EMERALD 1: Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis

• Sponsor: Affymax (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00597753
• Collaborator: Takeda (Industry)
• Enrollment: 803
• Locations: 89
• Arms: 2
• Duration (Months): 28
• Patients Per Site: 9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of the study was to evaluate the safety and efficacy of peginesatide in the maintenance treatment of anemia in participants on dialysis.

Condition or Disease	Intervention/Treatment	Phase
Chronic Renal Failure; Chronic Kidney Disease; Anemia	Drug: peginesatide; Drug: Epoetin Alfa	Phase 3

Detailed Description

Anemia associated with chronic kidney disease is due to several factors, primarily the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin. Ancillary factors include the shortened lifespan of red blood cells, iron and other nutritional deficiencies, infection, and inflammation. The presence and severity of anemia are related to the duration and extent of kidney failure. Anemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function, and increased left ventricular hypertrophy and heart failure.

Erythropoiesis stimulating agents (ESAs) have been established as a treatment for anemia in chronic renal failure subjects, and have improved the management of anemia over alternatives such as transfusion. Peginesatide is a parenteral formulation developed for the treatment of anemia in patients with chronic kidney disease. Peginesatide binds to and activates the human erythropoietin receptor, and stimulates erythropoiesis in human red cell precursors in a manner similar to other known erythropoiesis-stimulating agents.

Eligible participants were randomized in a 2:1 ratio to peginesatide administered once every 4 weeks or to continued treatment with epoetin alfa administered 1-3 times each week, respectively. Total commitment time for this study was 4 weeks of screening followed by a minimum of 52 weeks of study treatment.

To evaluate the cardiovascular safety of peginesatide, a cardiovascular composite safety endpoint (CSE) was defined for use in prospectively planned analyses which combined cardiovascular safety data from the four Phase 3 peginesatide studies (NCT00598273, NCT00597753, NCT00598442, and NCT00597584). The CSE consisted of six events: death, stroke, myocardial infarction, and serious adverse events of congestive heart failure, unstable angina, and arrhythmia. An independent Event Review Committee (ERC) was used to provide blinded adjudication of potential CSE events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 803 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: AFX01-12: A Phase 3, Randomized, Active-controlled, Open-label, Multi-center Study of the Safety and Efficacy of Peginesatide for the Maintenance Treatment of Anemia in Hemodialysis Patients Previously Treated With Epoetin Alfa
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Peginesatide	Drug: peginesatide; Participants received peginesatide by intravenous injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa dose. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 grams per deciliter (g/dL) and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.; Other Names: Omontys Hematide AF37702 Injection
Active Comparator: Epoetin alfa	Drug: Epoetin Alfa; Participants continued to receive commercially available epoetin alfa by intravenous injection, at the same starting dose and frequency as received during the last week of the Screening Period, with the first study dose of epoetin alfa administered after randomization at Week 0. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.; Other Names: Epogen

Outcome Measures

Primary Outcome Measures

1. Mean Change in Hemoglobin Between Baseline and the Evaluation Period [Baseline and Weeks 29-36]

   The baseline hemoglobin value is defined as the mean of five hemoglobin values: the four most recent hemoglobin values taken prior to the day of randomization and the value obtained on the day of randomization. The mean hemoglobin during the Evaluation Period for each participant is calculated as the mean of the available hemoglobin values during study Weeks 29 through 36.

Secondary Outcome Measures

1. Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods [Weeks 0 to 36]

2. Proportion of Participants Whose Mean Hemoglobin Level During the Evaluation Period is Within the Target Range of 10.0 - 12.0 Grams Per Deciliter (g/dL) [Weeks 29 to 36]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Participants with chronic renal failure on hemodialysis for ≥ 3 months prior to randomization.

2. On intravenous epoetin alfa maintenance therapy continuously prescribed for a minimum of 8 weeks prior to randomization.

3. Four consecutive hemoglobin values with a mean ≥ 10.0 and ≤ 12.0 g/dL during the screening period

Exclusion Criteria

1. Females who are pregnant or breast-feeding.

2. Known intolerance to any erythropoiesis stimulating agent (ESA) or pegylated molecule or to all parenteral iron supplementation products.

3. Known bleeding or coagulation disorder.

4. Known hematologic disease or cause of anemia other than renal disease

5. Poorly controlled hypertension

6. Evidence of active malignancy within one year prior to randomization.

7. Temporary (untunneled) dialysis access catheter.

8. A scheduled kidney transplant

9. A scheduled surgery that may be expected to lead to significant blood loss.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Facility	Paragould	Arkansas	United States	72450
2	Research Facility	Fairfield	California	United States	94533
3	Research Facility	Granada Hills	California	United States	91344
4	Research Facility	Los Alamitos	California	United States	90720
5	Research Facility	Los Angeles	California	United States	90022
6	Research Facility	Los Angeles	California	United States	90033
7	Research Facility	Los Angeles	California	United States	90095
8	Research Facility	Lynwood	California	United States	90262
9	Research Facility	Monterey Park	California	United States	91754
10	Research Facility	Mountain View	California	United States	94041
11	Research Facility	Paramount	California	United States	90723
12	Research Facilities (2)	San Diego	California	United States	92123
13	Research Facility	San Dimas	California	United States	91773
14	Research Facility	Whittier	California	United States	90603
15	Research Facility	Denver	Colorado	United States	80230
16	Research Facility	Middlebury	Connecticut	United States	06762
17	Research Facility	Hudson	Florida	United States	34667
18	Research Facility	Ocala	Florida	United States	34471
19	Research Facility	Orlando	Florida	United States	32804
20	Research Facility	Orlando	Florida	United States	32806
21	Research Facility	Pembroke Pines	Florida	United States	33028
22	Research Facility	Augusta	Georgia	United States	30901
23	Research Facility	Augusta	Georgia	United States	30912
24	Research Facility	Decatur	Georgia	United States	30030
25	Research Facility	Marietta	Georgia	United States	30060
26	Research Facility	Honolulu	Hawaii	United States	96817
27	Research Facility	Boise	Idaho	United States	83706
28	Research Facility	Chicago	Illinois	United States	60661
29	Research Facility	Evergreen Park	Illinois	United States	60805
30	Research Facility	Gurnee	Illinois	United States	60031
31	Research Facility	Peoria	Illinois	United States	61603
32	Research Facility	Evansville	Indiana	United States	47714
33	Research Facility	Wichita	Kansas	United States	67214
34	Research Facility	Lexington	Kentucky	United States	40513
35	Research Facility	Baton Rouge	Louisiana	United States	70809
36	Research Facility	Lafayette	Louisiana	United States	70506
37	Research Facility	New Orleans	Louisiana	United States	70112
38	Research Facility	Shreveport	Louisiana	United States	71101
39	Research Facility	Bethesda	Maryland	United States	20817
40	Research Facility	Rockville	Maryland	United States	20852
41	Research Facility	Fall River	Massachusetts	United States	02720
42	Research Facility	Worcester	Massachusetts	United States	01605
43	Research Facility	Dearborn	Michigan	United States	48195
44	Research Facility	Kalamazoo	Michigan	United States	49007
45	Research Facility	Columbus	Mississippi	United States	39705
46	Research Facility	Tupelo	Mississippi	United States	38801
47	Research Facility	St. Louis	Missouri	United States	63110
48	Research Facility	Las Vegas	Nevada	United States	89106
49	Research Facility	Eatontown	New Jersey	United States	07724
50	Research Facility	Bronx	New York	United States	10461
51	Research Facility	Bronx	New York	United States	10467
52	Research Facility	Brooklyn	New York	United States	11212
53	Research Facility	New York	New York	United States	10128
54	Research Facility	Williamsville	New York	United States	14221
55	Research Facility	Yonkers	New York	United States	10710
56	Research Facility	Durham	North Carolina	United States	27704
57	Research Facility	Raleigh	North Carolina	United States	27609
58	Research Facility	Canton	Ohio	United States	44718
59	Research Facility	Cincinnati	Ohio	United States	45267
60	Research Facility	Columbus	Ohio	United States	43210
61	Research Facility	Roseburg	Oregon	United States	97471
62	Research Facility	Allentown	Pennsylvania	United States	18103
63	Research Facility	Philadelphia	Pennsylvania	United States	19106
64	Research Facility	Philadelphia	Pennsylvania	United States	19144
65	Research Facility	Pittsburgh	Pennsylvania	United States	15224
66	Research Facilities (2)	Greenville	South Carolina	United States	29605
67	Research Facility	Sumter	South Carolina	United States	29150
68	Research Facility	Dyersburg	Tennessee	United States	38024
69	Research Facility	Knoxville	Tennessee	United States	37923
70	Research Facility	Nashville	Tennessee	United States	37205
71	Research Facility	Arlington	Texas	United States	76011
72	Research Facility	Fort Worth	Texas	United States	76105
73	Research Facility	Fort Worth	Texas	United States	76106
74	Research Facility	Fort Worth	Texas	United States	76133
75	Research Facility	Grand Prairie	Texas	United States	75050
76	Research Facilities (2)	Houston	Texas	United States	77054
77	Research Facility	Houston	Texas	United States	77091
78	Research Facility	McAllen	Texas	United States	78503
79	Research Facility	San Antonio	Texas	United States	78205
80	Research Facility	San Antonio	Texas	United States	78229
81	Research Facility	Tyler	Texas	United States	75701
82	Research Facility	Alexandria	Virginia	United States	22304
83	Research Facility	Chesapeake	Virginia	United States	23320
84	Research Facility	Fairfax	Virginia	United States	22030
85	Research Facility	Mechanicsville	Virginia	United States	23116
86	Research Facilities (2)	Norfolk	Virginia	United States	23507
87	Research Facility	Morgantown	West Virginia	United States	26506
88	Research Facility	Appleton	Wisconsin	United States	54956
89	Research Facility	Oshkosh	Wisconsin	United States	54904

Sponsors and Collaborators

• Affymax
• Takeda

Investigators

• Study Director: Vice President, Clinical Development, Affymax

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Affymax
• ClinicalTrials.gov Identifier: NCT00597753
• Other Study ID Numbers: AFX01-12
• First Posted: Jan 18, 2008
• Last Update Posted: Feb 12, 2013
• Last Verified: Feb 1, 2013

• Keywords provided by Affymax: anemia; chronic kidney disease; CKD; chronic renal failure; CRF; dialysis; erythropoietin; EPO; erythropoiesis stimulating agent; ESA; Hematide™; hemodialysis; hemoglobin; Hb; Hgb; Omontys; peginesatide; red blood cell; red blood cell production
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Failure, Chronic; Anemia; Epoetin Alfa

Study Results

Participant Flow

Arm/Group Title	Peginesatide	Epoetin Alfa
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa dose. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 grams per deciliter (g/dL) and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.	Participants continued to receive commercially available epoetin alfa by intravenous injection, at the same starting dose and frequency as received during the last week of the Screening Period, with the first study dose of epoetin alfa administered after randomization at Week 0. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.
Period Title: Overall Study
STARTED	532	271
COMPLETED	366	202
NOT COMPLETED	166	69

Baseline Characteristics

Arm/Group Title	Peginesatide	Epoetin Alfa	Total
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa dose. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 grams per deciliter (g/dL) and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.	Participants continued to receive commercially available epoetin alfa by intravenous injection, at the same starting dose and frequency as received during the last week of the Screening Period, with the first study dose of epoetin alfa administered after randomization at Week 0. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.	Total of all reporting groups
Overall Participants	524	269	793
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	370 70.6%	190 70.6%	560 70.6%
>=65 years	154 29.4%	79 29.4%	233 29.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (13.96)	57.5 (13.68)	57.4 (13.86)
Sex: Female, Male (Count of Participants)
Female	231 44.1%	125 46.5%	356 44.9%
Male	293 55.9%	144 53.5%	437 55.1%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Hemoglobin Between Baseline and the Evaluation Period
Description	The baseline hemoglobin value is defined as the mean of five hemoglobin values: the four most recent hemoglobin values taken prior to the day of randomization and the value obtained on the day of randomization. The mean hemoglobin during the Evaluation Period for each participant is calculated as the mean of the available hemoglobin values during study Weeks 29 through 36.
Time Frame	Baseline and Weeks 29-36

Outcome Measure Data

Analysis Population Description

Full Analysis Population: All randomized participants who received at least one dose of study medication

Arm/Group Title	Peginesatide	Epoetin Alfa
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa dose. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 grams per deciliter (g/dL) and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.	Participants continued to receive commercially available epoetin alfa by intravenous injection, at the same starting dose and frequency as received during the last week of the Screening Period, with the first study dose of epoetin alfa administered after randomization at Week 0. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.
Measure Participants	524	269
Baseline [N=524, 269]	11.30 (0.523)	11.32 (0.493)
Evaluation Period [N=445, 248]	11.06 (0.932)	11.25 (0.846)
Change from Baseline [N=445, 248]	-0.24 (0.956)	-0.09 (0.922)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide, Epoetin Alfa
	Comments	The sample size for this study was determined based on a two group evaluation of non-inferiority using the t-distribution (one-sided significance level 0.025) with a non inferiority margin of -1.0 g/dL. A sample size of approximately 750 (peginesatide group of 500 and epoetin alfa group of 250) provided at least 99% power for the evaluation of non-inferiority, assuming an expected treatment difference of 0.0 g/dL and a standard deviation of 1.5 g/dL.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A non-inferiority margin of -1.0 g/dL was used in the primary efficacy assessments. Non-inferiority was established if the lower limit of the two-sided 95% confidence interval for the difference between the means of the primary endpoint (peginesatide minus control ESA) was ≥ -1.0 g/dL.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.30 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.072
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods
Time Frame	Weeks 0 to 36

Outcome Measure Data

Analysis Population Description

Full Analysis Population: All randomized participants who received at least one dose of study medication

Arm/Group Title	Peginesatide	Epoetin Alfa
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa dose. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 grams per deciliter (g/dL) and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.	Participants continued to receive commercially available epoetin alfa by intravenous injection, at the same starting dose and frequency as received during the last week of the Screening Period, with the first study dose of epoetin alfa administered after randomization at Week 0. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.
Measure Participants	524	269
Number [percentage of participants]	0.103 0%	0.086 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide, Epoetin Alfa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Proportion of Participants Whose Mean Hemoglobin Level During the Evaluation Period is Within the Target Range of 10.0 - 12.0 Grams Per Deciliter (g/dL)
Time Frame	Weeks 29 to 36

Outcome Measure Data

Analysis Population Description

Full Analysis Population: All randomized participants who received at least one dose of study medication

Arm/Group Title	Peginesatide	Epoetin Alfa
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa dose. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 grams per deciliter (g/dL) and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.	Participants continued to receive commercially available epoetin alfa by intravenous injection, at the same starting dose and frequency as received during the last week of the Screening Period, with the first study dose of epoetin alfa administered after randomization at Week 0. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.
Measure Participants	524	269
Number [percentage of participants]	0.630 0.1%	0.717 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide, Epoetin Alfa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.79 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Peginesatide		Epoetin Alfa
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa dose. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 grams per deciliter (g/dL) and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.		Participants continued to receive commercially available epoetin alfa by intravenous injection, at the same starting dose and frequency as received during the last week of the Screening Period, with the first study dose of epoetin alfa administered after randomization at Week 0. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.
All Cause Mortality
	Peginesatide		Epoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Peginesatide		Epoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	304/524 (58%)		168/269 (62.5%)
Blood and lymphatic system disorders
Anaemia	6/524 (1.1%)		3/269 (1.1%)
Thrombocytopenia	3/524 (0.6%)		0/269 (0%)
Leukocytosis	0/524 (0%)		2/269 (0.7%)
B-lymphocyte abnormalities	1/524 (0.2%)		0/269 (0%)
Coagulopathy	1/524 (0.2%)		0/269 (0%)
Splenic infarction	1/524 (0.2%)		0/269 (0%)
Cardiac disorders
Cardiac failure congestive	37/524 (7.1%)		20/269 (7.4%)
Acute myocardial infarction	19/524 (3.6%)		9/269 (3.3%)
Myocardial infarction	13/524 (2.5%)		9/269 (3.3%)
Atrial fibrillation	15/524 (2.9%)		6/269 (2.2%)
Cardiac arrest	16/524 (3.1%)		5/269 (1.9%)
Coronary artery disease	16/524 (3.1%)		5/269 (1.9%)
Angina pectoris	12/524 (2.3%)		7/269 (2.6%)
Cardio-respiratory arrest	11/524 (2.1%)		4/269 (1.5%)
Atrial flutter	4/524 (0.8%)		3/269 (1.1%)
Bradycardia	5/524 (1%)		2/269 (0.7%)
Acute coronary syndrome	3/524 (0.6%)		3/269 (1.1%)
Angina unstable	2/524 (0.4%)		2/269 (0.7%)
Cardiomyopathy	4/524 (0.8%)		0/269 (0%)
Ischaemic cardiomyopathy	3/524 (0.6%)		1/269 (0.4%)
Myocardial ischaemia	3/524 (0.6%)		1/269 (0.4%)
Ventricular tachycardia	2/524 (0.4%)		2/269 (0.7%)
Ventricular fibrillation	3/524 (0.6%)		0/269 (0%)
Arrhythmia	1/524 (0.2%)		1/269 (0.4%)
Atrioventricular block complete	1/524 (0.2%)		1/269 (0.4%)
Cardiac failure	1/524 (0.2%)		1/269 (0.4%)
Coronary artery stenosis	1/524 (0.2%)		1/269 (0.4%)
Pericardial effusion	1/524 (0.2%)		1/269 (0.4%)
Supraventricular tachycardia	2/524 (0.4%)		0/269 (0%)
Aortic valve stenosis	1/524 (0.2%)		0/269 (0%)
Arteriosclerosis coronary artery	1/524 (0.2%)		0/269 (0%)
Atrioventricular block second degree	1/524 (0.2%)		0/269 (0%)
Bradyarrhythmia	1/524 (0.2%)		0/269 (0%)
Cor pulmonale	1/524 (0.2%)		0/269 (0%)
Coronary artery occlusion	0/524 (0%)		1/269 (0.4%)
Cyanosis	0/524 (0%)		1/269 (0.4%)
Electromechanical dissociation	1/524 (0.2%)		0/269 (0%)
Hypertensive cardiomyopathy	0/524 (0%)		1/269 (0.4%)
Hypertensive heart disease	0/524 (0%)		1/269 (0.4%)
Left ventricular dysfunction	1/524 (0.2%)		0/269 (0%)
Mitral valve incompetence	0/524 (0%)		1/269 (0.4%)
Mitral valve stenosis	1/524 (0.2%)		0/269 (0%)
Palpitations	1/524 (0.2%)		0/269 (0%)
Pericarditis	1/524 (0.2%)		0/269 (0%)
Pericarditis uraemic	1/524 (0.2%)		0/269 (0%)
Sinus bradycardia	0/524 (0%)		1/269 (0.4%)
Tachycardia	1/524 (0.2%)		0/269 (0%)
Ventricular arrhythmia	1/524 (0.2%)		0/269 (0%)
Congenital, familial and genetic disorders
Gastrointestinal arteriovenous malformation	0/524 (0%)		1/269 (0.4%)
Tuberous sclerosis	1/524 (0.2%)		0/269 (0%)
Ear and labyrinth disorders
Vertigo positional	1/524 (0.2%)		0/269 (0%)
Endocrine disorders
Hyperparathyroidism	2/524 (0.4%)		0/269 (0%)
Hyperparathyroidism secondary	0/524 (0%)		1/269 (0.4%)
Hyperparathyroidism tertiary	0/524 (0%)		1/269 (0.4%)
Eye disorders
Retinal detachment	1/524 (0.2%)		0/269 (0%)
Vision blurred	1/524 (0.2%)		0/269 (0%)
Vitreous haemorrhage	1/524 (0.2%)		0/269 (0%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	9/524 (1.7%)		5/269 (1.9%)
Pancreatitis	6/524 (1.1%)		3/269 (1.1%)
Abdominal pain	4/524 (0.8%)		4/269 (1.5%)
Diarrhoea	5/524 (1%)		3/269 (1.1%)
Upper gastrointestinal haemorrhage	4/524 (0.8%)		3/269 (1.1%)
Ascites	3/524 (0.6%)		3/269 (1.1%)
Diabetic gastroparesis	3/524 (0.6%)		2/269 (0.7%)
Gastritis	2/524 (0.4%)		3/269 (1.1%)
Colitis	2/524 (0.4%)		2/269 (0.7%)
Pancreatitis acute	3/524 (0.6%)		1/269 (0.4%)
Mallory-Weiss syndrome	3/524 (0.6%)		0/269 (0%)
Small intestinal obstruction	3/524 (0.6%)		0/269 (0%)
Vomiting	1/524 (0.2%)		2/269 (0.7%)
Colitis ischaemic	2/524 (0.4%)		0/269 (0%)
Colonic polyp	0/524 (0%)		2/269 (0.7%)
Constipation	0/524 (0%)		2/269 (0.7%)
Diverticulum	1/524 (0.2%)		1/269 (0.4%)
Erosive oesophagitis	2/524 (0.4%)		0/269 (0%)
Gastrooesophageal reflux disease	1/524 (0.2%)		1/269 (0.4%)
Haematemesis	1/524 (0.2%)		1/269 (0.4%)
Ileus	2/524 (0.4%)		0/269 (0%)
Intestinal ischaemia	2/524 (0.4%)		0/269 (0%)
Lower gastrointestinal haemorrhage	0/524 (0%)		2/269 (0.7%)
Oesophagitis	2/524 (0.4%)		0/269 (0%)
Abdominal pain lower	1/524 (0.2%)		0/269 (0%)
Anal fissure	0/524 (0%)		1/269 (0.4%)
Duodenitis	1/524 (0.2%)		0/269 (0%)
Gastric ulcer haemorrhage	0/524 (0%)		1/269 (0.4%)
Gastritis hypertrophic	0/524 (0%)		1/269 (0.4%)
Gastroduodenitis	1/524 (0.2%)		0/269 (0%)
Gastrointestinal inflammation	1/524 (0.2%)		0/269 (0%)
Gastrointestinal necrosis	1/524 (0.2%)		0/269 (0%)
Haematochezia	0/524 (0%)		1/269 (0.4%)
Inguinal hernia, obstructive	1/524 (0.2%)		0/269 (0%)
Intestinal haemorrhage	1/524 (0.2%)		0/269 (0%)
Intestinal perforation	1/524 (0.2%)		0/269 (0%)
Intra-abdominal haemorrhage	0/524 (0%)		1/269 (0.4%)
Large intestinal ulcer haemorrhage	0/524 (0%)		1/269 (0.4%)
Nausea	0/524 (0%)		1/269 (0.4%)
Odynophagia	1/524 (0.2%)		0/269 (0%)
Oesophageal disorder	1/524 (0.2%)		0/269 (0%)
Oesophageal dysplasia	1/524 (0.2%)		0/269 (0%)
Oesophageal spasm	1/524 (0.2%)		0/269 (0%)
Oesophageal ulcer	1/524 (0.2%)		0/269 (0%)
Peritonitis	0/524 (0%)		1/269 (0.4%)
Rectal haemorrhage	1/524 (0.2%)		0/269 (0%)
Retroperitoneal haemorrhage	1/524 (0.2%)		0/269 (0%)
Short-bowel syndrome	1/524 (0.2%)		0/269 (0%)
Varices oesophageal	0/524 (0%)		1/269 (0.4%)
General disorders
Non-cardiac chest pain	13/524 (2.5%)		8/269 (3%)
Chest pain	14/524 (2.7%)		4/269 (1.5%)
Asthenia	4/524 (0.8%)		5/269 (1.9%)
Pyrexia	5/524 (1%)		2/269 (0.7%)
Catheter related complication	2/524 (0.4%)		2/269 (0.7%)
Multi-organ failure	2/524 (0.4%)		1/269 (0.4%)
Oedema peripheral	2/524 (0.4%)		0/269 (0%)
Adverse drug reaction	0/524 (0%)		1/269 (0.4%)
Catheter site haemorrhage	0/524 (0%)		1/269 (0.4%)
Catheter thrombosis	1/524 (0.2%)		0/269 (0%)
Chills	1/524 (0.2%)		0/269 (0%)
Death	0/524 (0%)		1/269 (0.4%)
Drug withdrawal syndrome	1/524 (0.2%)		0/269 (0%)
Fatigue	0/524 (0%)		1/269 (0.4%)
Local swelling	0/524 (0%)		1/269 (0.4%)
Pain	0/524 (0%)		1/269 (0.4%)
Sudden cardiac death	1/524 (0.2%)		0/269 (0%)
Systemic inflammatory response syndrome	0/524 (0%)		1/269 (0.4%)
Hepatobiliary disorders
Cholelithiasis	4/524 (0.8%)		1/269 (0.4%)
Cholecystitis acute	4/524 (0.8%)		0/269 (0%)
Cholecystitis	1/524 (0.2%)		2/269 (0.7%)
Hepatic cirrhosis	0/524 (0%)		2/269 (0.7%)
Biliary colic	1/524 (0.2%)		0/269 (0%)
Gallbladder disorder	0/524 (0%)		1/269 (0.4%)
Hepatic congestion	1/524 (0.2%)		0/269 (0%)
Hepatic failure	0/524 (0%)		1/269 (0.4%)
Hepatic mass	0/524 (0%)		1/269 (0.4%)
Hepatic steatosis	0/524 (0%)		1/269 (0.4%)
Jaundice	0/524 (0%)		1/269 (0.4%)
Immune system disorders
Anaphylactic reaction	1/524 (0.2%)		0/269 (0%)
Iodine allergy	1/524 (0.2%)		0/269 (0%)
Infections and infestations
Pneumonia	37/524 (7.1%)		19/269 (7.1%)
Sepsis	15/524 (2.9%)		13/269 (4.8%)
Cellulitis	15/524 (2.9%)		10/269 (3.7%)
Gangrene	8/524 (1.5%)		5/269 (1.9%)
Gastroenteritis	8/524 (1.5%)		5/269 (1.9%)
Staphylococcal bacteraemia	6/524 (1.1%)		7/269 (2.6%)
Urinary tract infection	11/524 (2.1%)		2/269 (0.7%)
Bacteraemia	5/524 (1%)		5/269 (1.9%)
Lobar pneumonia	5/524 (1%)		5/269 (1.9%)
Septic shock	6/524 (1.1%)		4/269 (1.5%)
Arteriovenous graft site infection	2/524 (0.4%)		7/269 (2.6%)
Osteomyelitis	4/524 (0.8%)		5/269 (1.9%)
Staphylococcal sepsis	5/524 (1%)		3/269 (1.1%)
Catheter sepsis	2/524 (0.4%)		5/269 (1.9%)
Bronchitis	4/524 (0.8%)		2/269 (0.7%)
Catheter related infection	2/524 (0.4%)		3/269 (1.1%)
Clostridium difficile colitis	3/524 (0.6%)		2/269 (0.7%)
Staphylococcal infection	3/524 (0.6%)		2/269 (0.7%)
Diverticulitis	2/524 (0.4%)		2/269 (0.7%)
Upper respiratory tract infection	2/524 (0.4%)		2/269 (0.7%)
Abscess limb	1/524 (0.2%)		2/269 (0.7%)
Arteriovenous fistula site infection	0/524 (0%)		3/269 (1.1%)
Diabetic foot infection	2/524 (0.4%)		1/269 (0.4%)
Gastroenteritis viral	1/524 (0.2%)		2/269 (0.7%)
Localised infection	2/524 (0.4%)		1/269 (0.4%)
Oesophageal candidiasis	2/524 (0.4%)		1/269 (0.4%)
Appendicitis	2/524 (0.4%)		0/269 (0%)
Arthritis bacterial	1/524 (0.2%)		1/269 (0.4%)
Bacterial sepsis	1/524 (0.2%)		1/269 (0.4%)
Catheter bacteraemia	2/524 (0.4%)		0/269 (0%)
Device related infection	1/524 (0.2%)		1/269 (0.4%)
Enterocolitis infectious	2/524 (0.4%)		0/269 (0%)
Haematoma infection	2/524 (0.4%)		0/269 (0%)
Influenza	1/524 (0.2%)		1/269 (0.4%)
Streptococcal bacteraemia	2/524 (0.4%)		0/269 (0%)
Urosepsis	2/524 (0.4%)		0/269 (0%)
Abdominal wall abscess	1/524 (0.2%)		0/269 (0%)
Abscess	1/524 (0.2%)		0/269 (0%)
Abscess neck	1/524 (0.2%)		0/269 (0%)
Arteriosclerotic gangrene	0/524 (0%)		1/269 (0.4%)
Arteriovenous graft site abscess	1/524 (0.2%)		0/269 (0%)
Arthritis infective	1/524 (0.2%)		0/269 (0%)
Bacterial disease carrier	1/524 (0.2%)		0/269 (0%)
Bronchitis pneumococcal	1/524 (0.2%)		0/269 (0%)
Bronchitis viral	0/524 (0%)		1/269 (0.4%)
Campylobacter intestinal infection	1/524 (0.2%)		0/269 (0%)
Candida sepsis	0/524 (0%)		1/269 (0.4%)
Central line infection	1/524 (0.2%)		0/269 (0%)
Chest wall abscess	0/524 (0%)		1/269 (0.4%)
Clostridial infection	0/524 (0%)		1/269 (0.4%)
Emphysematous cystitis	1/524 (0.2%)		0/269 (0%)
Empyema	0/524 (0%)		1/269 (0.4%)
Endocarditis	1/524 (0.2%)		0/269 (0%)
Enterococcal sepsis	1/524 (0.2%)		0/269 (0%)
Escherichia urinary tract infection	1/524 (0.2%)		0/269 (0%)
Genital abscess	0/524 (0%)		1/269 (0.4%)
Groin abscess	1/524 (0.2%)		0/269 (0%)
Herpes zoster	0/524 (0%)		1/269 (0.4%)
Intervertebral discitis	1/524 (0.2%)		0/269 (0%)
Klebsiella bacteraemia	1/524 (0.2%)		0/269 (0%)
Lung infection	1/524 (0.2%)		0/269 (0%)
Necrotising fasciitis	1/524 (0.2%)		0/269 (0%)
Neurosyphilis	1/524 (0.2%)		0/269 (0%)
Osteomyelitis chronic	1/524 (0.2%)		0/269 (0%)
Paronychia	1/524 (0.2%)		0/269 (0%)
Pelvic abscess	1/524 (0.2%)		0/269 (0%)
Pleural infection bacterial	0/524 (0%)		1/269 (0.4%)
Pneumonia bacterial	1/524 (0.2%)		0/269 (0%)
Pneumonia pneumococcal	0/524 (0%)		1/269 (0.4%)
Pneumonia primary atypical	1/524 (0.2%)		0/269 (0%)
Pneumonia staphylococcal	0/524 (0%)		1/269 (0.4%)
Post procedural sepsis	0/524 (0%)		1/269 (0.4%)
Postoperative wound infection	1/524 (0.2%)		0/269 (0%)
Pseudomonal bacteraemia	1/524 (0.2%)		0/269 (0%)
Psoas abscess	0/524 (0%)		1/269 (0.4%)
Pyelonephritis	0/524 (0%)		1/269 (0.4%)
Sepsis syndrome	0/524 (0%)		1/269 (0.4%)
Septic embolus	1/524 (0.2%)		0/269 (0%)
Sinusitis	1/524 (0.2%)		0/269 (0%)
Tracheobronchitis	0/524 (0%)		1/269 (0.4%)
Viral infection	0/524 (0%)		1/269 (0.4%)
Viral upper respiratory tract infection	0/524 (0%)		1/269 (0.4%)
Wound infection	0/524 (0%)		1/269 (0.4%)
Wound infection bacterial	0/524 (0%)		1/269 (0.4%)
Injury, poisoning and procedural complications
Arteriovenous graft thrombosis	6/524 (1.1%)		8/269 (3%)
Arteriovenous fistula thrombosis	6/524 (1.1%)		5/269 (1.9%)
Post procedural haemorrhage	6/524 (1.1%)		2/269 (0.7%)
Arteriovenous fistula site haemorrhage	4/524 (0.8%)		2/269 (0.7%)
Femur fracture	3/524 (0.6%)		2/269 (0.7%)
Hip fracture	3/524 (0.6%)		2/269 (0.7%)
Vascular graft complication	1/524 (0.2%)		4/269 (1.5%)
Arteriovenous fistula site complication	1/524 (0.2%)		3/269 (1.1%)
Arteriovenous fistula aneurysm	3/524 (0.6%)		0/269 (0%)
Arteriovenous graft aneurysm	1/524 (0.2%)		2/269 (0.7%)
Fall	2/524 (0.4%)		1/269 (0.4%)
Arteriovenous graft site haemorrhage	0/524 (0%)		2/269 (0.7%)
Femoral neck fracture	1/524 (0.2%)		1/269 (0.4%)
Head injury	0/524 (0%)		2/269 (0.7%)
Lower limb fracture	2/524 (0.4%)		0/269 (0%)
Pelvic fracture	1/524 (0.2%)		1/269 (0.4%)
Post procedural haematoma	2/524 (0.4%)		0/269 (0%)
Procedural hypotension	1/524 (0.2%)		1/269 (0.4%)
Thoracic vertebral fracture	1/524 (0.2%)		1/269 (0.4%)
Back injury	1/524 (0.2%)		0/269 (0%)
Cervical vertebral fracture	0/524 (0%)		1/269 (0.4%)
Contrast media reaction	1/524 (0.2%)		0/269 (0%)
Contusion	1/524 (0.2%)		0/269 (0%)
Drug toxicity	1/524 (0.2%)		0/269 (0%)
Eschar	1/524 (0.2%)		0/269 (0%)
Facial bones fracture	0/524 (0%)		1/269 (0.4%)
Fibula fracture	1/524 (0.2%)		0/269 (0%)
Foot fracture	1/524 (0.2%)		0/269 (0%)
Fractured sacrum	1/524 (0.2%)		0/269 (0%)
Gastrointestinal anastomotic leak	0/524 (0%)		1/269 (0.4%)
Hand fracture	1/524 (0.2%)		0/269 (0%)
Humerus fracture	1/524 (0.2%)		0/269 (0%)
Jaw fracture	1/524 (0.2%)		0/269 (0%)
Open wound	1/524 (0.2%)		0/269 (0%)
Post procedural haematuria	1/524 (0.2%)		0/269 (0%)
Postoperative fever	1/524 (0.2%)		0/269 (0%)
Pubic rami fracture	1/524 (0.2%)		0/269 (0%)
Rib fracture	0/524 (0%)		1/269 (0.4%)
Seroma	1/524 (0.2%)		0/269 (0%)
Skeletal injury	1/524 (0.2%)		0/269 (0%)
Spinal cord injury cervical	1/524 (0.2%)		0/269 (0%)
Spinal fracture	1/524 (0.2%)		0/269 (0%)
Subdural haematoma	0/524 (0%)		1/269 (0.4%)
Subdural haemorrhage	0/524 (0%)		1/269 (0.4%)
Tendon rupture	1/524 (0.2%)		0/269 (0%)
Therapeutic agent toxicity	0/524 (0%)		1/269 (0.4%)
Tibia fracture	1/524 (0.2%)		0/269 (0%)
Vascular graft occlusion	0/524 (0%)		1/269 (0.4%)
Wound	1/524 (0.2%)		0/269 (0%)
Investigations
Occult blood positive	2/524 (0.4%)		0/269 (0%)
Alanine aminotransferase decreased	1/524 (0.2%)		0/269 (0%)
Anticoagulation drug level above therapeutic	1/524 (0.2%)		0/269 (0%)
Blood alkaline phosphatase increased	1/524 (0.2%)		0/269 (0%)
Blood bilirubin increased	1/524 (0.2%)		0/269 (0%)
Blood pressure increased	1/524 (0.2%)		0/269 (0%)
International normalised ratio decreased	1/524 (0.2%)		0/269 (0%)
International normalised ratio increased	1/524 (0.2%)		0/269 (0%)
Oxygen saturation decreased	1/524 (0.2%)		0/269 (0%)
Prothrombin time shortened	1/524 (0.2%)		0/269 (0%)
Sputum culture positive	0/524 (0%)		1/269 (0.4%)
Transaminases increased	1/524 (0.2%)		0/269 (0%)
Troponin increased	1/524 (0.2%)		0/269 (0%)
Metabolism and nutrition disorders
Fluid overload	21/524 (4%)		18/269 (6.7%)
Hyperkalaemia	24/524 (4.6%)		15/269 (5.6%)
Hypoglycaemia	8/524 (1.5%)		7/269 (2.6%)
Hyperglycaemia	7/524 (1.3%)		1/269 (0.4%)
Dehydration	3/524 (0.6%)		3/269 (1.1%)
Diabetic ketoacidosis	3/524 (0.6%)		1/269 (0.4%)
Hypocalcaemia	4/524 (0.8%)		0/269 (0%)
Diabetes mellitus inadequate control	3/524 (0.6%)		0/269 (0%)
Diabetic foot	2/524 (0.4%)		1/269 (0.4%)
Hypercalcaemia	1/524 (0.2%)		2/269 (0.7%)
Hypokalaemia	2/524 (0.4%)		0/269 (0%)
Hyponatraemia	1/524 (0.2%)		1/269 (0.4%)
Metabolic acidosis	2/524 (0.4%)		0/269 (0%)
Anorexia	1/524 (0.2%)		0/269 (0%)
Cachexia	1/524 (0.2%)		0/269 (0%)
Calciphylaxis	0/524 (0%)		1/269 (0.4%)
Diabetes mellitus	0/524 (0%)		1/269 (0.4%)
Failure to thrive	1/524 (0.2%)		0/269 (0%)
Fluid retention	1/524 (0.2%)		0/269 (0%)
Gout	1/524 (0.2%)		0/269 (0%)
Hypoglycaemic unconsciousness	1/524 (0.2%)		0/269 (0%)
Hypomagnesaemia	1/524 (0.2%)		0/269 (0%)
Hypovolaemia	1/524 (0.2%)		0/269 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	3/524 (0.6%)		3/269 (1.1%)
Back pain	0/524 (0%)		2/269 (0.7%)
Cervical spinal stenosis	2/524 (0.4%)		0/269 (0%)
Muscular weakness	1/524 (0.2%)		1/269 (0.4%)
Osteoarthritis	1/524 (0.2%)		1/269 (0.4%)
Pain in extremity	1/524 (0.2%)		1/269 (0.4%)
Spinal column stenosis	1/524 (0.2%)		1/269 (0.4%)
Arthralgia	1/524 (0.2%)		0/269 (0%)
Bursitis	1/524 (0.2%)		0/269 (0%)
Chondrocalcinosis pyrophosphate	0/524 (0%)		1/269 (0.4%)
Connective tissue disorder	0/524 (0%)		1/269 (0.4%)
Fasciitis	1/524 (0.2%)		0/269 (0%)
Flank pain	0/524 (0%)		1/269 (0.4%)
Intervertebral disc degeneration	1/524 (0.2%)		0/269 (0%)
Lumbar spinal stenosis	1/524 (0.2%)		0/269 (0%)
Muscle twitching	1/524 (0.2%)		0/269 (0%)
Musculoskeletal pain	0/524 (0%)		1/269 (0.4%)
Pathological fracture	0/524 (0%)		1/269 (0.4%)
Spinal osteoarthritis	0/524 (0%)		1/269 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma	4/524 (0.8%)		3/269 (1.1%)
Colon adenoma	0/524 (0%)		2/269 (0.7%)
Colon cancer	2/524 (0.4%)		0/269 (0%)
Bile duct cancer	0/524 (0%)		1/269 (0.4%)
Breast cancer	1/524 (0.2%)		0/269 (0%)
Hepatic neoplasm malignant	0/524 (0%)		1/269 (0.4%)
Laryngeal cancer	1/524 (0.2%)		0/269 (0%)
Lung adenocarcinoma metastatic	1/524 (0.2%)		0/269 (0%)
Lung cancer metastatic	1/524 (0.2%)		0/269 (0%)
Lung neoplasm	0/524 (0%)		1/269 (0.4%)
Metastases to lung	0/524 (0%)		1/269 (0.4%)
Neurilemmoma	1/524 (0.2%)		0/269 (0%)
Non-small cell lung cancer	1/524 (0.2%)		0/269 (0%)
Prostate cancer	1/524 (0.2%)		0/269 (0%)
Refractory anaemia	1/524 (0.2%)		0/269 (0%)
Retroperitoneal neoplasm	0/524 (0%)		1/269 (0.4%)
Small cell lung cancer stage unspecified	0/524 (0%)		1/269 (0.4%)
Tongue neoplasm malignant stage unspecified	1/524 (0.2%)		0/269 (0%)
Tonsil cancer	1/524 (0.2%)		0/269 (0%)
Uterine cancer	1/524 (0.2%)		0/269 (0%)
Nervous system disorders
Cerebrovascular accident	8/524 (1.5%)		8/269 (3%)
Syncope	6/524 (1.1%)		8/269 (3%)
Convulsion	12/524 (2.3%)		1/269 (0.4%)
Transient ischaemic attack	5/524 (1%)		5/269 (1.9%)
Presyncope	4/524 (0.8%)		1/269 (0.4%)
Anoxic encephalopathy	3/524 (0.6%)		0/269 (0%)
Headache	3/524 (0.6%)		0/269 (0%)
Subarachnoid haemorrhage	1/524 (0.2%)		2/269 (0.7%)
Aphasia	0/524 (0%)		2/269 (0.7%)
Carotid artery stenosis	1/524 (0.2%)		1/269 (0.4%)
Cerebral infarction	0/524 (0%)		2/269 (0.7%)
Cerebral ischaemia	1/524 (0.2%)		1/269 (0.4%)
Depressed level of consciousness	1/524 (0.2%)		1/269 (0.4%)
Facial palsy	2/524 (0.4%)		0/269 (0%)
Haemorrhagic stroke	1/524 (0.2%)		1/269 (0.4%)
Metabolic encephalopathy	1/524 (0.2%)		1/269 (0.4%)
Altered state of consciousness	1/524 (0.2%)		0/269 (0%)
Cervical myelopathy	1/524 (0.2%)		0/269 (0%)
Cervicobrachial syndrome	1/524 (0.2%)		0/269 (0%)
Complex partial seizures	0/524 (0%)		1/269 (0.4%)
Dementia Alzheimer's type	1/524 (0.2%)		0/269 (0%)
Diabetic autonomic neuropathy	0/524 (0%)		1/269 (0.4%)
Embolic stroke	0/524 (0%)		1/269 (0.4%)
Encephalitis	1/524 (0.2%)		0/269 (0%)
Encephalopathy	1/524 (0.2%)		0/269 (0%)
Haemorrhage intracranial	1/524 (0.2%)		0/269 (0%)
Hypoglycaemic encephalopathy	0/524 (0%)		1/269 (0.4%)
Ischaemic cerebral infarction	1/524 (0.2%)		0/269 (0%)
Ischaemic stroke	1/524 (0.2%)		0/269 (0%)
Lacunar infarction	1/524 (0.2%)		0/269 (0%)
Lethargy	1/524 (0.2%)		0/269 (0%)
Lumbar radiculopathy	1/524 (0.2%)		0/269 (0%)
Myoclonic epilepsy	1/524 (0.2%)		0/269 (0%)
Myoclonus	1/524 (0.2%)		0/269 (0%)
Neuropathy peripheral	1/524 (0.2%)		0/269 (0%)
Reversible ischaemic neurological deficit	1/524 (0.2%)		0/269 (0%)
Spinal cord compression	0/524 (0%)		1/269 (0.4%)
Spinal cord infarction	1/524 (0.2%)		0/269 (0%)
Status epilepticus	1/524 (0.2%)		0/269 (0%)
Thalamus haemorrhage	1/524 (0.2%)		0/269 (0%)
Psychiatric disorders
Mental status changes	8/524 (1.5%)		8/269 (3%)
Delirium	2/524 (0.4%)		2/269 (0.7%)
Bipolar disorder	1/524 (0.2%)		0/269 (0%)
Confusional state	0/524 (0%)		1/269 (0.4%)
Depression suicidal	1/524 (0.2%)		0/269 (0%)
Homicidal ideation	1/524 (0.2%)		0/269 (0%)
Schizophrenia, paranoid type	1/524 (0.2%)		0/269 (0%)
Suicidal ideation	1/524 (0.2%)		0/269 (0%)
Renal and urinary disorders
Renal failure chronic	4/524 (0.8%)		1/269 (0.4%)
Azotaemia	3/524 (0.6%)		1/269 (0.4%)
Bladder perforation	1/524 (0.2%)		0/269 (0%)
Hydronephrosis	1/524 (0.2%)		0/269 (0%)
Nephrosclerosis	0/524 (0%)		1/269 (0.4%)
Obstructive uropathy	1/524 (0.2%)		0/269 (0%)
Renal cyst	1/524 (0.2%)		0/269 (0%)
Renal failure	1/524 (0.2%)		0/269 (0%)
Ureteric dilatation	0/524 (0%)		1/269 (0.4%)
Urinary bladder haemorrhage	1/524 (0.2%)		0/269 (0%)
Reproductive system and breast disorders
Prostatitis	2/524 (0.4%)		0/269 (0%)
Breast calcifications	1/524 (0.2%)		0/269 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	16/524 (3.1%)		5/269 (1.9%)
Pulmonary oedema	15/524 (2.9%)		5/269 (1.9%)
Chronic obstructive pulmonary disease	8/524 (1.5%)		6/269 (2.2%)
Dyspnoea	10/524 (1.9%)		4/269 (1.5%)
Pleural effusion	5/524 (1%)		5/269 (1.9%)
Acute respiratory failure	6/524 (1.1%)		3/269 (1.1%)
Asthma	4/524 (0.8%)		1/269 (0.4%)
Pulmonary hypertension	4/524 (0.8%)		1/269 (0.4%)
Acute pulmonary oedema	2/524 (0.4%)		2/269 (0.7%)
Respiratory distress	2/524 (0.4%)		2/269 (0.7%)
Hypoxia	1/524 (0.2%)		2/269 (0.7%)
Pulmonary embolism	3/524 (0.6%)		0/269 (0%)
Haemoptysis	2/524 (0.4%)		0/269 (0%)
Respiratory arrest	2/524 (0.4%)		0/269 (0%)
Aspiration	1/524 (0.2%)		0/269 (0%)
Bronchospasm	1/524 (0.2%)		0/269 (0%)
Cough	0/524 (0%)		1/269 (0.4%)
Dyspnoea exertional	1/524 (0.2%)		0/269 (0%)
Emphysema	1/524 (0.2%)		0/269 (0%)
Hiccups	1/524 (0.2%)		0/269 (0%)
Laryngeal stenosis	1/524 (0.2%)		0/269 (0%)
Lung infiltration	1/524 (0.2%)		0/269 (0%)
Pneumonia aspiration	0/524 (0%)		1/269 (0.4%)
Pneumonitis	1/524 (0.2%)		0/269 (0%)
Pneumothorax	0/524 (0%)		1/269 (0.4%)
Pulmonary congestion	1/524 (0.2%)		0/269 (0%)
Respiratory acidosis	1/524 (0.2%)		0/269 (0%)
Restrictive pulmonary disease	1/524 (0.2%)		0/269 (0%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/524 (0.2%)		2/269 (0.7%)
Skin ulcer	1/524 (0.2%)		2/269 (0.7%)
Panniculitis	2/524 (0.4%)		0/269 (0%)
Diabetic ulcer	1/524 (0.2%)		0/269 (0%)
Eczema	1/524 (0.2%)		0/269 (0%)
Skin necrosis	1/524 (0.2%)		0/269 (0%)
Vascular disorders
Hypotension	19/524 (3.6%)		7/269 (2.6%)
Hypertension	12/524 (2.3%)		5/269 (1.9%)
Hypertensive crisis	7/524 (1.3%)		7/269 (2.6%)
Peripheral vascular disorder	4/524 (0.8%)		4/269 (1.5%)
Accelerated hypertension	3/524 (0.6%)		1/269 (0.4%)
Peripheral ischaemia	3/524 (0.6%)		1/269 (0.4%)
Steal syndrome	2/524 (0.4%)		2/269 (0.7%)
Deep vein thrombosis	1/524 (0.2%)		2/269 (0.7%)
Vascular pseudoaneurysm	2/524 (0.4%)		1/269 (0.4%)
Arteriosclerosis	1/524 (0.2%)		1/269 (0.4%)
Hypertensive emergency	1/524 (0.2%)		1/269 (0.4%)
Malignant hypertension	2/524 (0.4%)		0/269 (0%)
Peripheral arterial occlusive disease	2/524 (0.4%)		0/269 (0%)
Vena cava thrombosis	2/524 (0.4%)		0/269 (0%)
Arterial disorder	0/524 (0%)		1/269 (0.4%)
Arterial occlusive disease	0/524 (0%)		1/269 (0.4%)
Essential hypertension	1/524 (0.2%)		0/269 (0%)
Femoral arterial stenosis	0/524 (0%)		1/269 (0.4%)
Haematoma	1/524 (0.2%)		0/269 (0%)
Haemorrhage	0/524 (0%)		1/269 (0.4%)
Jugular vein thrombosis	0/524 (0%)		1/269 (0.4%)
Varicose vein	0/524 (0%)		1/269 (0.4%)
Venous stenosis	1/524 (0.2%)		0/269 (0%)
Other (Not Including Serious) Adverse Events
	Peginesatide		Epoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	445/524 (84.9%)		235/269 (87.4%)
Gastrointestinal disorders
Diarrhoea	98/524 (18.7%)		35/269 (13%)
Nausea	89/524 (17%)		51/269 (19%)
Vomiting	86/524 (16.4%)		32/269 (11.9%)
Constipation	37/524 (7.1%)		33/269 (12.3%)
Abdominal pain	31/524 (5.9%)		20/269 (7.4%)
Abdominal pain upper	27/524 (5.2%)		13/269 (4.8%)
Gastrooesophageal reflux disease	17/524 (3.2%)		20/269 (7.4%)
Haemorrhoids	7/524 (1.3%)		14/269 (5.2%)
General disorders
Pyrexia	62/524 (11.8%)		39/269 (14.5%)
Oedema peripheral	45/524 (8.6%)		23/269 (8.6%)
Asthenia	41/524 (7.8%)		16/269 (5.9%)
Fatigue	33/524 (6.3%)		20/269 (7.4%)
Pain	24/524 (4.6%)		15/269 (5.6%)
Chills	20/524 (3.8%)		16/269 (5.9%)
Infections and infestations
Upper respiratory tract infection	61/524 (11.6%)		40/269 (14.9%)
Urinary tract infection	40/524 (7.6%)		26/269 (9.7%)
Nasopharyngitis	37/524 (7.1%)		25/269 (9.3%)
Bronchitis	35/524 (6.7%)		12/269 (4.5%)
Sinusitis	27/524 (5.2%)		13/269 (4.8%)
Injury, poisoning and procedural complications
Arteriovenous fistula site complication	77/524 (14.7%)		43/269 (16%)
Arteriovenous graft thrombosis	42/524 (8%)		24/269 (8.9%)
Vascular graft complication	39/524 (7.4%)		24/269 (8.9%)
Arteriovenous fistula thrombosis	38/524 (7.3%)		15/269 (5.6%)
Fall	38/524 (7.3%)		15/269 (5.6%)
Procedural hypotension	33/524 (6.3%)		23/269 (8.6%)
Arteriovenous fistula site haemorrhage	31/524 (5.9%)		7/269 (2.6%)
Metabolism and nutrition disorders
Hyperkalaemia	32/524 (6.1%)		25/269 (9.3%)
Fluid overload	20/524 (3.8%)		17/269 (6.3%)
Musculoskeletal and connective tissue disorders
Muscle spasms	57/524 (10.9%)		40/269 (14.9%)
Pain in extremity	54/524 (10.3%)		32/269 (11.9%)
Back pain	51/524 (9.7%)		35/269 (13%)
Arthralgia	49/524 (9.4%)		25/269 (9.3%)
Musculoskeletal pain	26/524 (5%)		20/269 (7.4%)
Nervous system disorders
Headache	74/524 (14.1%)		40/269 (14.9%)
Dizziness	55/524 (10.5%)		33/269 (12.3%)
Psychiatric disorders
Insomnia	34/524 (6.5%)		20/269 (7.4%)
Anxiety	31/524 (5.9%)		15/269 (5.6%)
Respiratory, thoracic and mediastinal disorders
Cough	101/524 (19.3%)		52/269 (19.3%)
Dyspnoea	89/524 (17%)		51/269 (19%)
Pharyngolaryngeal pain	23/524 (4.4%)		15/269 (5.6%)
Skin and subcutaneous tissue disorders
Pruritus	27/524 (5.2%)		16/269 (5.9%)
Vascular disorders
Hypotension	49/524 (9.4%)		27/269 (10%)
Hypertension	43/524 (8.2%)		23/269 (8.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first publication of the primary safety and efficacy results will include data from all appropriate study sites. Either after the first multicenter publication, or following 36 months after the completion of the study, Investigators are free to publish; such publications may not contain Sponsor Confidential Information and may be subject to Sponsor review 60 days prior to submission for publication.