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Renal and urinary disorders     
Renal failure acute  1  3/1067 (0.28%)  3 2/1082 (0.18%)  2
Haematuria  1  1/1067 (0.09%)  1 1/1082 (0.09%)  1
Cystitis haemorrhagic  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary oedema  1  2/1067 (0.19%)  2 1/1082 (0.09%)  1
Chronic obstructive pulmonary disease  1  1/1067 (0.09%)  1 1/1082 (0.09%)  1
Epistaxis  1  2/1067 (0.19%)  2 0/1082 (0.00%)  0
Acute pulmonary oedema  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Acute respiratory distress syndrome  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Bronchiectasis  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Mediastinal cyst  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Pulomonary haemorrhage  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Respiratory failure  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Skin and subcutaneous tissue disorders     
Eczema  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Vascular disorders     
Hypertensive crisis  1  1/1067 (0.09%)  1 1/1082 (0.09%)  1
Aortic aneurysm rupture  1 [4]  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Deep vein thrombosis  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Haemodynamic instability  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Peripheral artery thrombosis  1  0/1067 (0.00%)  0 1/1082 (0.09%)  1
Peripheral embolism  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
Thrombophlebitis  1  1/1067 (0.09%)  1 0/1082 (0.00%)  0
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
[1]
Decompensated heart failure
[2]
Acute, congestive heart failure
[3]
Cardiac arrest, ventricular fibrillation
[4]
Aneurysm with rupture abdominal aorta
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Edoxaban Warfarin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   53/1067 (4.97%)      53/1082 (4.90%)    
Cardiac disorders     
Atrial fibrillation  1  53/1067 (4.97%)  53 53/1082 (4.90%)  53
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
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
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02072434     History of Changes
Other Study ID Numbers: DU176b-F-E308
2013-003148-21 ( EudraCT Number )
First Submitted: February 20, 2014
First Posted: February 26, 2014
Results First Submitted: January 30, 2019
Results First Posted: March 13, 2019
Last Update Posted: March 15, 2019