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VA NEPHRON-D: Diabetes iN Nephropathy Study (VA NEPHRON-D)

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: NCT00555217
Recruitment Status : Terminated (It was stopped primarily because of safety concerns along with low conditional power to detect a treatment effect on the primary outcome.)
First Posted : November 8, 2007
Results First Posted : May 29, 2015
Last Update Posted : May 29, 2015
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Care Provider);   Primary Purpose: Treatment
Conditions Kidney Disease
Nephropathy
Type 2 Diabetes
Interventions Drug: losartan
Drug: lisinopril
Enrollment 1448
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Combination of ARB and ACEI Monotherapy ARB
Hide Arm/Group Description

Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB)

losartan: 50 or 100mg/day

lisinopril: 10, 20 or 40 mg/day

Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB)

losartan: 50 or 100mg/day

Period Title: Overall Study
Started 724 724
Completed 649 656
Not Completed 75 68
Reason Not Completed
Withdrawal by Subject             35             31
Lost to Follow-up             19             20
close out sites             21             17
Arm/Group Title Combination of ARB and ACEI Monotherapy ARB Total
Hide Arm/Group Description

Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB)

losartan: 50 or 100mg/day

lisinopril: 10, 20 or 40 mg/day

Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB)

losartan: 50 or 100mg/day

Total of all reporting groups
Overall Number of Baseline Participants 724 724 1448
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 724 participants 724 participants 1448 participants
64.5  (7.9) 64.7  (7.7) 64.6  (7.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 724 participants 724 participants 1448 participants
Female
9
   1.2%
3
   0.4%
12
   0.8%
Male
715
  98.8%
721
  99.6%
1436
  99.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 724 participants 724 participants 1448 participants
Hispanic or Latino
71
   9.8%
75
  10.4%
146
  10.1%
Not Hispanic or Latino
653
  90.2%
649
  89.6%
1302
  89.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 724 participants 724 participants 1448 participants
American Indian or Alaska Native
16
   2.2%
25
   3.5%
41
   2.8%
Asian
4
   0.6%
6
   0.8%
10
   0.7%
Native Hawaiian or Other Pacific Islander
8
   1.1%
5
   0.7%
13
   0.9%
Black or African American
172
  23.8%
160
  22.1%
332
  22.9%
White
523
  72.2%
514
  71.0%
1037
  71.6%
More than one race
0
   0.0%
14
   1.9%
14
   1.0%
Unknown or Not Reported
1
   0.1%
0
   0.0%
1
   0.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 724 participants 724 participants 1448 participants
724 724 1448
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 724 participants 724 participants 1448 participants
34.9  (6.7) 34.3  (6.9) 34.6  (6.8)
Coronary Artery Disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 724 participants 724 participants 1448 participants
Yes 159 167 326
No 565 557 1122
Congestive Heart Failure  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 724 participants 724 participants 1448 participants
Yes 116 110 226
No 608 614 1222
Retinopathy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 724 participants 724 participants 1448 participants
Yes 309 310 619
No 415 414 829
SBP  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 724 participants 724 participants 1448 participants
136.9  (16.5) 137.0  (16.0) 136.9  (16.3)
DBP  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 724 participants 724 participants 1448 participants
72.5  (10.6) 72.8  (9.9) 72.7  (10.2)
Total Cholesterol  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 724 participants 724 participants 1448 participants
157.9  (43.6) 159.0  (40.5) 158.4  (42.1)
LDL cholesterol  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 724 participants 724 participants 1448 participants
81.6  (32.4) 84.3  (35.0) 82.9  (33.7)
HDL cholesterol  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 724 participants 724 participants 1448 participants
37.7  (11.0) 38.7  (11.3) 38.2  (11.2)
Triglycerides  
Median (Inter-Quartile Range)
Unit of measure:  Mg/dl
Number Analyzed 724 participants 724 participants 1448 participants
165
(111 to 260)
162
(111 to 235)
163
(111 to 249)
HbA1c  
Mean (Standard Deviation)
Unit of measure:  %
Number Analyzed 724 participants 724 participants 1448 participants
7.8  (1.2) 7.8  (1.3) 7.8  (1.3)
serum Creatinine at enrollment  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 724 participants 724 participants 1448 participants
1.5  (0.4) 1.5  (0.4) 1.5  (0.4)
Potassium  
Mean (Standard Deviation)
Unit of measure:  meq/L
Number Analyzed 724 participants 724 participants 1448 participants
4.3  (0.5) 4.3  (0.5) 4.3  (0.5)
eGFR at enrollment  
Mean (Standard Deviation)
Unit of measure:  Ml/min/1.73m^2
Number Analyzed 724 participants 724 participants 1448 participants
53.6  (15.5) 53.7  (16.2) 53.7  (15.9)
urine albumin/creatinine at enrollment  
Median (Inter-Quartile Range)
Unit of measure:  Mg/g
Number Analyzed 724 participants 724 participants 1448 participants
841.5
(495 to 1698)
861.5
(487.5 to 1789)
851.0
(490 to 1752)
1.Primary Outcome
Title A Composite Endpoint of Reduction in Estimated GFR of 30ml/Min/1.73m*m in Individuals w/a Baseline Estimated GFR >= 60 ml/Min/1.73m*m, Reduction in Estimated GFR >50% in Individuals w/ Baseline Estimated GFR <60ml/Min/1.73m*m; ESRD or Death
Hide Description Time to the first event of reduction in estimated GFR of 30ml/min/1.73m*m in individuals w/a baseline estimated GFR >= 60 ml/min/1.73m*m, reduction in estimated GFR >50% in individuals w/ baseline estimated GFR <60ml/min/1.73m*m; ESRD or death.
Time Frame From enrollemnt to time of first primary event, up to 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination of ARB and ACEI Monotherapy ARB
Hide Arm/Group Description:
Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB)
Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB)
Overall Number of Participants Analyzed 724 724
Measure Type: Number
Unit of Measure: participants
132 152
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination of ARB and ACEI, Monotherapy ARB
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.70 to 1.12
Estimation Comments Combination ARB and ACEI vs. mono therapy ARB
2.Secondary Outcome
Title A Renal Composite Endpoint, Defined as; Reduction in Estimated GFR of >50% (for Individuals With Baseline GFR <60) or Reduction in GFR of >30 (for Individuals With Baseline GFR >= GFR 60) or ESRD.
Hide Description Time to the first event of reduction in estimated GFR of >50% (for individuals with baseline GFR <60) or reduction in GFR of >30 (for individuals with baseline GFR >= GFR 60) or ESRD.
Time Frame From enrollment to time of first event, up to 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination of ARB and ACEI Monotherapy ARB
Hide Arm/Group Description:
Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB)
Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB)
Overall Number of Participants Analyzed 724 724
Measure Type: Number
Unit of Measure: participants
77 101
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination of ARB and ACEI, Monotherapy ARB
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.58 to 1.05
Estimation Comments Combination ARB and ACEI vs. mono therapy ARB
Time Frame July 2008 - January 2013
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Combination of ARB and ACEI Monotherapy ARB
Hide Arm/Group Description Combination of an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) Mono therapy arm. Standard treatment with angiotensin receptor blocker (ARB)
All-Cause Mortality
Combination of ARB and ACEI Monotherapy ARB
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Combination of ARB and ACEI Monotherapy ARB
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   416/724 (57.46%)      380/724 (52.49%)    
Blood and lymphatic system disorders     
Anaemia of chronic disease  1  0/724 (0.00%)  0 1/724 (0.14%)  2
Anaemia of malignant disease  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Anemia  2  15/724 (2.07%)  23 12/724 (1.66%)  13
Coagulopathy  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Idiopathic thrombocytopenic pu  2  0/724 (0.00%)  0 1/724 (0.14%)  3
Iron deficiency anaemia  2  2/724 (0.28%)  3 3/724 (0.41%)  3
Leukocytosis  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Normochromic normocytic anaemi  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Pancytopenia  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Thrombocytopenia  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Cardiac disorders     
Acute coronary syndrome  2  3/724 (0.41%)  3 7/724 (0.97%)  8
Acute myocardial infarction  2  27/724 (3.73%)  31 24/724 (3.31%)  25
Angina pectoris  2  7/724 (0.97%)  8 9/724 (1.24%)  11
Angina unstable  2  4/724 (0.55%)  4 2/724 (0.28%)  2
Arrhythmia  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Atrial fibrillation  2  13/724 (1.80%)  18 14/724 (1.93%)  19
Atrial flutter  2  5/724 (0.69%)  5 3/724 (0.41%)  3
Atrioventricular block  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Atrioventricular block complet  2  3/724 (0.41%)  3 4/724 (0.55%)  4
Atrioventricular block first d  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Atrioventricular block second  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Bradycardia  2  8/724 (1.10%)  8 6/724 (0.83%)  6
Bundle branch block right  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Cardiac arrest  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Cardiac failure  2  7/724 (0.97%)  8 6/724 (0.83%)  6
Cardiac failure acute  2  2/724 (0.28%)  2 3/724 (0.41%)  4
Cardiac failure chronic  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Cardiac failure congestive  2  80/724 (11.05%)  143 95/724 (13.12%)  155
Cardiac tamponade  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Cardio-respiratory arrest  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Cardiogenic shock  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Cardiomyopathy  2  2/724 (0.28%)  3 2/724 (0.28%)  2
Cardiorenal syndrome  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Cardiovascular disorder  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Coronary artery disease  2  32/724 (4.42%)  35 23/724 (3.18%)  26
Coronary artery occlusion  2  6/724 (0.83%)  7 4/724 (0.55%)  4
Coronary artery stenosis  2  7/724 (0.97%)  7 7/724 (0.97%)  7
Coronary artery thrombosis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Diastolic dysfunction  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Hypertensive heart disease  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Intracardiac thrombus  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Ischaemic cardiomyopathy  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Mitral valve incompetence  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Myocardial infarction  2  18/724 (2.49%)  18 15/724 (2.07%)  17
Myocardial ischaemia  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Nodal arrhythmia  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Nodal rhythm  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Pericardial effusion  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Pericarditis  2  0/724 (0.00%)  0 2/724 (0.28%)  3
Rhythm idioventricular  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Right ventricular failure  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Sick sinus syndrome  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Sinus bradycardia  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Supraventricular tachycardia  2  3/724 (0.41%)  3 1/724 (0.14%)  1
Tachycardia  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Trifascicular block  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Ventricular tachycardia  2  1/724 (0.14%)  2 0/724 (0.00%)  0
Congenital, familial and genetic disorders     
Haemorrhagic arteriovenous mal  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Ear and labyrinth disorders     
Cerumen impaction  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Meniere's disease  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Vertigo  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Vertigo positional  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Endocrine disorders     
Adrenal mass  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Goitre  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Hyperparathyroidism  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Eye disorders     
Amaurosis fugax  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Cataract  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Conjunctivitis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Diplopia  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Glaucoma  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Iridocyclitis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Retinal detachment  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Visual acuity reduced  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  2  4/724 (0.55%)  4 2/724 (0.28%)  2
Abdominal pain upper  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Abdominal wall haematoma  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Abdominal wall haemorrhage  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Ascites  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Colitis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Colonic polyp  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Colonic pseudo-obstruction  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Constipation  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Diarrhoea  2  10/724 (1.38%)  11 4/724 (0.55%)  4
Diverticulum intestinal  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Diverticulum intestinal haemor  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Duodenal ulcer  2  3/724 (0.41%)  3 0/724 (0.00%)  0
Dyspepsia  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Enterocolitis haemorrhagic  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Flatulence  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Gastric ulcer  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Gastric varices haemorrhage  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Gastritis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Gastritis haemorrhagic  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Gastrointestinal haemorrhage  2  14/724 (1.93%)  17 5/724 (0.69%)  5
Gastrointestinal oedema  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Gastrointestinal ulcer haemorr  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Gastrooesophageal reflux disea  2  1/724 (0.14%)  1 2/724 (0.28%)  2
Haemorrhoids  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Ileus  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Impaired gastric emptying  2  2/724 (0.28%)  5 0/724 (0.00%)  0
Intestinal mass  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Intestinal obstruction  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Intestinal perforation  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Intestinal polyp haemorrhage  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Large intestinal ulcer  2  1/724 (0.14%)  2 0/724 (0.00%)  0
Lower gastrointestinal haemorr  2  2/724 (0.28%)  2 2/724 (0.28%)  2
Oesophageal spasm  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Oesophagitis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Pancreatitis  2  4/724 (0.55%)  4 2/724 (0.28%)  4
Pancreatitis acute  2  1/724 (0.14%)  2 2/724 (0.28%)  2
Pancreatitis chronic  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Peritoneal perforation  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Pneumatosis intestinalis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Rectal haemorrhage  2  0/724 (0.00%)  0 3/724 (0.41%)  3
Retroperitoneal haematoma  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Retroperitoneal haemorrhage  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Small intestinal obstruction  2  7/724 (0.97%)  7 2/724 (0.28%)  4
Small intestinal perforation  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Swollen tongue  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Umbilical hernia  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Upper gastrointestinal haemorr  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Vomiting  2  4/724 (0.55%)  4 3/724 (0.41%)  3
General disorders     
Adverse drug reaction  2  4/724 (0.55%)  5 2/724 (0.28%)  2
Asthenia  2  1/724 (0.14%)  1 2/724 (0.28%)  2
Chest discomfort  2  0/724 (0.00%)  0 3/724 (0.41%)  3
Chest pain  2  24/724 (3.31%)  27 21/724 (2.90%)  26
Death  2  25/724 (3.45%)  25 13/724 (1.80%)  13
Device malfunction  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Disease progression  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Hernia  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Hernia obstructive  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Hypothermia  2  0/724 (0.00%)  0 1/724 (0.14%)  2
Impaired healing  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Medical device complication  2  3/724 (0.41%)  3 0/724 (0.00%)  0
Non-cardiac chest pain  2  7/724 (0.97%)  7 6/724 (0.83%)  6
Oedema  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Oedema peripheral  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Pain  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Pyrexia  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Sudden cardiac death  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Swelling  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Systemic inflammatory response  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Hepatobiliary disorders     
Bile duct stone  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Cholecystitis  2  0/724 (0.00%)  0 3/724 (0.41%)  3
Cholecystitis acute  2  4/724 (0.55%)  4 1/724 (0.14%)  1
Cholelithiasis  2  4/724 (0.55%)  4 4/724 (0.55%)  4
Gallbladder disorder  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Hepatic congestion  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Portal vein thrombosis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Immune system disorders     
Amyloidosis  2  0/724 (0.00%)  0 1/724 (0.14%)  2
Drug hypersensitivity  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Infections and infestations     
Abscess limb  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Appendicitis  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Appendicitis perforated  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Arthritis bacterial  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Bacteraemia  2  4/724 (0.55%)  4 0/724 (0.00%)  0
Bacterial infection  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Bacterial pyelonephritis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Bronchitis  2  3/724 (0.41%)  3 4/724 (0.55%)  4
Bronchitis bacterial  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Candidiasis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Cellulitis  2  33/724 (4.56%)  46 31/724 (4.28%)  39
Cellulitis staphylococcal  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Clostridial infection  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Clostridium difficile colitis  2  6/724 (0.83%)  6 2/724 (0.28%)  2
Device related infection  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Diverticulitis  2  2/724 (0.28%)  2 2/724 (0.28%)  2
Ear infection  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Emphysematous pyelonephritis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Enterobacter bacteraemia  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Epiglottitis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Escherichia bacteraemia  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Escherichia infection  2  2/724 (0.28%)  2 0/724 (0.00%)  0
External ear cellulitis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Gangrene  2  6/724 (0.83%)  7 4/724 (0.55%)  5
Gastroenteritis  2  9/724 (1.24%)  10 4/724 (0.55%)  4
Gastroenteritis clostridial  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Gastroenteritis viral  2  0/724 (0.00%)  0 3/724 (0.41%)  3
Graft infection  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Groin abscess  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Haemophilus infection  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Herpes zoster  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Infected bites  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Infected skin ulcer  2  3/724 (0.41%)  4 1/724 (0.14%)  1
Infection  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Influenza  2  1/724 (0.14%)  1 2/724 (0.28%)  2
Intervertebral discitis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Labyrinthitis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Lobar pneumonia  2  6/724 (0.83%)  6 5/724 (0.69%)  5
Localised infection  2  2/724 (0.28%)  3 1/724 (0.14%)  1
Lymphangitis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Nosocomial infection  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Oesophageal candidiasis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Orchitis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Osteomyelitis  2  13/724 (1.80%)  17 13/724 (1.80%)  15
Osteomyelitis acute  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Osteomyelitis chronic  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Otitis media  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Peptostreptococcus infection  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Perirectal abscess  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pertussis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pneumonia  2  43/724 (5.94%)  50 41/724 (5.66%)  43
Pneumonia bacterial  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pneumonia influenzal  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Pneumonia klebsiella  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Pneumonia legionella  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Pneumonia staphylococcal  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pneumonia streptococcal  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Post procedural infection  2  3/724 (0.41%)  3 1/724 (0.14%)  1
Postoperative wound infection  2  3/724 (0.41%)  3 0/724 (0.00%)  0
Pseudomonas infection  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Pyelonephritis  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Respiratory tract infection  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Scrotal abscess  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Sepsis  2  5/724 (0.69%)  5 3/724 (0.41%)  3
Sepsis syndrome  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Septic shock  2  1/724 (0.14%)  2 2/724 (0.28%)  2
Staphylococcal infection  2  6/724 (0.83%)  6 4/724 (0.55%)  4
Staphylococcal sepsis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Streptococcal bacteraemia  2  1/724 (0.14%)  2 0/724 (0.00%)  0
Subcutaneous abscess  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Subdural empyema  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Tinea pedis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Upper respiratory tract infect  2  2/724 (0.28%)  2 2/724 (0.28%)  2
Urinary tract infection  2  14/724 (1.93%)  16 9/724 (1.24%)  10
Urosepsis  2  3/724 (0.41%)  3 2/724 (0.28%)  2
Viral cardiomyopathy  2  0/724 (0.00%)  0 1/724 (0.14%)  1
West Nile viral infection  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Wound infection  2  4/724 (0.55%)  5 1/724 (0.14%)  1
Wound infection staphylococcal  2  0/724 (0.00%)  0 2/724 (0.28%)  2
Injury, poisoning and procedural complications     
Accident at home  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Accident at work  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Accidental overdose  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Animal bite  2  3/724 (0.41%)  3 0/724 (0.00%)  0
Ankle fracture  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Arteriovenous fistula site com  2  3/724 (0.41%)  3 1/724 (0.14%)  1
Arteriovenous fistula thrombos  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Arthropod bite  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Cardiac procedure complication  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Contrast media reaction  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Coronary artery restenosis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Fall  2  17/724 (2.35%)  18 20/724 (2.76%)  22
Femur fracture  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Foreign body  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Gastroenteritis radiation  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Head injury  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Heat stroke  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Hip fracture  2  0/724 (0.00%)  0 1/724 (0.14%)  1
In-stent coronary artery reste  2  4/724 (0.55%)  4 1/724 (0.14%)  1
Incorrect dose administered  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Injury  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Limb injury  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Lower limb fracture  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Medication error  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Overdose  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Patella fracture  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Post procedural complication  2  6/724 (0.83%)  6 5/724 (0.69%)  5
Post procedural haematoma  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Post procedural haemorrhage  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Postoperative fever  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Postoperative wound complicati  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Procedural complication  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Procedural hypertension  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Procedural vomiting  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Radiation dysphagia  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Radiation pneumonitis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Road traffic accident  2  2/724 (0.28%)  2 9/724 (1.24%)  11
Spinal compression fracture  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Subdural haematoma  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Subdural haemorrhage  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Toxicity to various agents  2  1/724 (0.14%)  1 2/724 (0.28%)  2
Vascular graft complication  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Vascular graft occlusion  2  1/724 (0.14%)  2 1/724 (0.14%)  1
Vascular pseudoaneurysm  2  1/724 (0.14%)  2 0/724 (0.00%)  0
Wound dehiscence  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Investigations     
Antibiotic resistant Staphyloc  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Anticoagulation drug level abo  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Anticoagulation drug level bel  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Biopsy kidney  2  0/724 (0.00%)  0 2/724 (0.28%)  2
Biopsy lung  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Blood bicarbonate decreased  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Blood creatine phosphokinase i  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Blood creatinine increased  2  2/724 (0.28%)  2 3/724 (0.41%)  3
Blood glucose decreased  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Blood glucose increased  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Blood potassium increased  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Electrocardiogram change  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Fistulogram  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Heart rate irregular  2  0/724 (0.00%)  0 1/724 (0.14%)  1
International normalised ratio  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Metabolism and nutrition disorders     
Dehydration  2  7/724 (0.97%)  7 3/724 (0.41%)  3
Diabetes mellitus inadequate c  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Diabetic ketoacidosis  2  3/724 (0.41%)  3 1/724 (0.14%)  3
Fluid overload  2  7/724 (0.97%)  12 6/724 (0.83%)  6
Gout  2  5/724 (0.69%)  6 6/724 (0.83%)  7
Hypercalcaemia  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Hyperglycaemia  2  7/724 (0.97%)  10 16/724 (2.21%)  16
Hyperglycaemic hyperosmolar no  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Hyperkalaemia  2  39/724 (5.39%)  45 16/724 (2.21%)  16
Hypermagnesaemia  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Hypoglycaemia  2  19/724 (2.62%)  21 20/724 (2.76%)  27
Hypokalaemia  2  0/724 (0.00%)  0 2/724 (0.28%)  2
Hyponatraemia  2  3/724 (0.41%)  3 5/724 (0.69%)  6
Hypovolaemia  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Metabolic acidosis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Obesity  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Musculoskeletal and connective tissue disorders     
Arthritis  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Back pain  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Foot deformity  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Intervertebral disc degenerati  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Intervertebral disc protrusion  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Muscular weakness  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Musculoskeletal chest pain  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Musculoskeletal pain  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Neck mass  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Osteoarthritis  2  6/724 (0.83%)  6 3/724 (0.41%)  3
Pain in extremity  2  1/724 (0.14%)  1 3/724 (0.41%)  4
Rhabdomyolysis  2  1/724 (0.14%)  1 4/724 (0.55%)  4
Rheumatoid arthritis  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Rotator cuff syndrome  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Spinal column stenosis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Systemic lupus erythematosus  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute promyelocytic leukaemia  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Adenocarcinoma  2  1/724 (0.14%)  1 2/724 (0.28%)  2
B-cell lymphoma  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Bladder cancer  2  0/724 (0.00%)  0 3/724 (0.41%)  8
Bladder neoplasm  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Bone neoplasm malignant  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Brain neoplasm malignant  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Breast cancer in situ  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Bronchioloalveolar carcinoma  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Burkitt's lymphoma  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Colon cancer  2  3/724 (0.41%)  3 3/724 (0.41%)  6
Colon cancer metastatic  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Hepatic neoplasm malignant  2  2/724 (0.28%)  8 0/724 (0.00%)  0
Lip and/or oral cavity cancer  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Lung adenocarcinoma  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Lung adenocarcinoma metastatic  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Lung cancer metastatic  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Lung neoplasm malignant  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Lung squamous cell carcinoma s  2  0/724 (0.00%)  0 2/724 (0.28%)  4
Lymphoma  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Malignant ascites  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Metastases to bone  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Metastatic neoplasm  2  2/724 (0.28%)  3 0/724 (0.00%)  0
Multiple myeloma  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Nasopharyngeal cancer stage IV  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Neoplasm  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Neoplasm prostate  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Neuroendocrine carcinoma of th  2  1/724 (0.14%)  2 0/724 (0.00%)  0
Non-small cell lung cancer  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Oesophageal carcinoma  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pancreatic carcinoma  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Pancreatic carcinoma metastati  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Prostate cancer  2  1/724 (0.14%)  1 2/724 (0.28%)  2
Renal cancer metastatic  2  1/724 (0.14%)  2 0/724 (0.00%)  0
Renal cell carcinoma  2  3/724 (0.41%)  5 0/724 (0.00%)  0
Salivary gland cancer  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Salivary gland neoplasm  2  1/724 (0.14%)  2 0/724 (0.00%)  0
Sarcoma  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Small cell lung cancer stage u  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Tonsil cancer  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Transitional cell carcinoma  2  1/724 (0.14%)  3 0/724 (0.00%)  0
Nervous system disorders     
Altered state of consciousness  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Amnesia  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Autonomic nervous system imbal  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Brain stem infarction  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Carotid artery disease  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Carotid artery stenosis  2  2/724 (0.28%)  3 4/724 (0.55%)  4
Central nervous system mass  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Cerebellar artery thrombosis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Cerebral infarction  2  3/724 (0.41%)  3 1/724 (0.14%)  1
Cerebral ischaemia  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Cerebral ventricle dilatation  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Cerebrovascular accident  2  12/724 (1.66%)  12 10/724 (1.38%)  12
Cognitive disorder  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Convulsion  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Dizziness  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Dizziness postural  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Dysarthria  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Encephalopathy  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Facial paresis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Grand mal convulsion  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Haemorrhage intracranial  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Headache  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Hepatic encephalopathy  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Hypersomnia  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Hypoaesthesia  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Hypoglycaemic seizure  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Hypoglycaemic unconsciousness  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Intracranial aneurysm  2  1/724 (0.14%)  3 1/724 (0.14%)  1
Ischaemic cerebral infarction  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Ischaemic stroke  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Lacunar infarction  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Loss of consciousness  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Metabolic encephalopathy  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Nerve root compression  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Neuritis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Parkinson's disease  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Polyneuropathy  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Presyncope  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Radiculopathy  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Sciatica  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Spondylitic myelopathy  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Syncope  2  10/724 (1.38%)  10 9/724 (1.24%)  10
Thalamic infarction  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Toxic encephalopathy  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Transient ischaemic attack  2  5/724 (0.69%)  5 10/724 (1.38%)  12
Tremor  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Psychiatric disorders     
Adjustment disorder  2  0/724 (0.00%)  0 2/724 (0.28%)  2
Alcohol abuse  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Alcoholism  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Anxiety  2  0/724 (0.00%)  0 2/724 (0.28%)  2
Delirium  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Depression  2  1/724 (0.14%)  1 2/724 (0.28%)  2
Drug abuse  2  4/724 (0.55%)  4 1/724 (0.14%)  1
Major depression  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Mania  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Mental status changes  2  5/724 (0.69%)  5 6/724 (0.83%)  6
Psychotic disorder  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Suicidal ideation  2  9/724 (1.24%)  10 2/724 (0.28%)  2
Suicide attempt  2  0/724 (0.00%)  0 2/724 (0.28%)  3
Renal and urinary disorders     
Azotaemia  2  0/724 (0.00%)  0 2/724 (0.28%)  2
Bladder mass  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Calculus ureteric  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Calculus urinary  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Diabetic end stage renal disea  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Haematuria  2  2/724 (0.28%)  3 2/724 (0.28%)  4
Hydronephrosis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Nephrolithiasis  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Nephropathy toxic  2  1/724 (0.14%)  1 2/724 (0.28%)  2
Nephrotic syndrome  2  0/724 (0.00%)  0 3/724 (0.41%)  3
Obstructive uropathy  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Polyuria  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Renal disorder  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Renal failure  2  3/724 (0.41%)  3 5/724 (0.69%)  6
Renal failure acute  2  130/724 (17.96%)  190 80/724 (11.05%)  105
Renal failure chronic  2  4/724 (0.55%)  5 7/724 (0.97%)  7
Renal impairment  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Renal mass  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Renal tubular necrosis  2  2/724 (0.28%)  2 3/724 (0.41%)  3
Tubulointerstitial nephritis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Urinary retention  2  1/724 (0.14%)  1 3/724 (0.41%)  3
Reproductive system and breast disorders     
Benign prostatic hyperplasia  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Erectile dysfunction  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Prostatitis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  2  4/724 (0.55%)  4 4/724 (0.55%)  4
Asthma  2  0/724 (0.00%)  0 2/724 (0.28%)  2
Atelectasis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Bronchial hyperreactivity  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Bronchospasm  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Chronic obstructive pulmonary  2  14/724 (1.93%)  20 22/724 (3.04%)  39
Cough  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Dyspnoea  2  2/724 (0.28%)  2 7/724 (0.97%)  9
Dyspnoea exertional  2  0/724 (0.00%)  0 3/724 (0.41%)  3
Epistaxis  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Haemoptysis  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Hypoventilation  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Hypoxia  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Interstitial lung disease  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Lung disorder  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Obstructive airways disorder  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Oropharyngeal pain  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Pleural disorder  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pleural effusion  2  10/724 (1.38%)  13 4/724 (0.55%)  5
Pleurisy  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Pleuritic pain  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pneumonia aspiration  2  3/724 (0.41%)  3 0/724 (0.00%)  0
Pneumonitis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pneumothorax  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pulmonary congestion  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Pulmonary embolism  2  2/724 (0.28%)  2 4/724 (0.55%)  4
Pulmonary fibrosis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pulmonary haemorrhage  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Pulmonary mass  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Pulmonary oedema  2  5/724 (0.69%)  5 8/724 (1.10%)  8
Respiratory arrest  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Respiratory failure  2  5/724 (0.69%)  6 6/724 (0.83%)  7
Sleep apnoea syndrome  2  1/724 (0.14%)  1 2/724 (0.28%)  2
Skin and subcutaneous tissue disorders     
Diabetic foot  2  7/724 (0.97%)  8 10/724 (1.38%)  12
Diabetic ulcer  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Dry gangrene  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Skin ulcer  2  2/724 (0.28%)  3 5/724 (0.69%)  5
Stasis dermatitis  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Social circumstances     
Treatment noncompliance  2  5/724 (0.69%)  5 4/724 (0.55%)  4
Surgical and medical procedures     
Amputation  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Appendicectomy  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Arteriovenous fistula operatio  2  2/724 (0.28%)  2 1/724 (0.14%)  3
Arthrotomy  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Brachytherapy  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Carotid endarterectomy  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Chemotherapy  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Coronary arterial stent insert  2  1/724 (0.14%)  1 4/724 (0.55%)  4
Coronary artery bypass  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Drug rehabilitation  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Elective surgery  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Ethmoid sinus surgery  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Extubation  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Foot amputation  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Gastric banding  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Gastric bypass  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Gastrointestinal tube insertio  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Haemodialysis  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Hip arthroplasty  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Knee arthroplasty  2  0/724 (0.00%)  0 2/724 (0.28%)  2
Leg amputation  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Penile prosthesis insertion  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Rehabilitation therapy  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Therapy regimen changed  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Toe amputation  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Tooth extraction  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Vascular disorders     
Accelerated hypertension  2  2/724 (0.28%)  2 0/724 (0.00%)  0
Aneurysm  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Angiodysplasia  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Aortic aneurysm  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Aortic aneurysm rupture  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Aortic arteriosclerosis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Aortic stenosis  2  2/724 (0.28%)  2 1/724 (0.14%)  1
Arteriosclerosis  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Arteriovenous fistula  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Deep vein thrombosis  2  3/724 (0.41%)  3 0/724 (0.00%)  0
Embolism  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Femoral arterial stenosis  2  2/724 (0.28%)  3 2/724 (0.28%)  2
Haematoma  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Haemorrhage  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Hypertension  2  4/724 (0.55%)  5 6/724 (0.83%)  6
Hypertensive crisis  2  4/724 (0.55%)  4 4/724 (0.55%)  4
Hypertensive emergency  2  3/724 (0.41%)  3 3/724 (0.41%)  4
Hypotension  2  11/724 (1.52%)  13 8/724 (1.10%)  8
Iliac artery stenosis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Intermittent claudication  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Lymphoedema  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Orthostatic hypotension  2  1/724 (0.14%)  3 6/724 (0.83%)  6
Peripheral arterial occlusive  2  1/724 (0.14%)  1 1/724 (0.14%)  1
Peripheral artery aneurysm  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Peripheral embolism  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Peripheral ischaemia  2  3/724 (0.41%)  3 0/724 (0.00%)  0
Peripheral vascular disorder  2  4/724 (0.55%)  6 3/724 (0.41%)  3
Shock  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Shock haemorrhagic  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Thrombosed varicose vein  2  1/724 (0.14%)  1 0/724 (0.00%)  0
Thrombosis  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Vascular occlusion  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Venous insufficiency  2  0/724 (0.00%)  0 1/724 (0.14%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
2
Term from vocabulary, MedDRA 15.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Combination of ARB and ACEI Monotherapy ARB
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/724 (0.00%)      0/724 (0.00%)    
In October, 2012 the DMC recommended that study treatment be stopped primarily because of safety concerns along with low conditional power to detect a treatment effect on the primary outcome.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: Linda Fried, MD, MPH
Organization: VA Pittsburgh Healthcare System and University of Pittsburgh School of Medicine, Pittsburgh, PA
Phone: 412-360-3930
EMail: Linda.Fried@va.gov
Layout table for additonal information
Responsible Party: VA Office of Research and Development ( US Department of Veterans Affairs )
ClinicalTrials.gov Identifier: NCT00555217    
Other Study ID Numbers: 565
First Submitted: November 7, 2007
First Posted: November 8, 2007
Results First Submitted: April 17, 2015
Results First Posted: May 29, 2015
Last Update Posted: May 29, 2015