EMERALD 2: 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: NCT00597584
• Collaborator: Takeda (Industry)
• Enrollment: 823
• Locations: 84
• Arms: 2
• Duration (Months): 27
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this 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 or Epoetin beta	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 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 injection, a composite safety endpoint (CSE) was defined for use in prospectively planned analyses which combined cardiovascular safety data from the four Phase 3 peginesatide injection 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: 823 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: AFX01-14: 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
• Study Start Date: Oct 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 (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study. 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: Omontys Hematide AF37702 Injection
Active Comparator: Epoetin	Drug: Epoetin alfa or Epoetin beta; Participants continued to receive commercially available epoetin alfa or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta 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 Neorecormon

Outcome Measures

Primary Outcome Measures

1. Mean Change in Hemoglobin Between Baseline and the Evaluation Period [Baseline to 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 IV epoetin alfa or beta 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 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	Phoenix	Arizona	United States	85012
2	Research Facility	Hot Springs	Arkansas	United States	71901
3	Research Facility	McGehee	Arkansas	United States	71654
4	Research Facility	Pine Bluff	Arkansas	United States	71603
5	Research Facility	Bakersfield	California	United States	93309
6	Research Facility	Glendale	California	United States	91205
7	Research Facility	Los Angeles	California	United States	90033
8	Research Facility	Los Angeles	California	United States	90048
9	Research Facility	Los Angeles	California	United States	90073
10	Research Facility	Riverside	California	United States	92505
11	Research Facility	Simi Valley	California	United States	93065
12	Research Facility	Whittier	California	United States	90602
13	Research Facility	Yuba City	California	United States	95991
14	Research Facility	Westminster	Colorado	United States	80031
15	Research Facility	Lauderdale Lakes	Florida	United States	33313
16	Research Facility	Miami	Florida	United States	33173
17	Research Facility	Pinecrest	Florida	United States	33156
18	Research Facility	Flossmoor	Illinois	United States	60422
19	Research Facility	Hines	Illinois	United States	60141
20	Research Facility	Louisville	Kentucky	United States	40202
21	Research Facility	Rockville	Maryland	United States	20850
22	Research Facility	Springfield	Massachusetts	United States	01107
23	Research Facility	Detroit	Michigan	United States	48202
24	Research Facility	Detroit	Michigan	United States	48236
25	Research Facility	Brookhaven	Mississippi	United States	39601
26	Research Facility	Bronx	New York	United States	10461
27	Research Facility	Brooklyn	New York	United States	11238
28	Research Facility	Flushing	New York	United States	11355
29	Research Facility	Asheville	North Carolina	United States	28801
30	Research Facility	Toledo	Ohio	United States	43606
31	Research Facility	Oklahoma City	Oklahoma	United States	73116
32	Research Facility	Erie	Pennsylvania	United States	16507
33	Research Facility	Philadelphia	Pennsylvania	United States	19141
34	Research Facility	Providence	Rhode Island	United States	02904
35	Research Facility	Orangeburg	South Carolina	United States	29118
36	Research Facility	Arlington	Texas	United States	76015
37	Research Facility	Houston	Texas	United States	77099
38	Research Facility	San Antonio	Texas	United States	78215
39	Research Facility	Fairfax	Virginia	United States	22033
40	Research Facility	Burgas		Bulgaria	8000
41	Research Facility	Pazardzhik		Bulgaria	4400
42	Research Facility	Pleven		Bulgaria	5800
43	Research Facility	Plovdiv		Bulgaria	4000
44	Research Facility	Plovdiv		Bulgaria	4003
45	Research Facility	Rousse		Bulgaria	7002
46	Research Facility	Sofia		Bulgaria	1309
47	Research Facilities (2)	Sofia		Bulgaria	1431
48	Research Facility	Sofia		Bulgaria	1527
49	Research Facility	Sofia		Bulgaria	1606
50	Research Facility	Varna		Bulgaria	9010
51	Research Facility	Veliko Tarnovo		Bulgaria	5000
52	Research Facility	Amiens Cedex 1		France	80054
53	Research Facility	Bordeaux		France	33000
54	Research Facility	Montpellier Cedex 5		France	34295
55	Research Facility	Vannes		France	56017
56	Research Facilities (2)	Bremen		Germany	28359
57	Research Facility	Franfurt		Germany	60528
58	Research Facility	Hamburg		Germany	22297
59	Research Facility	Kaiserslautern		Germany	67655
60	Research Facility	Como		Italy	22100
61	Research Facility	Cremona		Italy	26100
62	Research Facility	Lecco		Italy	23900
63	Research Facility	Modena		Italy	41100
64	Research Facility	Prato		Italy	59100
65	Research Facility	Ciechanow		Poland	06-400
66	Research Facility	Katowice		Poland	40-027
67	Research Facility	Pabianice		Poland	95-200
68	Research Facility	Wloclawek		Poland	87-800
69	Research Facility	Bucuresti		Romania	014461
70	Research Facility	Bucuresti		Romania	050098
71	Research Facility	Iasi		Romania	700503
72	Research Facility	Alicante		Spain	03010
73	Research Facility	Barcelona		Spain	08025
74	Research Facility	Barcelona		Spain	08902
75	Research Facility	Barcelona		Spain	08907
76	Research Facility	Ciudad Real		Spain	13005
77	Research Facility	Madrid		Spain	28041
78	Research Facility	Madrid		Spain	28922
79	Research Facility	Santander		Spain	39008
80	Research Facility	Carshalton		United Kingdom	SM5 1AA
81	Research Facility	London		United Kingdom	E1 1BB
82	Research Facility	London		United Kingdom	SE5 9RS
83	Research Facility	London		United Kingdom	SW17 0QT
84	Research Facility	Swansea		United Kingdom	SA6 6NL

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: NCT00597584
• Other Study ID Numbers: AFX01-14; 2007-004153-28
• First Posted: Jan 18, 2008
• Last Update Posted: Mar 8, 2013
• Last Verified: Mar 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
Arm/Group Description	Participants received peginesatide by intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study. 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 or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta 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	549	274
COMPLETED	421	211
NOT COMPLETED	128	63

Baseline Characteristics

Arm/Group Title	Peginesatide	Epoetin	Total
Arm/Group Description	Participants received peginesatide by intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study. 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 or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta 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	542	273	815
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	350 64.6%	173 63.4%	523 64.2%
>=65 years	192 35.4%	100 36.6%	292 35.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.8 (14.47)	58.6 (13.73)	58.8 (14.22)
Sex: Female, Male (Count of Participants)
Female	211 38.9%	120 44%	331 40.6%
Male	331 61.1%	153 56%	484 59.4%

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 to 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
Arm/Group Description	Participants received peginesatide by intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study. 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 or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta 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	542	273
Baseline [N=542, 273]	11.20 (0.553)	11.21 (0.546)
Evaluation Period [N=488, 237]	11.13 (1.018)	11.05 (0.958)
Change from Baseline [N=488, 237]	-0.07 (1.009)	-0.17 (1.000)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide, Epoetin
	Comments	The sample size for this study has been 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 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	0.10
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.078
	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
Arm/Group Description	Participants received peginesatide by intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study. 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 or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta 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	542	273
Number [percentage of participants]	0.077 0%	0.099 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide, Epoetin
	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	0.79
	Confidence Interval	(2-Sided) 95%; 0.50 to 1.24
	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
Arm/Group Description	Participants received peginesatide by intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study. 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 or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta 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	542	273
Number [percentage of participants]	0.635 0.1%	0.659 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide, Epoetin
	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	0.96
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Peginesatide		Epoetin
Arm/Group Description	Participants received peginesatide by intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study. 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 or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta 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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Peginesatide		Epoetin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	268/542 (49.4%)		141/273 (51.6%)
Blood and lymphatic system disorders
Anaemia	5/542 (0.9%)		5/273 (1.8%)
Coagulopathy	2/542 (0.4%)		1/273 (0.4%)
Hypoprothrombinaemia	0/542 (0%)		1/273 (0.4%)
Leukocytosis	1/542 (0.2%)		0/273 (0%)
Leukopenia	0/542 (0%)		1/273 (0.4%)
Pancytopenia	1/542 (0.2%)		0/273 (0%)
Thrombocytopenia	1/542 (0.2%)		0/273 (0%)
Cardiac disorders
Cardiac failure congestive	24/542 (4.4%)		17/273 (6.2%)
Acute myocardial infarction	11/542 (2%)		9/273 (3.3%)
Cardiac arrest	8/542 (1.5%)		9/273 (3.3%)
Atrial fibrillation	8/542 (1.5%)		8/273 (2.9%)
Coronary artery disease	8/542 (1.5%)		7/273 (2.6%)
Myocardial infarction	10/542 (1.8%)		4/273 (1.5%)
Angina pectoris	7/542 (1.3%)		2/273 (0.7%)
Cardio-respiratory arrest	4/542 (0.7%)		3/273 (1.1%)
Bradycardia	5/542 (0.9%)		1/273 (0.4%)
Cardiac failure	4/542 (0.7%)		2/273 (0.7%)
Angina unstable	3/542 (0.6%)		2/273 (0.7%)
Arrhythmia	3/542 (0.6%)		1/273 (0.4%)
Sick sinus syndrome	1/542 (0.2%)		3/273 (1.1%)
Acute coronary syndrome	2/542 (0.4%)		1/273 (0.4%)
Pericarditis	1/542 (0.2%)		2/273 (0.7%)
Supraventricular tachycardia	2/542 (0.4%)		1/273 (0.4%)
Atrial flutter	0/542 (0%)		2/273 (0.7%)
Atrial thrombosis	1/542 (0.2%)		1/273 (0.4%)
Atrioventricular block complete	2/542 (0.4%)		0/273 (0%)
Cardiac tamponade	2/542 (0.4%)		0/273 (0%)
Cardiogenic shock	1/542 (0.2%)		1/273 (0.4%)
Myocardial ischaemia	1/542 (0.2%)		1/273 (0.4%)
Nodal arrhythmia	2/542 (0.4%)		0/273 (0%)
Tachycardia	0/542 (0%)		2/273 (0.7%)
Aortic valve stenosis	0/542 (0%)		1/273 (0.4%)
Arteriosclerosis coronary artery	0/542 (0%)		1/273 (0.4%)
Atrial tachycardia	1/542 (0.2%)		0/273 (0%)
Cardiac failure acute	0/542 (0%)		1/273 (0.4%)
Cardiomyopathy	0/542 (0%)		1/273 (0.4%)
Cardiopulmonary failure	0/542 (0%)		1/273 (0.4%)
Diastolic dysfunction	1/542 (0.2%)		0/273 (0%)
Dilatation ventricular	0/542 (0%)		1/273 (0.4%)
Ischaemic cardiomyopathy	1/542 (0.2%)		0/273 (0%)
Left ventricular dysfunction	1/542 (0.2%)		0/273 (0%)
Mitral valve disease	1/542 (0.2%)		0/273 (0%)
Palpitations	1/542 (0.2%)		0/273 (0%)
Pericardial effusion	0/542 (0%)		1/273 (0.4%)
Pericarditis uraemic	0/542 (0%)		1/273 (0.4%)
Sinus tachycardia	0/542 (0%)		1/273 (0.4%)
Ventricular fibrillation	0/542 (0%)		1/273 (0.4%)
Ventricular tachycardia	1/542 (0.2%)		0/273 (0%)
Congenital, familial and genetic disorders
Congenital cystic kidney disease	1/542 (0.2%)		0/273 (0%)
Endocrine disorders
Hyperparathyroidism	2/542 (0.4%)		0/273 (0%)
Hyperparathyroidism secondary	0/542 (0%)		1/273 (0.4%)
Hyperparathyroidism tertiary	1/542 (0.2%)		0/273 (0%)
Hypothyroidism	1/542 (0.2%)		0/273 (0%)
Eye disorders
Vision blurred	0/542 (0%)		2/273 (0.7%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	9/542 (1.7%)		4/273 (1.5%)
Gastritis erosive	4/542 (0.7%)		3/273 (1.1%)
Gastrooesophageal reflux disease	2/542 (0.4%)		2/273 (0.7%)
Upper gastrointestinal haemorrhage	3/542 (0.6%)		1/273 (0.4%)
Ascites	1/542 (0.2%)		2/273 (0.7%)
Colitis	3/542 (0.6%)		0/273 (0%)
Diarrhoea	2/542 (0.4%)		1/273 (0.4%)
Duodenal ulcer	2/542 (0.4%)		1/273 (0.4%)
Gastric ulcer	2/542 (0.4%)		1/273 (0.4%)
Gastritis	2/542 (0.4%)		1/273 (0.4%)
Appendicitis perforated	1/542 (0.2%)		1/273 (0.4%)
Diabetic gastroparesis	2/542 (0.4%)		0/273 (0%)
Diverticulum	1/542 (0.2%)		1/273 (0.4%)
Impaired gastric emptying	2/542 (0.4%)		0/273 (0%)
Large intestinal ulcer	1/542 (0.2%)		1/273 (0.4%)
Lower gastrointestinal haemorrhage	2/542 (0.4%)		0/273 (0%)
Oesophagitis	2/542 (0.4%)		0/273 (0%)
Oesophagitis haemorrhagic	1/542 (0.2%)		1/273 (0.4%)
Pancreatitis	2/542 (0.4%)		0/273 (0%)
Pancreatitis acute	1/542 (0.2%)		1/273 (0.4%)
Rectal haemorrhage	2/542 (0.4%)		0/273 (0%)
Vomiting	2/542 (0.4%)		0/273 (0%)
Abdominal discomfort	0/542 (0%)		1/273 (0.4%)
Abdominal mass	1/542 (0.2%)		0/273 (0%)
Abdominal pain	0/542 (0%)		1/273 (0.4%)
Colitis ischaemic	1/542 (0.2%)		0/273 (0%)
Colonic polyp	1/542 (0.2%)		0/273 (0%)
Constipation	1/542 (0.2%)		0/273 (0%)
Crohn's disease	1/542 (0.2%)		0/273 (0%)
Diverticulum intestinal haemorrhagic	0/542 (0%)		1/273 (0.4%)
Duodenal ulcer haemorrhage	1/542 (0.2%)		0/273 (0%)
Erosive oesophagitis	1/542 (0.2%)		0/273 (0%)
Gastritis atrophic	1/542 (0.2%)		0/273 (0%)
Gastroduodenitis	1/542 (0.2%)		0/273 (0%)
Gastrointestinal necrosis	1/542 (0.2%)		0/273 (0%)
Gingivitis ulcerative	1/542 (0.2%)		0/273 (0%)
Haematemesis	1/542 (0.2%)		0/273 (0%)
Haematochezia	0/542 (0%)		1/273 (0.4%)
Haemorrhoidal haemorrhage	0/542 (0%)		1/273 (0.4%)
Hiatus hernia	0/542 (0%)		1/273 (0.4%)
Inguinal hernia	1/542 (0.2%)		0/273 (0%)
Intestinal angina	1/542 (0.2%)		0/273 (0%)
Intestinal haemorrhage	0/542 (0%)		1/273 (0.4%)
Intestinal obstruction	0/542 (0%)		1/273 (0.4%)
Mallory-Weiss syndrome	1/542 (0.2%)		0/273 (0%)
Nausea	1/542 (0.2%)		0/273 (0%)
Oesophageal achalasia	1/542 (0.2%)		0/273 (0%)
Oesophageal ulcer	1/542 (0.2%)		0/273 (0%)
Oesophagitis ulcerative	1/542 (0.2%)		0/273 (0%)
Peptic ulcer perforation	1/542 (0.2%)		0/273 (0%)
Peritonitis	1/542 (0.2%)		0/273 (0%)
Small intestinal haemorrhage	0/542 (0%)		1/273 (0.4%)
Small intestinal obstruction	1/542 (0.2%)		0/273 (0%)
Umbilical hernia, obstructive	1/542 (0.2%)		0/273 (0%)
General disorders
Non-cardiac chest pain	10/542 (1.8%)		4/273 (1.5%)
Chest pain	8/542 (1.5%)		5/273 (1.8%)
Pyrexia	2/542 (0.4%)		5/273 (1.8%)
Death	3/542 (0.6%)		2/273 (0.7%)
Asthenia	3/542 (0.6%)		1/273 (0.4%)
Catheter related complication	1/542 (0.2%)		2/273 (0.7%)
Catheter thrombosis	2/542 (0.4%)		1/273 (0.4%)
Chills	1/542 (0.2%)		0/273 (0%)
Gait disturbance	0/542 (0%)		1/273 (0.4%)
Generalised oedema	0/542 (0%)		1/273 (0.4%)
Ischaemic ulcer	1/542 (0.2%)		0/273 (0%)
Oedema	1/542 (0.2%)		0/273 (0%)
Sudden cardiac death	1/542 (0.2%)		0/273 (0%)
Systemic inflammatory response syndrome	0/542 (0%)		1/273 (0.4%)
Hepatobiliary disorders
Cholecystitis acute	3/542 (0.6%)		1/273 (0.4%)
Cholecystitis	1/542 (0.2%)		1/273 (0.4%)
Cholelithiasis	1/542 (0.2%)		1/273 (0.4%)
Bile duct stone	1/542 (0.2%)		0/273 (0%)
Cholangitis acute	1/542 (0.2%)		0/273 (0%)
Cholecystitis chronic	1/542 (0.2%)		0/273 (0%)
Hepatitis	1/542 (0.2%)		0/273 (0%)
Immune system disorders
Anaphylactic reaction	1/542 (0.2%)		0/273 (0%)
Anaphylactic shock	1/542 (0.2%)		0/273 (0%)
Contrast media allergy	1/542 (0.2%)		0/273 (0%)
Infections and infestations
Pneumonia	31/542 (5.7%)		12/273 (4.4%)
Sepsis	20/542 (3.7%)		13/273 (4.8%)
Cellulitis	19/542 (3.5%)		5/273 (1.8%)
Gastroenteritis	6/542 (1.1%)		4/273 (1.5%)
Bacteraemia	7/542 (1.3%)		2/273 (0.7%)
Urinary tract infection	7/542 (1.3%)		1/273 (0.4%)
Bronchitis	5/542 (0.9%)		2/273 (0.7%)
Osteomyelitis	4/542 (0.7%)		3/273 (1.1%)
Catheter related infection	4/542 (0.7%)		2/273 (0.7%)
Gangrene	4/542 (0.7%)		2/273 (0.7%)
Arteriovenous fistula site infection	2/542 (0.4%)		3/273 (1.1%)
Clostridium difficile colitis	5/542 (0.9%)		0/273 (0%)
Septic shock	2/542 (0.4%)		3/273 (1.1%)
Bronchopneumonia	2/542 (0.4%)		2/273 (0.7%)
Localised infection	2/542 (0.4%)		2/273 (0.7%)
Arteriovenous graft site infection	2/542 (0.4%)		1/273 (0.4%)
Pneumonia staphylococcal	1/542 (0.2%)		2/273 (0.7%)
Staphylococcal bacteraemia	2/542 (0.4%)		1/273 (0.4%)
Staphylococcal sepsis	1/542 (0.2%)		2/273 (0.7%)
Wound infection staphylococcal	1/542 (0.2%)		2/273 (0.7%)
Abdominal abscess	1/542 (0.2%)		1/273 (0.4%)
Abscess	2/542 (0.4%)		0/273 (0%)
Appendicitis	0/542 (0%)		2/273 (0.7%)
Arthritis infective	2/542 (0.4%)		0/273 (0%)
Clostridium difficile sepsis	2/542 (0.4%)		0/273 (0%)
Diabetic foot infection	2/542 (0.4%)		0/273 (0%)
Diverticulitis	1/542 (0.2%)		1/273 (0.4%)
Empyema	2/542 (0.4%)		0/273 (0%)
Endocarditis	1/542 (0.2%)		1/273 (0.4%)
Enterococcal sepsis	2/542 (0.4%)		0/273 (0%)
Hepatitis B	2/542 (0.4%)		0/273 (0%)
Influenza	2/542 (0.4%)		0/273 (0%)
Lobar pneumonia	1/542 (0.2%)		1/273 (0.4%)
Lower respiratory tract infection	2/542 (0.4%)		0/273 (0%)
Necrotising fasciitis	1/542 (0.2%)		1/273 (0.4%)
Osteomyelitis chronic	1/542 (0.2%)		1/273 (0.4%)
Pyelonephritis chronic	0/542 (0%)		2/273 (0.7%)
Sepsis syndrome	1/542 (0.2%)		1/273 (0.4%)
Staphylococcal infection	1/542 (0.2%)		1/273 (0.4%)
Upper respiratory tract infection	1/542 (0.2%)		1/273 (0.4%)
Viral upper respiratory tract infection	1/542 (0.2%)		1/273 (0.4%)
Abscess limb	0/542 (0%)		1/273 (0.4%)
Bacterial sepsis	0/542 (0%)		1/273 (0.4%)
Bronchitis bacterial	1/542 (0.2%)		0/273 (0%)
Cystitis	1/542 (0.2%)		0/273 (0%)
Diabetic gangrene	0/542 (0%)		1/273 (0.4%)
Groin abscess	1/542 (0.2%)		0/273 (0%)
Hepatitis C	1/542 (0.2%)		0/273 (0%)
Herpes zoster	0/542 (0%)		1/273 (0.4%)
Incision site infection	1/542 (0.2%)		0/273 (0%)
Infected skin ulcer	0/542 (0%)		1/273 (0.4%)
Klebsiella bacteraemia	1/542 (0.2%)		0/273 (0%)
Liver abscess	1/542 (0.2%)		0/273 (0%)
Mastoiditis	1/542 (0.2%)		0/273 (0%)
Nasopharyngitis	0/542 (0%)		1/273 (0.4%)
Otitis externa	0/542 (0%)		1/273 (0.4%)
Perinephric abscess	1/542 (0.2%)		0/273 (0%)
Perirectal abscess	1/542 (0.2%)		0/273 (0%)
Pneumonia fungal	1/542 (0.2%)		0/273 (0%)
Post procedural sepsis	1/542 (0.2%)		0/273 (0%)
Postoperative abscess	1/542 (0.2%)		0/273 (0%)
Postoperative wound infection	1/542 (0.2%)		0/273 (0%)
Respiratory tract infection	1/542 (0.2%)		0/273 (0%)
Skin infection	0/542 (0%)		1/273 (0.4%)
Streptococcal bacteraemia	1/542 (0.2%)		0/273 (0%)
Streptococcal sepsis	0/542 (0%)		1/273 (0.4%)
Subcutaneous abscess	0/542 (0%)		1/273 (0.4%)
Tooth abscess	0/542 (0%)		1/273 (0.4%)
Tuberculous pleurisy	0/542 (0%)		1/273 (0.4%)
Viraemia	0/542 (0%)		1/273 (0.4%)
Viral infection	1/542 (0.2%)		0/273 (0%)
Wound sepsis	1/542 (0.2%)		0/273 (0%)
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis	10/542 (1.8%)		6/273 (2.2%)
Arteriovenous fistula site haemorrhage	5/542 (0.9%)		2/273 (0.7%)
Arteriovenous fistula site complication	1/542 (0.2%)		5/273 (1.8%)
Arteriovenous graft thrombosis	3/542 (0.6%)		3/273 (1.1%)
Arteriovenous graft site haemorrhage	4/542 (0.7%)		1/273 (0.4%)
Hip fracture	3/542 (0.6%)		2/273 (0.7%)
Vascular graft complication	4/542 (0.7%)		1/273 (0.4%)
Femur fracture	1/542 (0.2%)		3/273 (1.1%)
Arteriovenous fistula aneurysm	3/542 (0.6%)		0/273 (0%)
Complications of transplanted kidney	3/542 (0.6%)		0/273 (0%)
Fall	2/542 (0.4%)		1/273 (0.4%)
Pelvic fracture	1/542 (0.2%)		1/273 (0.4%)
Post procedural haemorrhage	2/542 (0.4%)		0/273 (0%)
Procedural hypotension	1/542 (0.2%)		1/273 (0.4%)
Subdural haematoma	0/542 (0%)		2/273 (0.7%)
Therapeutic product contamination	2/542 (0.4%)		0/273 (0%)
Ankle fracture	1/542 (0.2%)		0/273 (0%)
Arteriovenous fistula occlusion	1/542 (0.2%)		0/273 (0%)
Cervical vertebral fracture	1/542 (0.2%)		0/273 (0%)
Concussion	1/542 (0.2%)		0/273 (0%)
Delayed recovery from anaesthesia	1/542 (0.2%)		0/273 (0%)
Drug toxicity	1/542 (0.2%)		0/273 (0%)
Excoriation	0/542 (0%)		1/273 (0.4%)
Femoral neck fracture	1/542 (0.2%)		0/273 (0%)
Fibula fracture	1/542 (0.2%)		0/273 (0%)
Foot fracture	1/542 (0.2%)		0/273 (0%)
Graft thrombosis	1/542 (0.2%)		0/273 (0%)
Humerus fracture	0/542 (0%)		1/273 (0.4%)
Implantable defibrillator malfunction	1/542 (0.2%)		0/273 (0%)
Joint injury	0/542 (0%)		1/273 (0.4%)
Lower limb fracture	1/542 (0.2%)		0/273 (0%)
Muscle strain	1/542 (0.2%)		0/273 (0%)
Operative haemorrhage	1/542 (0.2%)		0/273 (0%)
Patella fracture	1/542 (0.2%)		0/273 (0%)
Post procedural complication	1/542 (0.2%)		0/273 (0%)
Postoperative wound complication	1/542 (0.2%)		0/273 (0%)
Procedural nausea	1/542 (0.2%)		0/273 (0%)
Procedural vomiting	1/542 (0.2%)		0/273 (0%)
Renal haematoma	0/542 (0%)		1/273 (0.4%)
Road traffic accident	1/542 (0.2%)		0/273 (0%)
Shunt thrombosis	1/542 (0.2%)		0/273 (0%)
Skin laceration	0/542 (0%)		1/273 (0.4%)
Stent occlusion	1/542 (0.2%)		0/273 (0%)
Subcutaneous haematoma	1/542 (0.2%)		0/273 (0%)
Therapeutic agent toxicity	1/542 (0.2%)		0/273 (0%)
Thermal burn	1/542 (0.2%)		0/273 (0%)
Tibia fracture	1/542 (0.2%)		0/273 (0%)
Transplant failure	1/542 (0.2%)		0/273 (0%)
Traumatic haematoma	1/542 (0.2%)		0/273 (0%)
Upper limb fracture	0/542 (0%)		1/273 (0.4%)
Urinary anastomotic leak	1/542 (0.2%)		0/273 (0%)
Wrist fracture	0/542 (0%)		1/273 (0.4%)
Investigations
Blood pressure increased	1/542 (0.2%)		0/273 (0%)
Cardiac enzymes increased	1/542 (0.2%)		0/273 (0%)
Electrocardiogram QT prolonged	1/542 (0.2%)		0/273 (0%)
Weight decreased	1/542 (0.2%)		0/273 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	25/542 (4.6%)		8/273 (2.9%)
Fluid overload	20/542 (3.7%)		9/273 (3.3%)
Hypoglycaemia	8/542 (1.5%)		6/273 (2.2%)
Diabetic foot	4/542 (0.7%)		1/273 (0.4%)
Calciphylaxis	3/542 (0.6%)		0/273 (0%)
Diabetes mellitus inadequate control	1/542 (0.2%)		1/273 (0.4%)
Diabetic ketoacidosis	1/542 (0.2%)		1/273 (0.4%)
Hypocalcaemia	0/542 (0%)		2/273 (0.7%)
Hypomagnesaemia	2/542 (0.4%)		0/273 (0%)
Malnutrition	2/542 (0.4%)		0/273 (0%)
Acidosis	0/542 (0%)		1/273 (0.4%)
Cachexia	0/542 (0%)		1/273 (0.4%)
Dehydration	0/542 (0%)		1/273 (0.4%)
Diabetes mellitus	1/542 (0.2%)		0/273 (0%)
Fluid retention	0/542 (0%)		1/273 (0.4%)
Hypercalcaemia	1/542 (0.2%)		0/273 (0%)
Hyperglycaemia	0/542 (0%)		1/273 (0.4%)
Hypovolaemia	1/542 (0.2%)		0/273 (0%)
Metabolic acidosis	1/542 (0.2%)		0/273 (0%)
Vitamin B12 deficiency	1/542 (0.2%)		0/273 (0%)
Musculoskeletal and connective tissue disorders
Back pain	2/542 (0.4%)		1/273 (0.4%)
Muscular weakness	1/542 (0.2%)		2/273 (0.7%)
Osteoarthritis	3/542 (0.6%)		0/273 (0%)
Arthralgia	0/542 (0%)		1/273 (0.4%)
Diabetic amyotrophy	0/542 (0%)		1/273 (0.4%)
Intervertebral disc degeneration	0/542 (0%)		1/273 (0.4%)
Rhabdomyolysis	1/542 (0.2%)		0/273 (0%)
Scleroderma	1/542 (0.2%)		0/273 (0%)
Spinal column stenosis	1/542 (0.2%)		0/273 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma	1/542 (0.2%)		1/273 (0.4%)
Anal neoplasm	1/542 (0.2%)		0/273 (0%)
Colon neoplasm	1/542 (0.2%)		0/273 (0%)
Diffuse large B-cell lymphoma	0/542 (0%)		1/273 (0.4%)
Hepatic neoplasm malignant	0/542 (0%)		1/273 (0.4%)
Lung neoplasm	1/542 (0.2%)		0/273 (0%)
Neuroendocrine tumour	1/542 (0.2%)		0/273 (0%)
Non-small cell lung cancer	0/542 (0%)		1/273 (0.4%)
Non-small cell lung cancer metastatic	1/542 (0.2%)		0/273 (0%)
Oesophageal carcinoma	1/542 (0.2%)		0/273 (0%)
Pancreatic carcinoma	1/542 (0.2%)		0/273 (0%)
Pancreatic neoplasm	1/542 (0.2%)		0/273 (0%)
Tongue neoplasm malignant stage unspecified	1/542 (0.2%)		0/273 (0%)
Transitional cell carcinoma	1/542 (0.2%)		0/273 (0%)
Nervous system disorders
Cerebrovascular accident	11/542 (2%)		4/273 (1.5%)
Syncope	5/542 (0.9%)		2/273 (0.7%)
Convulsion	3/542 (0.6%)		3/273 (1.1%)
Transient ischaemic attack	1/542 (0.2%)		3/273 (1.1%)
Anoxic encephalopathy	2/542 (0.4%)		1/273 (0.4%)
Cerebral haemorrhage	0/542 (0%)		2/273 (0.7%)
Cerebral infarction	2/542 (0.4%)		0/273 (0%)
Encephalopathy	2/542 (0.4%)		0/273 (0%)
Ischaemic stroke	1/542 (0.2%)		1/273 (0.4%)
Presyncope	2/542 (0.4%)		0/273 (0%)
Subarachnoid haemorrhage	0/542 (0%)		2/273 (0.7%)
Brain oedema	0/542 (0%)		1/273 (0.4%)
Brain stem infarction	0/542 (0%)		1/273 (0.4%)
Carotid artery stenosis	0/542 (0%)		1/273 (0.4%)
Cerebral haematoma	1/542 (0.2%)		0/273 (0%)
Cerebral ischaemia	1/542 (0.2%)		0/273 (0%)
Coma	1/542 (0.2%)		0/273 (0%)
Diabetic autonomic neuropathy	1/542 (0.2%)		0/273 (0%)
Dizziness	1/542 (0.2%)		0/273 (0%)
Embolic stroke	0/542 (0%)		1/273 (0.4%)
Facial palsy	1/542 (0.2%)		0/273 (0%)
Grand mal convulsion	1/542 (0.2%)		0/273 (0%)
Haemorrhage intracranial	0/542 (0%)		1/273 (0.4%)
Headache	1/542 (0.2%)		0/273 (0%)
Hypertensive encephalopathy	1/542 (0.2%)		0/273 (0%)
Hypoglycaemic encephalopathy	0/542 (0%)		1/273 (0.4%)
Hypoxic encephalopathy	1/542 (0.2%)		0/273 (0%)
IIIrd nerve paralysis	1/542 (0.2%)		0/273 (0%)
Intracranial aneurysm	1/542 (0.2%)		0/273 (0%)
Myelopathy	1/542 (0.2%)		0/273 (0%)
Neuropathy peripheral	1/542 (0.2%)		0/273 (0%)
Neurotoxicity	1/542 (0.2%)		0/273 (0%)
Parkinson's disease	0/542 (0%)		1/273 (0.4%)
Radiculopathy	0/542 (0%)		1/273 (0.4%)
Sensory disturbance	0/542 (0%)		1/273 (0.4%)
Syncope vasovagal	0/542 (0%)		1/273 (0.4%)
Tardive dyskinesia	1/542 (0.2%)		0/273 (0%)
Thrombotic stroke	1/542 (0.2%)		0/273 (0%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/542 (0.2%)		0/273 (0%)
Psychiatric disorders
Mental status changes	5/542 (0.9%)		3/273 (1.1%)
Acute psychosis	1/542 (0.2%)		0/273 (0%)
Depression	1/542 (0.2%)		0/273 (0%)
Hallucination	1/542 (0.2%)		0/273 (0%)
Renal and urinary disorders
Azotaemia	2/542 (0.4%)		1/273 (0.4%)
Renal failure chronic	3/542 (0.6%)		0/273 (0%)
Haematuria	1/542 (0.2%)		0/273 (0%)
Hydronephrosis	1/542 (0.2%)		0/273 (0%)
Pyuria	1/542 (0.2%)		0/273 (0%)
Renal failure acute	1/542 (0.2%)		0/273 (0%)
Renal haemorrhage	1/542 (0.2%)		0/273 (0%)
Ureteric dilatation	1/542 (0.2%)		0/273 (0%)
Urethral stenosis	1/542 (0.2%)		0/273 (0%)
Urinary retention	1/542 (0.2%)		0/273 (0%)
Urinary tract inflammation	1/542 (0.2%)		0/273 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/542 (0.2%)		0/273 (0%)
Penile necrosis	0/542 (0%)		1/273 (0.4%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	16/542 (3%)		7/273 (2.6%)
Pulmonary oedema	8/542 (1.5%)		9/273 (3.3%)
Pleural effusion	7/542 (1.3%)		2/273 (0.7%)
Acute respiratory failure	6/542 (1.1%)		0/273 (0%)
Chronic obstructive pulmonary disease	3/542 (0.6%)		3/273 (1.1%)
Pulmonary embolism	3/542 (0.6%)		2/273 (0.7%)
Pneumonia aspiration	3/542 (0.6%)		1/273 (0.4%)
Asthma	2/542 (0.4%)		0/273 (0%)
Haemothorax	1/542 (0.2%)		1/273 (0.4%)
Pneumonitis	2/542 (0.4%)		0/273 (0%)
Respiratory arrest	1/542 (0.2%)		1/273 (0.4%)
Acute pulmonary oedema	0/542 (0%)		1/273 (0.4%)
Asphyxia	1/542 (0.2%)		0/273 (0%)
Aspiration	0/542 (0%)		1/273 (0.4%)
Choking	1/542 (0.2%)		0/273 (0%)
Cough	0/542 (0%)		1/273 (0.4%)
Dyspnoea	1/542 (0.2%)		0/273 (0%)
Haemoptysis	1/542 (0.2%)		0/273 (0%)
Hypoxia	0/542 (0%)		1/273 (0.4%)
Pleurisy	1/542 (0.2%)		0/273 (0%)
Pneumothorax	0/542 (0%)		1/273 (0.4%)
Pulmonary cavitation	1/542 (0.2%)		0/273 (0%)
Pulmonary hypertension	1/542 (0.2%)		0/273 (0%)
Pulmonary mass	1/542 (0.2%)		0/273 (0%)
Respiratory distress	0/542 (0%)		1/273 (0.4%)
Skin and subcutaneous tissue disorders
Skin ulcer	2/542 (0.4%)		0/273 (0%)
Angioedema	1/542 (0.2%)		0/273 (0%)
Decubitus ulcer	0/542 (0%)		1/273 (0.4%)
Dry gangrene	0/542 (0%)		1/273 (0.4%)
Pruritus	1/542 (0.2%)		0/273 (0%)
Skin haemorrhage	1/542 (0.2%)		0/273 (0%)
Skin necrosis	0/542 (0%)		1/273 (0.4%)
Vascular disorders
Hypotension	11/542 (2%)		3/273 (1.1%)
Hypertensive crisis	8/542 (1.5%)		4/273 (1.5%)
Hypertension	3/542 (0.6%)		3/273 (1.1%)
Deep vein thrombosis	4/542 (0.7%)		1/273 (0.4%)
Malignant hypertension	2/542 (0.4%)		3/273 (1.1%)
Arteriosclerosis	2/542 (0.4%)		1/273 (0.4%)
Peripheral arterial occlusive disease	2/542 (0.4%)		1/273 (0.4%)
Peripheral ischaemia	2/542 (0.4%)		1/273 (0.4%)
Peripheral vascular disorder	3/542 (0.6%)		0/273 (0%)
Hypertensive emergency	2/542 (0.4%)		0/273 (0%)
Orthostatic hypotension	1/542 (0.2%)		1/273 (0.4%)
Shock haemorrhagic	1/542 (0.2%)		1/273 (0.4%)
Aortic aneurysm	1/542 (0.2%)		0/273 (0%)
Arterial thrombosis	1/542 (0.2%)		0/273 (0%)
Arterial thrombosis limb	1/542 (0.2%)		0/273 (0%)
Circulatory collapse	1/542 (0.2%)		0/273 (0%)
Embolism	1/542 (0.2%)		0/273 (0%)
Extremity necrosis	1/542 (0.2%)		0/273 (0%)
Femoral artery occlusion	1/542 (0.2%)		0/273 (0%)
Haematoma	1/542 (0.2%)		0/273 (0%)
Lymphocele	1/542 (0.2%)		0/273 (0%)
Lymphoedema	1/542 (0.2%)		0/273 (0%)
Shock	1/542 (0.2%)		0/273 (0%)
Steal syndrome	0/542 (0%)		1/273 (0.4%)
Superior vena caval occlusion	0/542 (0%)		1/273 (0.4%)
Vascular pseudoaneurysm	1/542 (0.2%)		0/273 (0%)
Other (Not Including Serious) Adverse Events
	Peginesatide		Epoetin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	445/542 (82.1%)		222/273 (81.3%)
Gastrointestinal disorders
Nausea	96/542 (17.7%)		54/273 (19.8%)
Diarrhoea	91/542 (16.8%)		47/273 (17.2%)
Vomiting	74/542 (13.7%)		38/273 (13.9%)
Constipation	56/542 (10.3%)		27/273 (9.9%)
Abdominal pain	51/542 (9.4%)		21/273 (7.7%)
Abdominal pain upper	29/542 (5.4%)		11/273 (4%)
General disorders
Pyrexia	61/542 (11.3%)		29/273 (10.6%)
Oedema peripheral	53/542 (9.8%)		18/273 (6.6%)
Chest pain	43/542 (7.9%)		16/273 (5.9%)
Asthenia	41/542 (7.6%)		12/273 (4.4%)
Fatigue	39/542 (7.2%)		21/273 (7.7%)
Pain	30/542 (5.5%)		10/273 (3.7%)
Infections and infestations
Upper respiratory tract infection	53/542 (9.8%)		24/273 (8.8%)
Nasopharyngitis	46/542 (8.5%)		24/273 (8.8%)
Urinary tract infection	21/542 (3.9%)		15/273 (5.5%)
Injury, poisoning and procedural complications
Arteriovenous fistula site complication	90/542 (16.6%)		40/273 (14.7%)
Procedural hypotension	82/542 (15.1%)		43/273 (15.8%)
Vascular graft complication	46/542 (8.5%)		19/273 (7%)
Arteriovenous fistula thrombosis	42/542 (7.7%)		21/273 (7.7%)
Procedural hypertension	36/542 (6.6%)		17/273 (6.2%)
Arteriovenous graft thrombosis	33/542 (6.1%)		16/273 (5.9%)
Arteriovenous fistula site haemorrhage	30/542 (5.5%)		19/273 (7%)
Fall	30/542 (5.5%)		11/273 (4%)
Metabolism and nutrition disorders
Hyperkalaemia	41/542 (7.6%)		16/273 (5.9%)
Musculoskeletal and connective tissue disorders
Muscle spasms	106/542 (19.6%)		52/273 (19%)
Arthralgia	63/542 (11.6%)		27/273 (9.9%)
Back pain	61/542 (11.3%)		23/273 (8.4%)
Pain in extremity	61/542 (11.3%)		36/273 (13.2%)
Musculoskeletal pain	34/542 (6.3%)		15/273 (5.5%)
Nervous system disorders
Headache	86/542 (15.9%)		46/273 (16.8%)
Dizziness	43/542 (7.9%)		25/273 (9.2%)
Psychiatric disorders
Insomnia	38/542 (7%)		23/273 (8.4%)
Anxiety	28/542 (5.2%)		23/273 (8.4%)
Depression	23/542 (4.2%)		14/273 (5.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	96/542 (17.7%)		50/273 (18.3%)
Cough	69/542 (12.7%)		35/273 (12.8%)
Skin and subcutaneous tissue disorders
Pruritus	36/542 (6.6%)		16/273 (5.9%)
Vascular disorders
Hypertension	84/542 (15.5%)		31/273 (11.4%)
Hypotension	72/542 (13.3%)		42/273 (15.4%)

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.