A Study of Methoxy Polyethylene Glycol-epoetin Beta (Mircera) in Participants With Chronic Kidney Disease (PRIMAVERA)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01194154
• Collaborator: (none)
• Enrollment: 241
• Locations: 33
• Arms: 2
• Actual Duration (Months): 54
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This randomized, single-blind, proof-of-concept study will investigate the protective effects of early treatment with Mircera in participants with chronic kidney disease on renal disease progression. Participants will be randomly assigned to receive 30 microgram (mcg) Mircera as subcutaneous injection once monthly or matching placebo. Depending on change of hemoglobin values, the dose of Mircera can be adjusted to 50 mcg or 75 mcg once monthly. The anticipated time on study treatment is 24 months.

Condition or Disease	Intervention/Treatment	Phase
Kidney Disease, Chronic	Drug: Methoxy polyethylene glycol-epoetin beta; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 241 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled, Single-blind, Proof-of-concept-study to Investigate the Protective Effects of Early Treatment With C.E.R.A. in Patients With Chronic Kidney Disease on Renal Disease Progression (PRIMAVERA-Study)
• Actual Study Start Date: Sep 30, 2010
• Actual Primary Completion Date: Mar 31, 2015
• Actual Study Completion Date: Mar 31, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mircera	Drug: Methoxy polyethylene glycol-epoetin beta; Methoxy polyethylene glycol-epoetin beta 30 microgram (mcg) subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 gram (g)/ deciliter (dL).; Other Names: Mircera, C.E.R.A.
Placebo Comparator: Placebo	Drug: Placebo; Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.

Outcome Measures

Primary Outcome Measures

1. Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Modification of Diet in Renal Disease With 4 Variables (MDRD-4) [24 months]

   The yearly reduction in eGFR was calculated using the MDRD-4 formula. This formula is based on age, sex, and serum creatinine and eGFR values are calculated as follows: GFR in milliliter per minute (mL/min) per 1.73 meter square (m^2) = 175 x Serum Cr^-1.154 x age^-0.203 x 0.742 (if female). The yearly reduction rate (mL/min/1.73m^2 / Year) is defined as -365.25 multiplied by Beta, where Beta is the slope parameter derived for each participants separately by simple linear regression of the change from baseline in participant's eGFR measurements (from Baseline to Visit 24) on the actual day of measurement.

Secondary Outcome Measures

1. Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) [24 months]

   The eGFR value calculated using the CKD-EPI equation. The formula used is based on age, sex, ethnicity, and serum creatinine and eGFR values are calculated as follows: GFR in mL/min per 1.73 m^2 = 141 x min (SerumCr/k; 1)^a x max(SerumCr/k; 1)^(-1.209) x 0.993^age x F x B, where k=0.7 for female (else=0.9); a=-0.329 for female (else=-0.411), F=1.018 for female (else=1), B=1.159 for black (else=1), min/max=minimum/maximum of listed values. The Yearly Reduction Rate (mL/min/1.73m^2 / Year) is defined as -365.25 x Beta, where Beta is the slope parameter derived for each participant separately by simple linear regression of the change from baseline in participant's eGFR measurements (from Baseline to Visit 24) on the actual day of measurement.

2. Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Month 24 [Baseline, Month 24]

   Creatinine clearance was calculated according to the Cockcroft and Gault Formula. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is greater than or equal to (>=) 90 mL/min. Change from baseline=CC at Week X minus CC at baseline where higher scores represented improved renal function.

3. Change From Baseline in Serum Creatinine Concentration at Month 24 [Baseline, Month 24]

   Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent.

4. Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Month 24 [Baseline, Month 24]

   UACR is defined as the ratio: milligram of albumin per gram of creatinine. The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.

5. Change From Baseline in Serum Cystatin C Concentration at Month 24 [Baseline, Month 24]

   Cystatin C is a protein which is mainly used as a biomarker of kidney function. If kidney function and GFR decline, the blood levels of cystatin C rise.

6. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [24 months]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability or incapacity; and congenital anomaly. Percentage of participants with AEs included participants affected with both SAEs and non-SAEs.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• For diabetic participants: Type 2 diabetes mellitus with glycated hemoglobin (HbA1c) greater than (>) 7% or anti-diabetic treatment

• For renal allograft recipients: Status at least 6 months post transplantation

• Chronic kidney disease stage III

• Urinary albumin-to-creatinine ratio less than (<) 3000 milligram (mg)/gram (g) or total protein <3000 mg/ 24 hour urine sample where applicable

Exclusion Criteria:

• Hemoglobin-level < 11 or > 14 g/deciliter (dL)

• Average systolic blood pressure (SBP) > 140 millimeter of mercury (mm Hg) or average diastolic blood pressure (DBP) > 90 mm Hg

• Initiation of angiotensin converting enzyme inhibitor, angiotensin 2 receptor blocker or aliskiren treatment less than 3 months before enrolment

• Present and known iron deficiency

• HbA1c >9%

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Uniklinik RWTH Aachen; Med. Klinik II; Klinik für Nephrologie und klinische Immunologie	Aachen		Germany	52057
2	Dialysepraxis Dr. Stallforth, Dr. Kirschner, Dr. Al-Sarraf und Dr. Pawlik	Augsburg		Germany	86157
3	KfH Kuratorium für Dialyse und Nierentransplantation e.V. im Kurhaus	Bad König		Germany	64732
4	Charité - Klinikum Mitte; Medizinische Klinik Für Nephrologie	Berlin		Germany	10117
5	Charité - Campus Benjamin Franklin; Zentrum fuer Innere Medizin, Med. Klinik I	Berlin		Germany	12203
6	Gemeinschaftspraxis Dres. Erika Eger, Frank Seibt, Oliver Eike u.w. - Dialysezentrum Treptower Park	Berlin		Germany	12435
7	Dialyse-Institut Bovenden	Bovenden		Germany	37120
8	Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III	Dresden		Germany	01307
9	DaVita Clinical Research Deutschland GmbH	Düsseldorf		Germany	40210
10	Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie	Essen		Germany	45122
11	Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III	Frankfurt		Germany	60596
12	Uniklinikum Heidelberg	Heidelberg		Germany	69120
13	Dialysepraxis Prof.Dr.med. Michael Rambausek Dres. Stephan Matthias und Gabriele Kunowski - Dialysz.	Heilbronn		Germany	74076
14	Nephrologisches Zentrum Hilden am St. Josefs-Krankenhaus	Hilden		Germany	40724
15	Universitaetsklinikum des Saarlandes; Klinik f. Innere Medizin IV	Homburg/Saar		Germany	66424
16	Dres. Jan Nawka und Frank Pistrosch	Hoyerswerda		Germany	02977
17	Westpfalz-Klinikum Gmbh; Nephrologie/Transplantationsmedizin	Kaiserslautern		Germany	67655
18	PHV Patienten-Heimversorgung Dialyse-Station	Kiel		Germany	24106
19	Kliniken der Stadt Köln gGmbH Krankenhaus Merheim	Köln		Germany	51109
20	Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Transplantationszentrum	Lübeck		Germany	23562
21	Gemienschaftspraxis Dres. Leistikow, Rachti & Sandner	Mannheim		Germany	68309
22	Dres. Michael Koch Hannelore Klimke Wolfgang Kulas u.w.	Mettmann		Germany	40822
23	Klinikum Innenstadt Medizinische Klinik; Abt.Endokrinologie und Diabetologie	Muenchen		Germany	80336
24	Nierenzentrum Bogenhausen/Perlach; Praxis für Nierenheilkunde	München-Bogenhausen		Germany	81925
25	Klinikum d.Universität München Campus Großhadern	München		Germany	81377
26	Universitätsklinikum Münster Innere Medizin D	Münster		Germany	48149
27	Dres. Georg Fuchs und Nexhat Miftari	Neckarsulm		Germany	74172
28	Nephrologische Praxis Neunkirchen - Dr.med. Klemens Dorr und Artem Goldmann	Neunkirchen/Saar		Germany	66538
29	Dialysezentrum Saarlouis	Saarlouis		Germany	66740
30	Gemeinschaftspraxis Rosemarie Krämer und Lars Rothermund	Ulm		Germany	89077
31	Nephrologisches Zentrum	Velbert		Germany	42549
32	Nephrologisches Zentrum Dialyse-Institut	Villingen-Schwenningen		Germany	78052
33	KfH Kuratiorium für Dialyse und Nierentransplantation e.V.	Wiesbaden		Germany	65191

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01194154
• Other Study ID Numbers: ML22916; 2009-015114-22
• First Posted: Sep 2, 2010
• Last Update Posted: May 10, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Epoetin Alfa

Study Results

Participant Flow

Pre-assignment Detail	Total 241 participants were enrolled, 2 participants in the Mircera group and 4 participants in the placebo group did not receive medication.

Arm/Group Title	Mircera	Placebo
Arm/Group Description	Methoxy polyethylene glycol-epoetin beta 30 microgram (mcg) subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 gram (g)/ deciliter (dL).	Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Period Title: Overall Study
STARTED	117	124
Full Analysis Set	115	120
Safety Analysis Set	118	117
COMPLETED	68	91
NOT COMPLETED	49	33

Baseline Characteristics

Arm/Group Title	Mircera	Placebo	Total
Arm/Group Description	Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.	Total of all reporting groups
Overall Participants	115	120	235
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.37 (12.26)	62.97 (14.30)	63.17 (13.31)
Sex: Female, Male (Count of Participants)
Female	44 38.3%	44 36.7%	88 37.4%
Male	71 61.7%	76 63.3%	147 62.6%

Outcome Measures

1. Primary Outcome

Title	Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Modification of Diet in Renal Disease With 4 Variables (MDRD-4)
Description	The yearly reduction in eGFR was calculated using the MDRD-4 formula. This formula is based on age, sex, and serum creatinine and eGFR values are calculated as follows: GFR in milliliter per minute (mL/min) per 1.73 meter square (m^2) = 175 x Serum Cr^-1.154 x age^-0.203 x 0.742 (if female). The yearly reduction rate (mL/min/1.73m^2 / Year) is defined as -365.25 multiplied by Beta, where Beta is the slope parameter derived for each participants separately by simple linear regression of the change from baseline in participant's eGFR measurements (from Baseline to Visit 24) on the actual day of measurement.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least one dose of the study medication and provided any successive eGFR measurement.

Arm/Group Title	Mircera	Placebo
Arm/Group Description	Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Measure Participants	115	120
Least Squares Mean (95% Confidence Interval) [mL/min/1.73m^2/year]	3.04	0.82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mircera, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.657
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	treatment effect
	Estimated Value	2.21
	Confidence Interval	(2-Sided) 95%; -0.35 to 4.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	An analysis of covariance (ANCOVA) model with adjustment for baseline eGFR was used to obtain an estimate of the treatment difference.

2. Secondary Outcome

Title	Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Description	The eGFR value calculated using the CKD-EPI equation. The formula used is based on age, sex, ethnicity, and serum creatinine and eGFR values are calculated as follows: GFR in mL/min per 1.73 m^2 = 141 x min (SerumCr/k; 1)^a x max(SerumCr/k; 1)^(-1.209) x 0.993^age x F x B, where k=0.7 for female (else=0.9); a=-0.329 for female (else=-0.411), F=1.018 for female (else=1), B=1.159 for black (else=1), min/max=minimum/maximum of listed values. The Yearly Reduction Rate (mL/min/1.73m^2 / Year) is defined as -365.25 x Beta, where Beta is the slope parameter derived for each participant separately by simple linear regression of the change from baseline in participant's eGFR measurements (from Baseline to Visit 24) on the actual day of measurement.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least one dose of the study medication and provided any successive eGFR measurement.

Arm/Group Title	Mircera	Placebo
Arm/Group Description	Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Measure Participants	115	120
Least Squares Mean (95% Confidence Interval) [mL/min/1.73m^2/year]	3.02	0.78

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mircera, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.709
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	treatment effect
	Estimated Value	2.24
	Confidence Interval	(2-Sided) 95%; -0.54 to 5.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANCOVA model with adjustment for baseline eGFR was used to obtain an estimate of the treatment difference.

3. Secondary Outcome

Title	Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Month 24
Description	Creatinine clearance was calculated according to the Cockcroft and Gault Formula. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is greater than or equal to (>=) 90 mL/min. Change from baseline=CC at Week X minus CC at baseline where higher scores represented improved renal function.
Time Frame	Baseline, Month 24

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least one dose of the study medication and provided any successive eGFR measurement. Here, n=number of participants evaluable for each category.

Arm/Group Title	Mircera	Placebo
Arm/Group Description	Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Measure Participants	115	120
Baseline (n=115, 120)	53.18 (15.95)	52.48 (16.04)
Change at Month 24 (n=67, 91)	-2.97 (10.52)	-2.08 (9.72)

4. Secondary Outcome

Title	Change From Baseline in Serum Creatinine Concentration at Month 24
Description	Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent.
Time Frame	Baseline, Month 24

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least one dose of the study medication and provided any successive eGFR measurement. Here, n=number of participants evaluable for each category.

Arm/Group Title	Mircera	Placebo
Arm/Group Description	Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.	Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Measure Participants	115	120
Baseline (n=115, 120)	147.8 (31.71)	149.3 (35.67)
Change at Month 24 (n=68, 91)	7.04 (27.23)	4.04 (30.99)

5. Secondary Outcome

Title	Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Month 24
Description	UACR is defined as the ratio: milligram of albumin per gram of creatinine. The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples.
Time Frame	Baseline, Month 24

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least one dose of the study medication and provided any successive eGFR measurement. Number of Participants Analyzed (N) = number of participants evaluable and available with valid data for this outcome measure. Here, n=number of participants evaluable for each category.

Arm/Group Title	Mircera	Placebo
Arm/Group Description	Methoxy polyethylene glycol-epoetin beta 30 microgram (mcg) subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 gram (g)/ deciliter (dL).	Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Measure Participants	110	107
Baseline (n=110, 107)	261.1 (564.0)	237.3 (699.6)
Change at Month 24 (n=43, 53)	173.8 (573.3)	70.59 (546.8)

6. Secondary Outcome

Title	Change From Baseline in Serum Cystatin C Concentration at Month 24
Description	Cystatin C is a protein which is mainly used as a biomarker of kidney function. If kidney function and GFR decline, the blood levels of cystatin C rise.
Time Frame	Baseline, Month 24

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who received at least one dose of the study medication and provided any successive eGFR measurement. Here, n=number of participants evaluable for each category.

Arm/Group Title	Mircera	Placebo
Arm/Group Description	Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/ dL.	Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Measure Participants	115	120
Baseline (n=115, 120)	1.79 (0.39)	1.76 (0.46)
Change at Month 24 (n=67, 91)	0.10 (0.29)	0.02 (0.33)

7. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability or incapacity; and congenital anomaly. Percentage of participants with AEs included participants affected with both SAEs and non-SAEs.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set (SAF) included all participants who received at least one dose of study medication. Analysis for SAF was performed according to the study medication actually received (as treated population). Number of participants analyzed=participants evaluable for this measure.

Arm/Group Title	Mircera	Placebo
Arm/Group Description	Methoxy polyethylene glycol-epoetin beta 30 microgram (mcg) subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 gram (g)/ deciliter (dL).	Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Measure Participants	118	117
SAEs	35.6 31%	41.0 34.2%
AEs	84.7 73.7%	86.3 71.9%

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	The Safety Analysis Set (SAF) included all participants who received at least one dose of the study medication. Analysis for SAF was performed according to the study medication actually received ('as treated' population).
Arm/Group Title	Mircera		Placebo
Arm/Group Description	Methoxy polyethylene glycol-epoetin beta 30 mcg subcutaneous injection once monthly up to 24 months with sequential dose adjustments to 50 mcg or 75 mcg depending on change of hemoglobin values of more than 1.0 g/dL.		Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
All Cause Mortality
	Mircera		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Mircera		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/118 (35.6%)		48/117 (41%)
Blood and lymphatic system disorders
Normochromic normocytic anaemia	0/118 (0%)		1/117 (0.9%)
Anaemia	0/118 (0%)		1/117 (0.9%)
Cardiac disorders
Atrial flutter	0/118 (0%)		2/117 (1.7%)
Atrial fibrillation	1/118 (0.8%)		0/117 (0%)
Bundle branch block left	0/118 (0%)		1/117 (0.9%)
Myocardial infarction	2/118 (1.7%)		0/117 (0%)
Acute coronary syndrome	0/118 (0%)		1/117 (0.9%)
Acute myocardial infarction	1/118 (0.8%)		0/117 (0%)
Angina pectoris	0/118 (0%)		1/117 (0.9%)
Arrhythmia	1/118 (0.8%)		0/117 (0%)
Cardiac arrest	1/118 (0.8%)		0/117 (0%)
Cardiac failure congestive	0/118 (0%)		1/117 (0.9%)
Coronary artery disease	0/118 (0%)		1/117 (0.9%)
Coronary artery stenosis	0/118 (0%)		1/117 (0.9%)
Intracardiac thrombus	0/118 (0%)		1/117 (0.9%)
Congenital, familial and genetic disorders
Tibial torsion	0/118 (0%)		1/117 (0.9%)
Ear and labyrinth disorders
Vertigo	0/118 (0%)		1/117 (0.9%)
Endocrine disorders
Hyperthyroidism	1/118 (0.8%)		0/117 (0%)
Eye disorders
Ectropion	1/118 (0.8%)		0/117 (0%)
Lens dislocation	0/118 (0%)		1/117 (0.9%)
Vitreous haemorrhage	0/118 (0%)		1/117 (0.9%)
Gastrointestinal disorders
Diarrhoea	2/118 (1.7%)		3/117 (2.6%)
Constipation	1/118 (0.8%)		1/117 (0.9%)
Faecaloma	0/118 (0%)		2/117 (1.7%)
Abdominal hernia	0/118 (0%)		1/117 (0.9%)
Abdominal pain	0/118 (0%)		1/117 (0.9%)
Diabetic gastroparesis	0/118 (0%)		1/117 (0.9%)
Diverticular perforation	0/118 (0%)		1/117 (0.9%)
Gastritis	0/118 (0%)		1/117 (0.9%)
Reflux oesophagitis	0/118 (0%)		1/117 (0.9%)
Umbilical hernia	1/118 (0.8%)		0/117 (0%)
Vomiting	0/118 (0%)		1/117 (0.9%)
General disorders
Chest pain	1/118 (0.8%)		1/117 (0.9%)
Sudden death	1/118 (0.8%)		1/117 (0.9%)
General physical health deterioration	1/118 (0.8%)		0/117 (0%)
Multi-organ failure	0/118 (0%)		1/117 (0.9%)
Pain	1/118 (0.8%)		0/117 (0%)
Pyrexia	1/118 (0.8%)		0/117 (0%)
Hepatobiliary disorders
Bile duct stone	0/118 (0%)		2/117 (1.7%)
Liver disorder	1/118 (0.8%)		0/117 (0%)
Immune system disorders
Transplant rejection	1/118 (0.8%)		0/117 (0%)
Infections and infestations
Bronchopneumonia	1/118 (0.8%)		1/117 (0.9%)
Erysipelas	1/118 (0.8%)		1/117 (0.9%)
Gastroenteritis	2/118 (1.7%)		0/117 (0%)
Infection	1/118 (0.8%)		1/117 (0.9%)
Urinary tract infection	1/118 (0.8%)		1/117 (0.9%)
Urosepsis	2/118 (1.7%)		0/117 (0%)
Anal abscess	0/118 (0%)		1/117 (0.9%)
Diverticulitis	1/118 (0.8%)		0/117 (0%)
Febrile infection	1/118 (0.8%)		0/117 (0%)
Influenza	0/118 (0%)		1/117 (0.9%)
Kidney infection	1/118 (0.8%)		0/117 (0%)
Otitis externa	1/118 (0.8%)		0/117 (0%)
Pneumonia primary atypical	1/118 (0.8%)		0/117 (0%)
Pyelonephritis	1/118 (0.8%)		0/117 (0%)
Respiratory tract infection	1/118 (0.8%)		0/117 (0%)
Injury, poisoning and procedural complications
Humerus fracture	1/118 (0.8%)		1/117 (0.9%)
Ankle fracture	1/118 (0.8%)		0/117 (0%)
Meniscus lesion	0/118 (0%)		1/117 (0.9%)
Overdose	1/118 (0.8%)		0/117 (0%)
Rib fracture	0/118 (0%)		1/117 (0.9%)
Tendon rupture	1/118 (0.8%)		0/117 (0%)
Tibia fracture	1/118 (0.8%)		0/117 (0%)
Traumatic brain injury	1/118 (0.8%)		0/117 (0%)
Wrist fracture	1/118 (0.8%)		0/117 (0%)
Investigations
Haemoglobin decreased	2/118 (1.7%)		1/117 (0.9%)
Blood creatinine increased	1/118 (0.8%)		0/117 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	2/118 (1.7%)		1/117 (0.9%)
Hyperkalaemia	2/118 (1.7%)		0/117 (0%)
Hyponatraemia	0/118 (0%)		1/117 (0.9%)
Diabetes mellitus	0/118 (0%)		1/117 (0.9%)
Hypokalaemia	1/118 (0.8%)		0/117 (0%)
Lactic acidosis	1/118 (0.8%)		0/117 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/118 (0%)		1/117 (0.9%)
Back pain	0/118 (0%)		2/117 (1.7%)
Intervertebral disc protrusion	1/118 (0.8%)		1/117 (0.9%)
Osteoarthritis	2/118 (1.7%)		0/117 (0%)
Arthritis	1/118 (0.8%)		0/117 (0%)
Musculoskeletal pain	0/118 (0%)		1/117 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer	1/118 (0.8%)		0/117 (0%)
Adenocarcinoma	0/118 (0%)		1/117 (0.9%)
Basal cell carcinoma	0/118 (0%)		1/117 (0.9%)
Lip neoplasm malignant stage unspecified	0/118 (0%)		1/117 (0.9%)
Lipoma	0/118 (0%)		1/117 (0.9%)
Plasmacytoma	1/118 (0.8%)		0/117 (0%)
Prostate cancer	0/118 (0%)		1/117 (0.9%)
Squamous cell carcinoma	0/118 (0%)		1/117 (0.9%)
Nervous system disorders
Cerebrovascular accident	0/118 (0%)		2/117 (1.7%)
Cerebral haemorrhage	1/118 (0.8%)		0/117 (0%)
Cerebral ischaemia	0/118 (0%)		1/117 (0.9%)
Cerebrovascular disorder	1/118 (0.8%)		0/117 (0%)
Dizziness	1/118 (0.8%)		0/117 (0%)
Facial paresis	0/118 (0%)		1/117 (0.9%)
Hepatic encephalopathy	1/118 (0.8%)		0/117 (0%)
Myelopathy	1/118 (0.8%)		0/117 (0%)
Transient global amnesia	1/118 (0.8%)		0/117 (0%)
Renal and urinary disorders
Renal failure acute	1/118 (0.8%)		2/117 (1.7%)
Acute prerenal failure	0/118 (0%)		1/117 (0.9%)
Postrenal failure	1/118 (0.8%)		0/117 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/118 (0.8%)		0/117 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/118 (3.4%)		0/117 (0%)
Chronic obstructive pulmonary disease	0/118 (0%)		1/117 (0.9%)
Obstructive airways disorder	0/118 (0%)		1/117 (0.9%)
Pulmonary arterial hypertension	1/118 (0.8%)		0/117 (0%)
Pulmonary hypertension	1/118 (0.8%)		0/117 (0%)
Respiratory distress	1/118 (0.8%)		0/117 (0%)
Skin and subcutaneous tissue disorders
Rash	0/118 (0%)		1/117 (0.9%)
Skin ulcer	1/118 (0.8%)		0/117 (0%)
Surgical and medical procedures
Aortic anastomosis	0/118 (0%)		1/117 (0.9%)
Vascular disorders
Peripheral arterial occlusive disease	0/118 (0%)		3/117 (2.6%)
Hypertension	1/118 (0.8%)		1/117 (0.9%)
Hypertensive crisis	0/118 (0%)		1/117 (0.9%)
Other (Not Including Serious) Adverse Events
	Mircera		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	95/118 (80.5%)		99/117 (84.6%)
Gastrointestinal disorders
Diarrhoea	11/118 (9.3%)		13/117 (11.1%)
Nausea	0/118 (0%)		8/117 (6.8%)
General disorders
Oedema peripheral	11/118 (9.3%)		10/117 (8.5%)
Infections and infestations
Bronchitis	0/118 (0%)		9/117 (7.7%)
Influenza	9/118 (7.6%)		9/117 (7.7%)
Nasopharyngitis	29/118 (24.6%)		24/117 (20.5%)
Urinary tract infection	12/118 (10.2%)		7/117 (6%)
Musculoskeletal and connective tissue disorders
Back pain	0/118 (0%)		8/117 (6.8%)
Osteoarthritis	6/118 (5.1%)		0/117 (0%)
Pain in extremity	0/118 (0%)		6/117 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	13/118 (11%)		10/117 (8.5%)
Vascular disorders
Hypertension	11/118 (9.3%)		14/117 (12%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.