Back to resultsA Study of Methoxy Polyethylene Glycol-epoetin Beta (Mircera) in Participants With Chronic Kidney Disease (PRIMAVERA)
Primary Purpose
Kidney Disease, Chronic
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Methoxy polyethylene glycol-epoetin beta
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Kidney Disease, Chronic
Eligibility Criteria
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%
Sites / Locations
- Uniklinik RWTH Aachen; Med. Klinik II; Klinik für Nephrologie und klinische Immunologie
- Dialysepraxis Dr. Stallforth, Dr. Kirschner, Dr. Al-Sarraf und Dr. Pawlik
- KfH Kuratorium für Dialyse und Nierentransplantation e.V. im Kurhaus
- Charité - Klinikum Mitte; Medizinische Klinik Für Nephrologie
- Charité - Campus Benjamin Franklin; Zentrum fuer Innere Medizin, Med. Klinik I
- Gemeinschaftspraxis Dres. Erika Eger, Frank Seibt, Oliver Eike u.w. - Dialysezentrum Treptower Park
- Dialyse-Institut Bovenden
- Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
- DaVita Clinical Research Deutschland GmbH
- Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie
- Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III
- Uniklinikum Heidelberg
- Dialysepraxis Prof.Dr.med. Michael Rambausek Dres. Stephan Matthias und Gabriele Kunowski - Dialysz.
- Nephrologisches Zentrum Hilden am St. Josefs-Krankenhaus
- Universitaetsklinikum des Saarlandes; Klinik f. Innere Medizin IV
- Dres. Jan Nawka und Frank Pistrosch
- Westpfalz-Klinikum Gmbh; Nephrologie/Transplantationsmedizin
- PHV Patienten-Heimversorgung Dialyse-Station
- Kliniken der Stadt Köln gGmbH Krankenhaus Merheim
- Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Transplantationszentrum
- Gemienschaftspraxis Dres. Leistikow, Rachti & Sandner
- Dres. Michael Koch Hannelore Klimke Wolfgang Kulas u.w.
- Klinikum Innenstadt Medizinische Klinik; Abt.Endokrinologie und Diabetologie
- Nierenzentrum Bogenhausen/Perlach; Praxis für Nierenheilkunde
- Klinikum d.Universität München Campus Großhadern
- Universitätsklinikum Münster Innere Medizin D
- Dres. Georg Fuchs und Nexhat Miftari
- Nephrologische Praxis Neunkirchen - Dr.med. Klemens Dorr und Artem Goldmann
- Dialysezentrum Saarlouis
- Gemeinschaftspraxis Rosemarie Krämer und Lars Rothermund
- Nephrologisches Zentrum
- Nephrologisches Zentrum Dialyse-Institut
- KfH Kuratiorium für Dialyse und Nierentransplantation e.V.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Mircera
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Modification of Diet in Renal Disease With 4 Variables (MDRD-4)
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
Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
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.
Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 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.
Change From Baseline in Serum Creatinine Concentration at 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.
Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at 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.
Change From Baseline in Serum Cystatin C Concentration at 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.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01194154
Brief Title
A Study of Methoxy Polyethylene Glycol-epoetin Beta (Mircera) in Participants With Chronic Kidney Disease (PRIMAVERA)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
September 30, 2010 (Actual)
Primary Completion Date
March 31, 2015 (Actual)
Study Completion Date
March 31, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Disease, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
241 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mircera
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Methoxy polyethylene glycol-epoetin beta
Other Intervention Name(s)
Mircera, C.E.R.A.
Intervention 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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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%
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Uniklinik RWTH Aachen; Med. Klinik II; Klinik für Nephrologie und klinische Immunologie
City
Aachen
ZIP/Postal Code
52057
Country
Germany
Facility Name
Dialysepraxis Dr. Stallforth, Dr. Kirschner, Dr. Al-Sarraf und Dr. Pawlik
City
Augsburg
ZIP/Postal Code
86157
Country
Germany
Facility Name
KfH Kuratorium für Dialyse und Nierentransplantation e.V. im Kurhaus
City
Bad König
ZIP/Postal Code
64732
Country
Germany
Facility Name
Charité - Klinikum Mitte; Medizinische Klinik Für Nephrologie
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Charité - Campus Benjamin Franklin; Zentrum fuer Innere Medizin, Med. Klinik I
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Gemeinschaftspraxis Dres. Erika Eger, Frank Seibt, Oliver Eike u.w. - Dialysezentrum Treptower Park
City
Berlin
ZIP/Postal Code
12435
Country
Germany
Facility Name
Dialyse-Institut Bovenden
City
Bovenden
ZIP/Postal Code
37120
Country
Germany
Facility Name
Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
DaVita Clinical Research Deutschland GmbH
City
Düsseldorf
ZIP/Postal Code
40210
Country
Germany
Facility Name
Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Facility Name
Uniklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Dialysepraxis Prof.Dr.med. Michael Rambausek Dres. Stephan Matthias und Gabriele Kunowski - Dialysz.
City
Heilbronn
ZIP/Postal Code
74076
Country
Germany
Facility Name
Nephrologisches Zentrum Hilden am St. Josefs-Krankenhaus
City
Hilden
ZIP/Postal Code
40724
Country
Germany
Facility Name
Universitaetsklinikum des Saarlandes; Klinik f. Innere Medizin IV
City
Homburg/Saar
ZIP/Postal Code
66424
Country
Germany
Facility Name
Dres. Jan Nawka und Frank Pistrosch
City
Hoyerswerda
ZIP/Postal Code
02977
Country
Germany
Facility Name
Westpfalz-Klinikum Gmbh; Nephrologie/Transplantationsmedizin
City
Kaiserslautern
ZIP/Postal Code
67655
Country
Germany
Facility Name
PHV Patienten-Heimversorgung Dialyse-Station
City
Kiel
ZIP/Postal Code
24106
Country
Germany
Facility Name
Kliniken der Stadt Köln gGmbH Krankenhaus Merheim
City
Köln
ZIP/Postal Code
51109
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Transplantationszentrum
City
Lübeck
ZIP/Postal Code
23562
Country
Germany
Facility Name
Gemienschaftspraxis Dres. Leistikow, Rachti & Sandner
City
Mannheim
ZIP/Postal Code
68309
Country
Germany
Facility Name
Dres. Michael Koch Hannelore Klimke Wolfgang Kulas u.w.
City
Mettmann
ZIP/Postal Code
40822
Country
Germany
Facility Name
Klinikum Innenstadt Medizinische Klinik; Abt.Endokrinologie und Diabetologie
City
Muenchen
ZIP/Postal Code
80336
Country
Germany
Facility Name
Nierenzentrum Bogenhausen/Perlach; Praxis für Nierenheilkunde
City
München-Bogenhausen
ZIP/Postal Code
81925
Country
Germany
Facility Name
Klinikum d.Universität München Campus Großhadern
City
München
ZIP/Postal Code
81377
Country
Germany
Facility Name
Universitätsklinikum Münster Innere Medizin D
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Dres. Georg Fuchs und Nexhat Miftari
City
Neckarsulm
ZIP/Postal Code
74172
Country
Germany
Facility Name
Nephrologische Praxis Neunkirchen - Dr.med. Klemens Dorr und Artem Goldmann
City
Neunkirchen/Saar
ZIP/Postal Code
66538
Country
Germany
Facility Name
Dialysezentrum Saarlouis
City
Saarlouis
ZIP/Postal Code
66740
Country
Germany
Facility Name
Gemeinschaftspraxis Rosemarie Krämer und Lars Rothermund
City
Ulm
ZIP/Postal Code
89077
Country
Germany
Facility Name
Nephrologisches Zentrum
City
Velbert
ZIP/Postal Code
42549
Country
Germany
Facility Name
Nephrologisches Zentrum Dialyse-Institut
City
Villingen-Schwenningen
ZIP/Postal Code
78052
Country
Germany
Facility Name
KfH Kuratiorium für Dialyse und Nierentransplantation e.V.
City
Wiesbaden
ZIP/Postal Code
65191
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
A Study of Methoxy Polyethylene Glycol-epoetin Beta (Mircera) in Participants With Chronic Kidney Disease (PRIMAVERA)
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