Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Pulmonary Embolism - The EINSTEIN PE Study

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00439777
First received: February 23, 2007
Last updated: January 25, 2014
Last verified: January 2014
Results First Received: November 22, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Pulmonary Embolism
Interventions: Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Enoxaparin overlapping with and followed by VKA

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants with confirmed acute symptomatic pulmonary embolism (PE) with or without symptomatic deep vein thrombosis (DVT) were recruited at specialized study sites.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Out of 4843 participants screened, 10 failed screening (6 due to protocol violations, 2 due to investigator decision and another 2 subjects due to technical problems [interactive voice response system did not work properly]). 4833 participants were randomized (2420 to rivaroxaban and 2413 to enoxaparin/VKA).

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Enoxaparin/VKA Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)

Participant Flow for 2 periods

Period 1:   Treatment Period
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin/VKA  
STARTED     2420     2413  
Participants Received Treatment     2412     2405  
COMPLETED     2001     1954  
NOT COMPLETED     419     459  
Death                 29                 21  
Study terminated by sponsor                 125                 132  
Site closed by investigator                 0                 1  
Did not take study treatment                 7                 8  
Adverse Event                 111                 92  
Protocol Violation                 23                 30  
Withdrawal by Subject                 66                 118  
Lack of Efficacy                 1                 4  
Lost to Follow-up                 8                 10  
Protocol driven decision point                 1                 3  
Physician Decision                 7                 18  
Clinical endpoint reached                 26                 13  
Technical problems                 3                 1  
Participant convenience                 12                 8  

Period 2:   Observational Period
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin/VKA  
STARTED     2206 [1]   2197 [1]
COMPLETED     2165     2156  
NOT COMPLETED     41     41  
Protocol Violation                 0                 2  
Withdrawal by Subject                 9                 5  
Lost to Follow-up                 1                 11  
Death                 27                 20  
Study terminated by sponsor                 3                 1  
Protocol driven decision point                 0                 1  
Lack of Efficacy                 1                 0  
Technical problems                 0                 1  
[1] All participants who took any study medication and entered the observational period.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Enoxaparin/VKA Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
Total Total of all reporting groups

Baseline Measures
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin/VKA     Total  
Number of Participants  
[units: participants]
  2419     2413     4832  
Age [1]
[units: Years]
Mean ± Standard Deviation
  57.9  ± 17.3     57.5  ± 17.2     57.7  ± 17.3  
Age, Customized [1]
[units: Participants]
     
18 - < 40 years     410     432     842  
40 - < 60 years     794     779     1573  
60 - < 75 years     740     754     1494  
≥ 75 years     475     448     923  
Gender [1]
[units: Participants]
     
Female     1309     1247     2556  
Male     1110     1166     2276  
[1] Intention-to-treat (ITT) population



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) Until the Intended End of Study Treatment   [ Time Frame: 3-, 6-, or 12-month study treatment period ]

2.  Secondary:   Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment   [ Time Frame: 3-, 6-, or 12-month study treatment period ]

3.  Secondary:   Percentage of Participants With an Event for Net Clinical Benefit 1 Until the Intended End of Study Treatment   [ Time Frame: 3-, 6-, or 12-month study treatment period ]

4.  Secondary:   Percentage of Participants With Recurrent PE Until the Intended End of Study Treatment   [ Time Frame: 3-, 6- or 12-month study treatment period ]

5.  Secondary:   Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment   [ Time Frame: 3-, 6- or 12-month study treatment period ]

6.  Secondary:   Percentage of Participants With Clinically Relevant Bleeding, Treatment-emergent (Time Window: Until 2 Days After Last Dose)   [ Time Frame: 3-, 6- or 12-month study treatment period ]

7.  Secondary:   Percentage of Participants With All Deaths   [ Time Frame: 3-, 6- or 12-month study treatment period ]

8.  Secondary:   Percentage of Participants With Other Vascular Events, On-treatment (Time Window: Until 1 Day After Last Dose)   [ Time Frame: 3-, 6- or 12-month study treatment period ]

9.  Other Pre-specified:   Percentage of Participants With the Individual Components of Efficacy Outcomes Until the Intended End of Study Treatment   [ Time Frame: 3-, 6- or 12-month study treatment period ]

10.  Other Pre-specified:   Percentage of Participants With Symptomatic Recurrent VTE (i.e. the Composite of Recurrent DVT or Fatal or Non-fatal PE) During Observational Period   [ Time Frame: Up to 30 days after the last intake of study medication ]

11.  Other Pre-specified:   Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period   [ Time Frame: Up to 30 days after the last intake of study medication ]

12.  Other Pre-specified:   Percentage of Participants With an Event for Net Clinical Benefit 1 During Observational Period   [ Time Frame: Up to 30 days after the last intake of study medication ]

13.  Other Pre-specified:   Percentage of Participants With Recurrent DVT During Observational Period   [ Time Frame: Up to 30 days after the last intake of study medication ]

14.  Other Pre-specified:   Percentage of Participants With the Individual Components of Efficacy Outcomes During Observational Period   [ Time Frame: Up to 30 days after the last intake of study medication ]

15.  Post-Hoc:   Percentage of Participants With an Event for Net Clinical Benefit 2 Until the Intended End of Study Treatment   [ Time Frame: 3-, 6- or 12-month study treatment period ]

16.  Post-Hoc:   Percentage of Participants With an Event for Net Clinical Benefit 2 During Observational Period   [ Time Frame: Up to 30 days after the last intake of study medication ]


  Serious Adverse Events
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Additional Description No text entered.

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.)
Enoxaparin/VKA Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)

Serious Adverse Events
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin/VKA  
Total, serious adverse events      
# participants affected / at risk     504/2412 (20.90%)     495/2405 (20.58%)  
Blood and lymphatic system disorders      
Anaemia * 1    
# participants affected / at risk     14/2412 (0.58%)     6/2405 (0.25%)  
Anaemia folate deficiency * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Coagulopathy * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Disseminated intravascular coagulation * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Eosinophilia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Febrile neutropenia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Haemolytic anaemia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Hypercoagulation * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Idiopathic thrombocytopenic purpura * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Leukopenia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Lymphadenopathy * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Neutropenia * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Pancytopenia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pernicious anaemia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Splenic haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Splenic infarction * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Thrombocytopenia * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Haemorrhagic anaemia * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Cardiac disorders      
Acute myocardial infarction * 1    
# participants affected / at risk     6/2412 (0.25%)     10/2405 (0.42%)  
Angina pectoris * 1    
# participants affected / at risk     3/2412 (0.12%)     4/2405 (0.17%)  
Angina unstable * 1    
# participants affected / at risk     7/2412 (0.29%)     2/2405 (0.08%)  
Arrhythmia * 1    
# participants affected / at risk     2/2412 (0.08%)     1/2405 (0.04%)  
Atrial fibrillation * 1    
# participants affected / at risk     8/2412 (0.33%)     11/2405 (0.46%)  
Atrial flutter * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Atrioventricular block * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Cardiac arrest * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cardiac failure * 1    
# participants affected / at risk     9/2412 (0.37%)     7/2405 (0.29%)  
Cardiac failure acute * 1    
# participants affected / at risk     4/2412 (0.17%)     2/2405 (0.08%)  
Cardiac failure congestive * 1    
# participants affected / at risk     4/2412 (0.17%)     5/2405 (0.21%)  
Cardio-respiratory arrest * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cardiogenic shock * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cardiomyopathy * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Cor pulmonale * 1    
# participants affected / at risk     3/2412 (0.12%)     1/2405 (0.04%)  
Cor pulmonale acute * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cor pulmonale chronic * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Coronary artery disease * 1    
# participants affected / at risk     1/2412 (0.04%)     8/2405 (0.33%)  
Coronary artery stenosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Left ventricular failure * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Mitral valve incompetence * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Myocardial infarction * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Myocardial ischaemia * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Myocarditis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Palpitations * 1    
# participants affected / at risk     2/2412 (0.08%)     2/2405 (0.08%)  
Pericardial effusion * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Pericardial haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Pericarditis * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Right ventricular failure * 1    
# participants affected / at risk     3/2412 (0.12%)     0/2405 (0.00%)  
Sick sinus syndrome * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Sinus tachycardia * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Supraventricular tachycardia * 1    
# participants affected / at risk     1/2412 (0.04%)     4/2405 (0.17%)  
Tachycardia * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Ventricular fibrillation * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Ventricular tachycardia * 1    
# participants affected / at risk     3/2412 (0.12%)     1/2405 (0.04%)  
Coronary artery dissection * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Acute coronary syndrome * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Congestive cardiomyopathy * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Acute left ventricular failure * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Congenital, familial and genetic disorders      
Atrial septal defect * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Hydrocele * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Phimosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Ear and labyrinth disorders      
Vertigo * 1    
# participants affected / at risk     3/2412 (0.12%)     4/2405 (0.17%)  
Vertigo positional * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Deafness unilateral * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Sudden hearing loss * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Endocrine disorders      
Addison's disease * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Adrenal haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Diabetes insipidus * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Goitre * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Hyperparathyroidism primary * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hyperthyroidism * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Eye disorders      
Amaurosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Cataract * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Diplopia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Eye haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     3/2405 (0.12%)  
Eye pain * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Optic ischaemic neuropathy * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Retinal degeneration * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Retinal haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Vision blurred * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Age-related macular degeneration * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Gastrointestinal disorders      
Abdominal pain * 1    
# participants affected / at risk     1/2412 (0.04%)     4/2405 (0.17%)  
Abdominal pain upper * 1    
# participants affected / at risk     1/2412 (0.04%)     4/2405 (0.17%)  
Acute abdomen * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Anorectal disorder * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Ascites * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Colitis * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Colitis ischaemic * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Colonic polyp * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Colonic stenosis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Dental caries * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Diarrhoea * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Diarrhoea haemorrhagic * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Diverticulum * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Diverticulum intestinal * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Diverticulum oesophageal * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Duodenal ulcer * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Dyspepsia * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Dysphagia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Gastric haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Gastric perforation * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Gastric ulcer * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Gastric ulcer haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Gastritis * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Gastritis haemorrhagic * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Gastrooesophageal reflux disease * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Gastrointestinal haemorrhage * 1    
# participants affected / at risk     7/2412 (0.29%)     5/2405 (0.21%)  
Haematemesis * 1    
# participants affected / at risk     4/2412 (0.17%)     2/2405 (0.08%)  
Haematochezia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Haemorrhoids * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Hiatus hernia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Ileus * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Inguinal hernia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Intestinal fistula * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Intestinal infarction * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Intestinal obstruction * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Large intestine perforation * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Melaena * 1    
# participants affected / at risk     2/2412 (0.08%)     7/2405 (0.29%)  
Nausea * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Oesophageal ulcer * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Oesophageal ulcer haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pancreatitis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pancreatitis acute * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Rectal haemorrhage * 1    
# participants affected / at risk     6/2412 (0.25%)     6/2405 (0.25%)  
Retroperitoneal haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Small intestinal obstruction * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Small intestinal perforation * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Tooth loss * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Umbilical hernia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Upper gastrointestinal haemorrhage * 1    
# participants affected / at risk     2/2412 (0.08%)     2/2405 (0.08%)  
Vomiting * 1    
# participants affected / at risk     3/2412 (0.12%)     3/2405 (0.12%)  
Intestinal polyp * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Gastrointestinal dysplasia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Subileus * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Lower gastrointestinal haemorrhage * 1    
# participants affected / at risk     2/2412 (0.08%)     3/2405 (0.12%)  
Haemorrhoidal haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Retroperitoneal haematoma * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Intestinal haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     3/2405 (0.12%)  
Abdominal hernia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Large intestinal obstruction * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Abdominal wall haematoma * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
General disorders      
Asthenia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Chest discomfort * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Chest pain * 1    
# participants affected / at risk     21/2412 (0.87%)     27/2405 (1.12%)  
Cyst * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Death * 1    
# participants affected / at risk     4/2412 (0.17%)     2/2405 (0.08%)  
Fatigue * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Gait disturbance * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Granuloma * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Impaired healing * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Malaise * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Multi-organ failure * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Oedema peripheral * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Pyrexia * 1    
# participants affected / at risk     4/2412 (0.17%)     2/2405 (0.08%)  
Sudden death * 1    
# participants affected / at risk     3/2412 (0.12%)     1/2405 (0.04%)  
General physical health deterioration * 1    
# participants affected / at risk     3/2412 (0.12%)     2/2405 (0.08%)  
Adverse drug reaction * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Drug intolerance * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Non-cardiac chest pain * 1    
# participants affected / at risk     6/2412 (0.25%)     3/2405 (0.12%)  
Implant site thrombosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Device deposit issue * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hepatobiliary disorders      
Bile duct stone * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Biliary colic * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cholangitis * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Cholecystitis * 1    
# participants affected / at risk     2/2412 (0.08%)     1/2405 (0.04%)  
Cholecystitis acute * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Cholelithiasis * 1    
# participants affected / at risk     4/2412 (0.17%)     5/2405 (0.21%)  
Hepatic failure * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Hepatic function abnormal * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hepatic pain * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Hepatic steatosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hepatitis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hepatitis acute * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Hepatitis chronic active * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Ischaemic hepatitis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Jaundice * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cytolytic hepatitis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Immune system disorders      
Antiphospholipid syndrome * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Drug hypersensitivity * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hypersensitivity * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Sarcoidosis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Infections and infestations      
Appendicitis * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Bacteraemia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Bronchitis * 1    
# participants affected / at risk     5/2412 (0.21%)     8/2405 (0.33%)  
Bronchopneumonia * 1    
# participants affected / at risk     4/2412 (0.17%)     4/2405 (0.17%)  
Bronchopulmonary aspergillosis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cellulitis * 1    
# participants affected / at risk     4/2412 (0.17%)     5/2405 (0.21%)  
Cystitis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Diverticulitis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Endocarditis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Endocarditis bacterial * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Gastroenteritis * 1    
# participants affected / at risk     3/2412 (0.12%)     0/2405 (0.00%)  
Gastroenteritis salmonella * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Hepatitis A * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Herpes simplex * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Herpes zoster * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Lobar pneumonia * 1    
# participants affected / at risk     4/2412 (0.17%)     1/2405 (0.04%)  
Localised infection * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Lower respiratory tract infection * 1    
# participants affected / at risk     3/2412 (0.12%)     4/2405 (0.17%)  
Lung abscess * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Mastitis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Osteomyelitis * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Pneumonia * 1    
# participants affected / at risk     22/2412 (0.91%)     21/2405 (0.87%)  
Pneumonia mycoplasmal * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pneumonia primary atypical * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Postoperative wound infection * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pyelonephritis * 1    
# participants affected / at risk     3/2412 (0.12%)     2/2405 (0.08%)  
Pyelonephritis acute * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Sepsis * 1    
# participants affected / at risk     13/2412 (0.54%)     2/2405 (0.08%)  
Sinusitis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Skin infection * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Tracheobronchitis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Tuberculosis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Urinary tract infection * 1    
# participants affected / at risk     7/2412 (0.29%)     4/2405 (0.17%)  
Viral rash * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Wound infection * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Urosepsis * 1    
# participants affected / at risk     2/2412 (0.08%)     2/2405 (0.08%)  
Anal abscess * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Neutropenic sepsis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Appendiceal abscess * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Groin abscess * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Abscess limb * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Abscess soft tissue * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Prostate infection * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Skin bacterial infection * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Abscess neck * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pneumonia necrotising * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Subdiaphragmatic abscess * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Infective exacerbation of chronic obstructive airways disease * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Biliary sepsis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Joint abscess * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Wound infection staphylococcal * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Intervertebral discitis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Lung infection * 1    
# participants affected / at risk     3/2412 (0.12%)     4/2405 (0.17%)  
Respiratory tract infection * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Cholecystitis infective * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Device related infection * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Infectious peritonitis * 1    
# participants affected / at risk     4/2412 (0.17%)     0/2405 (0.00%)  
Injury, poisoning and procedural complications      
Alcohol poisoning * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Ankle fracture * 1    
# participants affected / at risk     3/2412 (0.12%)     0/2405 (0.00%)  
Cerebral haemorrhage traumatic * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Concussion * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Facial bones fracture * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Fall * 1    
# participants affected / at risk     4/2412 (0.17%)     1/2405 (0.04%)  
Femoral neck fracture * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Femur fracture * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Fibula fracture * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Foot fracture * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hip fracture * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Humerus fracture * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Joint dislocation * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Kidney rupture * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Multiple injuries * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Operative haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Overdose * 1    
# participants affected / at risk     2/2412 (0.08%)     2/2405 (0.08%)  
Rib fracture * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Road traffic accident * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Soft tissue injury * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Spinal compression fracture * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Splenic haematoma * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Sternal fracture * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Subcutaneous haematoma * 1    
# participants affected / at risk     1/2412 (0.04%)     3/2405 (0.12%)  
Subdural haematoma * 1    
# participants affected / at risk     1/2412 (0.04%)     3/2405 (0.12%)  
Subdural haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     3/2405 (0.12%)  
Tendon rupture * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Tibia fracture * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Traumatic haematoma * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Anaemia postoperative * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Vascular pseudoaneurysm * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Perirenal haematoma * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Traumatic fracture * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cervical vertebral fracture * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Lumbar vertebral fracture * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Thoracic vertebral fracture * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Contusion * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Post procedural haemorrhage * 1    
# participants affected / at risk     2/2412 (0.08%)     3/2405 (0.12%)  
Incision site haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Brain contusion * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Cardiac valve replacement complication * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Postoperative ileus * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Procedural complication * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Joint injury * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Limb injury * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Chest injury * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Upper limb fracture * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Toxicity to various agents * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Craniocerebral injury * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Investigations      
Activated partial thromboplastin time prolonged * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Alanine aminotransferase increased * 1    
# participants affected / at risk     6/2412 (0.25%)     9/2405 (0.37%)  
Aspartate aminotransferase increased * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Blood amylase increased * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Blood potassium increased * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
C-reactive protein increased * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Coagulation time prolonged * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Coagulation time shortened * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Gamma-glutamyltransferase increased * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Haemoglobin decreased * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
International normalised ratio abnormal * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
International normalised ratio increased * 1    
# participants affected / at risk     1/2412 (0.04%)     4/2405 (0.17%)  
Liver function test abnormal * 1    
# participants affected / at risk     4/2412 (0.17%)     9/2405 (0.37%)  
Prostatic specific antigen increased * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Ultrasound liver abnormal * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Ejection fraction decreased * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Medical observation * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Transaminases increased * 1    
# participants affected / at risk     2/2412 (0.08%)     2/2405 (0.08%)  
Hepatic enzyme increased * 1    
# participants affected / at risk     3/2412 (0.12%)     1/2405 (0.04%)  
Metabolism and nutrition disorders      
Acidosis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Dehydration * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Diabetes mellitus * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Failure to thrive * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Gout * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hypercalcaemia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hyperglycaemia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Hyperkalaemia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hypoalbuminaemia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hypocalcaemia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hypoglycaemia * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Hypokalaemia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hyponatraemia * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Hypovolaemia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Shock hypoglycaemic * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Metabolic disorder * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Malnutrition * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Decreased appetite * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Type 2 diabetes mellitus * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Musculoskeletal and connective tissue disorders      
Arthralgia * 1    
# participants affected / at risk     2/2412 (0.08%)     2/2405 (0.08%)  
Back pain * 1    
# participants affected / at risk     5/2412 (0.21%)     6/2405 (0.25%)  
Bone pain * 1    
# participants affected / at risk     0/2412 (0.00%)     3/2405 (0.12%)  
Cervical spinal stenosis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Groin pain * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Haemarthrosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Joint stiffness * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Muscle haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     9/2405 (0.37%)  
Muscle twitching * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Muscular weakness * 1    
# participants affected / at risk     4/2412 (0.17%)     3/2405 (0.12%)  
Musculoskeletal pain * 1    
# participants affected / at risk     3/2412 (0.12%)     1/2405 (0.04%)  
Myalgia * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Osteoarthritis * 1    
# participants affected / at risk     4/2412 (0.17%)     6/2405 (0.25%)  
Osteolysis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Osteonecrosis * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Pain in extremity * 1    
# participants affected / at risk     4/2412 (0.17%)     1/2405 (0.04%)  
Rheumatoid arthritis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Rotator cuff syndrome * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Scoliosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Spinal column stenosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Spinal osteoarthritis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Systemic lupus erythematosus * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Temporomandibular joint syndrome * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pseudarthrosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Musculoskeletal chest pain * 1    
# participants affected / at risk     3/2412 (0.12%)     1/2405 (0.04%)  
Intervertebral disc compression * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Intervertebral disc degeneration * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Spinal disorder * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Intervertebral disc disorder * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Acute lymphocytic leukaemia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Acute promyelocytic leukaemia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Adenocarcinoma * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
B-cell lymphoma * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Basal cell carcinoma * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Benign oesophageal neoplasm * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Bile duct cancer non-resectable * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Bladder cancer * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Bladder neoplasm * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Breast cancer * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Breast cancer recurrent * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Breast neoplasm * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Bronchial carcinoma * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Cervix carcinoma * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Colon cancer * 1    
# participants affected / at risk     8/2412 (0.33%)     1/2405 (0.04%)  
Fibroadenoma of breast * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Gallbladder cancer * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Gastric cancer * 1    
# participants affected / at risk     3/2412 (0.12%)     0/2405 (0.00%)  
Glioblastoma multiforme * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Lung adenocarcinoma * 1    
# participants affected / at risk     3/2412 (0.12%)     4/2405 (0.17%)  
Lung carcinoma cell type unspecified recurrent * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Lung squamous cell carcinoma stage unspecified * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Lymphoma * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Malignant ascites * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Malignant melanoma * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Malignant pleural effusion * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Meningioma * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Mesothelioma malignant * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Metastases to liver * 1    
# participants affected / at risk     2/2412 (0.08%)     4/2405 (0.17%)  
Metastases to lung * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Metastases to lymph nodes * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Metastases to pleura * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Metastases to spine * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Multiple myeloma * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Myelodysplastic syndrome * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Myelofibrosis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Neoplasm malignant * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Neoplasm prostate * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Ovarian cancer * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Ovarian germ cell teratoma benign * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Pancreatic carcinoma * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Pancreatic carcinoma metastatic * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Parathyroid tumour benign * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Polycythaemia vera * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Prostate cancer recurrent * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Prostatic adenoma * 1    
# participants affected / at risk     2/2412 (0.08%)     2/2405 (0.08%)  
Rectal cancer * 1    
# participants affected / at risk     2/2412 (0.08%)     1/2405 (0.04%)  
Renal cancer * 1    
# participants affected / at risk     1/2412 (0.04%)     3/2405 (0.12%)  
Small cell lung cancer stage unspecified * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Squamous cell carcinoma of skin * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
T-cell lymphoma * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Uterine leiomyoma * 1    
# participants affected / at risk     4/2412 (0.17%)     2/2405 (0.08%)  
Histiocytosis haematophagic * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Tumour haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Lung cancer metastatic * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Gastrointestinal stromal tumour * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Metastases to peritoneum * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Rectal cancer metastatic * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Breast cancer metastatic * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Colon cancer metastatic * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Lung neoplasm malignant * 1    
# participants affected / at risk     5/2412 (0.21%)     4/2405 (0.17%)  
Metastases to central nervous system * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Prostate cancer * 1    
# participants affected / at risk     3/2412 (0.12%)     7/2405 (0.29%)  
Brain neoplasm * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Colon neoplasm * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Mantle cell lymphoma * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Metastatic neoplasm * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Ovarian epithelial cancer * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Pelvic neoplasm * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Colorectal cancer * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Renal neoplasm * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Adrenal neoplasm * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Extranodal marginal zone B-cell lymphoma (MALT type) * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Non-small cell lung cancer * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Gastric neoplasm * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Lung neoplasm * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Rectal neoplasm * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Metastasis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Metastatic gastric cancer * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Thyroid cancer * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Renal cell carcinoma * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Inflammatory pseudotumour * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Nervous system disorders      
Altered state of consciousness * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Amyotrophic lateral sclerosis * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Ataxia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Carotid artery stenosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Cauda equina syndrome * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cerebellar haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cerebral haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     4/2405 (0.17%)  
Cerebral infarction * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Cerebrovascular accident * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Clumsiness * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Coma * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Convulsion * 1    
# participants affected / at risk     2/2412 (0.08%)     3/2405 (0.12%)  
Dementia Alzheimer's type * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Depressed level of consciousness * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Dizziness * 1    
# participants affected / at risk     3/2412 (0.12%)     3/2405 (0.12%)  
Encephalopathy * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Epilepsy * 1    
# participants affected / at risk     2/2412 (0.08%)     1/2405 (0.04%)  
Guillain-Barre syndrome * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Haemorrhage intracranial * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Headache * 1    
# participants affected / at risk     3/2412 (0.12%)     4/2405 (0.17%)  
Hepatic encephalopathy * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Leukoencephalopathy * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Loss of consciousness * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Migraine * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Nervous system disorder * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Neuropathy peripheral * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Parkinsonism * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Presyncope * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Sciatica * 1    
# participants affected / at risk     2/2412 (0.08%)     1/2405 (0.04%)  
Spinal cord compression * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Subarachnoid haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Syncope * 1    
# participants affected / at risk     8/2412 (0.33%)     6/2405 (0.25%)  
Tension headache * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Transient ischaemic attack * 1    
# participants affected / at risk     3/2412 (0.12%)     3/2405 (0.12%)  
Balance disorder * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
VIIth nerve paralysis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Lacunar infarction * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Haemorrhagic transformation stroke * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Cerebrovascular insufficiency * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Radicular pain * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Ischaemic stroke * 1    
# participants affected / at risk     13/2412 (0.54%)     5/2405 (0.21%)  
Parkinson's disease * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Complex regional pain syndrome * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pregnancy, puerperium and perinatal conditions      
Post abortion haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pregnancy * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Psychiatric disorders      
Alcohol abuse * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Alcoholism * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Anxiety * 1    
# participants affected / at risk     5/2412 (0.21%)     3/2405 (0.12%)  
Bipolar I disorder * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Confusional state * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Delusion * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Depression * 1    
# participants affected / at risk     4/2412 (0.17%)     3/2405 (0.12%)  
Mania * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Panic attack * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Suicide attempt * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Mental status changes * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Somatoform disorder * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Mental disorder * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Mental disorder due to a general medical condition * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Renal and urinary disorders      
Acute prerenal failure * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Anuria * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Bladder dilatation * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Dysuria * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Glomerulonephritis membranous * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Haematuria * 1    
# participants affected / at risk     8/2412 (0.33%)     11/2405 (0.46%)  
Nephritis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Nephrolithiasis * 1    
# participants affected / at risk     0/2412 (0.00%)     3/2405 (0.12%)  
Nephropathy toxic * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Nephrotic syndrome * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Renal colic * 1    
# participants affected / at risk     0/2412 (0.00%)     3/2405 (0.12%)  
Renal cyst * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Renal failure acute * 1    
# participants affected / at risk     2/2412 (0.08%)     4/2405 (0.17%)  
Urinary retention * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Urinary tract disorder * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Urinary bladder polyp * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Renal mass * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Renal impairment * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Urethral stenosis * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Reproductive system and breast disorders      
Benign prostatic hyperplasia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Cervical dysplasia * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Cervical polyp * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Dysfunctional uterine bleeding * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Menorrhagia * 1    
# participants affected / at risk     9/2412 (0.37%)     2/2405 (0.08%)  
Metrorrhagia * 1    
# participants affected / at risk     4/2412 (0.17%)     2/2405 (0.08%)  
Ovarian cyst * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Priapism * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Prostatitis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Uterine polyp * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Uterine prolapse * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Vaginal haemorrhage * 1    
# participants affected / at risk     4/2412 (0.17%)     0/2405 (0.00%)  
Vulval disorder * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Genital haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Prostatic mass * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Respiratory, thoracic and mediastinal disorders      
Acute pulmonary oedema * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Acute respiratory distress syndrome * 1    
# participants affected / at risk     2/2412 (0.08%)     1/2405 (0.04%)  
Acute respiratory failure * 1    
# participants affected / at risk     1/2412 (0.04%)     4/2405 (0.17%)  
Asthma * 1    
# participants affected / at risk     4/2412 (0.17%)     2/2405 (0.08%)  
Bronchial obstruction * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Bronchiectasis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Bronchospasm * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Chronic obstructive pulmonary disease * 1    
# participants affected / at risk     9/2412 (0.37%)     5/2405 (0.21%)  
Cough * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Dyspnoea * 1    
# participants affected / at risk     17/2412 (0.70%)     13/2405 (0.54%)  
Emphysema * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Epistaxis * 1    
# participants affected / at risk     3/2412 (0.12%)     2/2405 (0.08%)  
Haemoptysis * 1    
# participants affected / at risk     6/2412 (0.25%)     8/2405 (0.33%)  
Haemothorax * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Hyperventilation * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Interstitial lung disease * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Lung disorder * 1    
# participants affected / at risk     3/2412 (0.12%)     2/2405 (0.08%)  
Pharyngeal cyst * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pleural effusion * 1    
# participants affected / at risk     9/2412 (0.37%)     11/2405 (0.46%)  
Pleurisy * 1    
# participants affected / at risk     0/2412 (0.00%)     4/2405 (0.17%)  
Pleuritic pain * 1    
# participants affected / at risk     4/2412 (0.17%)     8/2405 (0.33%)  
Pneumothorax * 1    
# participants affected / at risk     1/2412 (0.04%)     3/2405 (0.12%)  
Pulmonary congestion * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Pulmonary embolism * 1    
# participants affected / at risk     6/2412 (0.25%)     1/2405 (0.04%)  
Pulmonary fibrosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pulmonary haemorrhage * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Pulmonary hypertension * 1    
# participants affected / at risk     4/2412 (0.17%)     1/2405 (0.04%)  
Pulmonary infarction * 1    
# participants affected / at risk     3/2412 (0.12%)     2/2405 (0.08%)  
Pulmonary oedema * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Pulmonary venous thrombosis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Respiratory arrest * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Respiratory failure * 1    
# participants affected / at risk     3/2412 (0.12%)     5/2405 (0.21%)  
Sleep apnoea syndrome * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Mediastinal haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Pulmonary arterial hypertension * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Skin and subcutaneous tissue disorders      
Angioedema * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Dermatitis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Dermatitis exfoliative * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Dermatomyositis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Drug eruption * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Haemorrhage subcutaneous * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hyperkeratosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Lichen planus * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Purpura * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Rash morbilliform * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Skin lesion * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Skin necrosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Skin ulcer * 1    
# participants affected / at risk     1/2412 (0.04%)     1/2405 (0.04%)  
Urticaria * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Social circumstances      
Miscarriage of partner * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Surgical and medical procedures      
Abortion induced * 1    
# participants affected / at risk     2/2412 (0.08%)     3/2405 (0.12%)  
Vascular disorders      
Aortic aneurysm * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Aortic aneurysm rupture * 1    
# participants affected / at risk     0/2412 (0.00%)     2/2405 (0.08%)  
Aortic dissection * 1    
# participants affected / at risk     2/2412 (0.08%)     0/2405 (0.00%)  
Aortic thrombosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Circulatory collapse * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Embolism arterial * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Haematoma * 1    
# participants affected / at risk     4/2412 (0.17%)     4/2405 (0.17%)  
Hypertension * 1    
# participants affected / at risk     1/2412 (0.04%)     3/2405 (0.12%)  
Hypertensive crisis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Hypotension * 1    
# participants affected / at risk     3/2412 (0.12%)     1/2405 (0.04%)  
Hypovolaemic shock * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Iliac artery thrombosis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Orthostatic hypotension * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Peripheral ischaemia * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Temporal arteritis * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Thrombophlebitis superficial * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Vena cava thrombosis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Lymphocele * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Intra-abdominal haematoma * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Varicophlebitis * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Arterial haemorrhage * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
Intra-abdominal haemorrhage * 1    
# participants affected / at risk     1/2412 (0.04%)     2/2405 (0.08%)  
Paradoxical embolism * 1    
# participants affected / at risk     1/2412 (0.04%)     0/2405 (0.00%)  
Distributive shock * 1    
# participants affected / at risk     0/2412 (0.00%)     1/2405 (0.04%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 14.1




  Other Adverse Events


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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:

Publications automatically indexed to this study:

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00439777     History of Changes
Other Study ID Numbers: 11702b, 2006-004495-13
Study First Received: February 23, 2007
Results First Received: November 22, 2012
Last Updated: January 25, 2014
Health Authority: Andorra: Ministeri de Salut i Benestar
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Ethikkommission
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ethics Committee
Brazil: National Committee of Ethics in Research
Brazil: National Health Surveillance Agency
Canada: Ethics Review Committee
Canada: Health Canada
China: Ethics Committee
China: Food and Drug Administration
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Denmark: Ethics Committee
Estonia: The State Agency of Medicine
European Union: European Medicines Agency
Finland: Ethics Committee
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Hong Kong: Department of Health
Hong Kong: Ethics Committee
Hungary: Institutional Ethics Committee
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
India: Institutional Review Board
Indonesia: National Agency of Drug and Food Control
Ireland: Irish Medicines Board
Ireland: Research Ethics Committee
Israel: Ethics Commission
Israel: Ministry of Health
Italy: Ethics Committee
Italy: National Institute of Health
Latvia: Institutional Review Board
Latvia: State Agency of Medicines
Lithuania: Bioethics Committee
Lithuania: State Medicine Control Agency - Ministry of Health
Malaysia: The National Pharmaceutical Control Bureau (NPCB)
Netherlands: Independent Ethics Committee
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Health and Disability Ethics Committees
New Zealand: Medsafe
Norway: Ethics Committee
Norway: Norwegian Medicines Agency
Peru: Ethics Committee
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Peru: Instituto Nacional de Salud
Peru: Ministry of Health
Philippines: Bureau of Food and Drugs
Philippines: Ethics Committee
Poland: Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: Health Ethic Committee
Portugal: National Pharmacy and Medicines Institute
Singapore: Health Sciences Authority
Slovakia: State Institute for Drug Control
South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council
South Africa: National Health Research Ethics Council
South Korea: Institutional Review Board
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Ethics Committee
Spain: Spanish Agency of Medicines
Sweden: Institutional Review Board
Sweden: Medical Products Agency
Switzerland: Ethikkommission
Switzerland: Swissmedic
Taiwan: Center for Drug Evaluation
Taiwan: Institutional Review Board
Thailand: Ethical Committee
Thailand: Food and Drug Administration
Thailand: National Research Council of Thailand (NCRT)
Thailand: Medical Council of Thailand (MCT)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
United States: Food and Drug Administration
United States: Institutional Review Board