Kidney Disease, ChronicPhase 2NCT01194154
A Study of Methoxy Polyethylene Glycol-epoetin Beta (Mircera) in Participants With Chronic Kidney Disease (PRIMAVERA)
A Phase 2 study testing Methoxy polyethylene glycol-epoetin beta in people with Kidney Disease, Chronic, run by Hoffmann-La Roche at 33 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Disease, Chronic
- What is being tested?
- Methoxy polyethylene glycol-epoetin beta
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 241 participants
- Where
- 33 sitesGermany
- Study dates
- 30 Sep 2010to 31 Mar 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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%
Trial locations and contacts
33 sites in 1 country.
33 sites in 1 country
Germany33 sites
Uniklinik RWTH Aachen; Med. Klinik II; Klinik für Nephrologie und klinische Immunologie
Aachen, 52057
Dialysepraxis Dr. Stallforth, Dr. Kirschner, Dr. Al-Sarraf und Dr. Pawlik
Augsburg, 86157
KfH Kuratorium für Dialyse und Nierentransplantation e.V. im Kurhaus
Bad König, 64732
Charité - Klinikum Mitte; Medizinische Klinik Für Nephrologie
Berlin, 10117
Charité - Campus Benjamin Franklin; Zentrum fuer Innere Medizin, Med. Klinik I
Berlin, 12203
Gemeinschaftspraxis Dres. Erika Eger, Frank Seibt, Oliver Eike u.w. - Dialysezentrum Treptower Park
Berlin, 12435
Dialyse-Institut Bovenden
Bovenden, 37120
Kliniken der Stadt Köln gGmbH Krankenhaus Merheim
Cologne, 51109
Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
Dresden, 01307
DaVita Clinical Research Deutschland GmbH
Düsseldorf, 40210
Universitätsklinikum Essen Zentrum f.Innere Medizin Abt.Nephrologie
Essen, 45122
Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik III
Frankfurt, 60596
Uniklinikum Heidelberg
Heidelberg, 69120
Dialysepraxis Prof.Dr.med. Michael Rambausek Dres. Stephan Matthias und Gabriele Kunowski - Dialysz.
Heilbronn, 74076
Nephrologisches Zentrum Hilden am St. Josefs-Krankenhaus
Hilden, 40724
Universitaetsklinikum des Saarlandes; Klinik f. Innere Medizin IV
Homburg/Saar, 66424
Dres. Jan Nawka und Frank Pistrosch
Hoyerswerda, 02977
Westpfalz-Klinikum Gmbh; Nephrologie/Transplantationsmedizin
Kaiserslautern, 67655
PHV Patienten-Heimversorgung Dialyse-Station
Kiel, 24106
Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Transplantationszentrum
Lübeck, 23562
Gemienschaftspraxis Dres. Leistikow, Rachti & Sandner
Mannheim, 68309
Dres. Michael Koch Hannelore Klimke Wolfgang Kulas u.w.
Mettmann, 40822
Klinikum Innenstadt Medizinische Klinik; Abt.Endokrinologie und Diabetologie
München, 80336
Klinikum d.Universität München Campus Großhadern
München, 81377
Nierenzentrum Bogenhausen/Perlach; Praxis für Nierenheilkunde
München-Bogenhausen, 81925
Universitätsklinikum Münster Innere Medizin D
Münster, 48149
Dres. Georg Fuchs und Nexhat Miftari
Neckarsulm, 74172
Nephrologische Praxis Neunkirchen - Dr.med. Klemens Dorr und Artem Goldmann
Neunkirchen/Saar, 66538
Dialysezentrum Saarlouis
Saarlouis, 66740
Gemeinschaftspraxis Rosemarie Krämer und Lars Rothermund
Ulm, 89077
Nephrologisches Zentrum
Velbert, 42549
Nephrologisches Zentrum Dialyse-Institut
Villingen-Schwenningen, 78052
KfH Kuratiorium für Dialyse und Nierentransplantation e.V.
Wiesbaden, 65191
About this study
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)
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.
- Conditions
- Kidney Disease, Chronic
- Being tested
- Methoxy polyethylene glycol-epoetin beta, Placebo
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methoxy polyethylene glycol-epoetin betaDrug
Also called Mircera, C.E.R.A.
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).
PlaceboDrug
Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months.
| Study group | Role | What they receive |
|---|---|---|
| Mircera | Experimental | Not described Receives: Drug: Methoxy polyethylene glycol-epoetin beta |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (6)
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.
Measured: 24 months
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.
Measured: Baseline, Month 24
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.
Measured: Baseline, Month 24
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.
Measured: Baseline, Month 24
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.
Measured: Baseline, Month 24
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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2010 (estimated)
- Study start30 Sep 2010
- Primary completion31 Mar 2015
- Study completion31 Mar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney Disease, ChronicStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 241 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01194154
- Sponsor's protocol ID
- ML22916
- Other IDs
- 2009-015114-22, 2009
- Status last verified
- Apr 2017
- First submitted
- 25 Aug 2010
- Last updated
- 10 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Chung EY, Palmer SC, Saglimbene VM, Craig JC, Tonelli M, Strippoli GF. Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis. Cochrane Database Syst Rev. 2023 Feb 13;2(2):CD010590. doi: 10.1002/14651858.CD010590.pub3.
PubMed 36791280
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01194154
- Acronym / sponsor ID
- ML22916
- Conditions
- Kidney Disease, Chronic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 241 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 30 Sep 2010 (actual)
- Primary completion
- 31 Mar 2015 (actual)
- Study completion
- 31 Mar 2015 (actual)
- First posted
- 2 Sep 2010 (estimated)
- Results
- Posted 14 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mircera | Experimental | Drug: Methoxy polyethylene glycol-epoetin beta |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methoxy polyethylene glycol-epoetin betaAlso: Mircera, C.E.R.A.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). | Drug | Mircera |
| PlaceboPlacebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months. | Drug | Placebo |
Primary outcome
Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Modification of Diet in Renal Disease With 4 Variables (MDRD-4)
Time frame: 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.
6 secondary outcomes
Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Time frame: 24 months
Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Month 24
Time frame: Baseline, Month 24
Change From Baseline in Serum Creatinine Concentration at Month 24
Time frame: Baseline, Month 24
Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Month 24
Time frame: Baseline, Month 24
Change From Baseline in Serum Cystatin C Concentration at Month 24
Time frame: Baseline, Month 24
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36791280Chung EY, Palmer SC, Saglimbene VM, Craig JC, Tonelli M, Strippoli GF. Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis. Cochrane Database Syst Rev. 2023 Feb 13;2(2):CD010590. doi: 10.1002/14651858.CD010590.pub3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
33 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methoxy polyethylene glycol-epoetin beta in people with Kidney Disease, Chronic, run by Hoffmann-La Roche at 33 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Yearly Reduction Rate of Estimated Glomerular Filtration Rate (eGFR) Calculated by Modification of Diet in Renal Disease With 4 Variables (MDRD-4) (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01194154, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2017.