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A Study to Assess All-Cause Mortality and Cardiovascular Morbidity in Participants With Chronic Kidney Disease (CKD) on Dialysis and Those Not on Renal Replacement Therapy Receiving Methoxy Polyethylene Glycol-Epoetin Beta (Mircera) or Reference Erythropoietin Stimulating Agents (ESAs)

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ClinicalTrials.gov Identifier: NCT00773513
Recruitment Status : Completed
First Posted : October 16, 2008
Results First Posted : August 15, 2018
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE October 15, 2008
First Posted Date  ICMJE October 16, 2008
Results First Submitted Date  ICMJE July 18, 2018
Results First Posted Date  ICMJE August 15, 2018
Last Update Posted Date August 20, 2019
Actual Study Start Date  ICMJE December 12, 2008
Actual Primary Completion Date July 27, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
Time to Composite of All-Cause Mortality and Non-Fatal Cardiovascular Events (Myocardial Infarction, Stroke) Defined as Time Between First Dose of Study Medication and Date of Death or Non-Fatal Cardiovascular Events, Whichever Occurred First [ Time Frame: Baseline up to approximately 8.5 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 15, 2008)
Time to composite of all cause mortality and non-fatal cardiovascular events (myocardial infarctions, stroke). [ Time Frame: Event driven ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
  • Time to All-Cause Mortality [ Time Frame: Baseline up to approximately 8.5 years ]
  • Time to Non-Fatal and Fatal Myocardial Infarction [ Time Frame: Baseline up to approximately 8.5 years ]
  • Time to Non-Fatal and Fatal Stroke [ Time Frame: Baseline up to approximately 8.5 years ]
  • Time to Non-Fatal Cardiovascular Events (Myocardial Infarction or Stroke, Whichever Occurred First) [ Time Frame: Baseline up to approximately 8.5 years ]
  • Percentage of Participants With Anti-Erythropoietin Antibody-Mediated Pure Red Cell Aplasia (PRCA) [ Time Frame: Baseline up to approximately 8.5 years ]
  • Percentage of Participants With Gastrointestinal Bleeding [ Time Frame: Baseline up to approximately 8.5 years ]
  • Percentage of Participants With Thromboembolic Events [ Time Frame: Baseline up to approximately 8.5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2008)
  • Time to the individual components of the composite endpoint: time to death, time to non-fatal cardiovascular events (MI or stroke), time to MI and time to stroke. [ Time Frame: Event driven ]
  • Incidence of adverse events, and serious adverse events; vital signs, laboratory parameters, ECG. [ Time Frame: Throughout study ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess All-Cause Mortality and Cardiovascular Morbidity in Participants With Chronic Kidney Disease (CKD) on Dialysis and Those Not on Renal Replacement Therapy Receiving Methoxy Polyethylene Glycol-Epoetin Beta (Mircera) or Reference Erythropoietin Stimulating Agents (ESAs)
Official Title  ICMJE A Randomized, Controlled, Open-Label, Multi-Centre, Parallel-Group Study To Assess All-Cause Mortality And Cardiovascular Morbidity In Patients With Chronic Kidney Disease On Dialysis And Those Not On Renal Replacement Therapy Under Treatment With MIRCERA® Or Reference ESAs.
Brief Summary This 2 arm safety study will compare the outcome with respect to a composite endpoint of all-cause mortality and non-fatal cardiovascular events (myocardial infarction, stroke) in CKD participants either on dialysis or not receiving renal replacement therapy under treatment with methoxy polyethylene glycol-epoetin beta or reference ESAs. Participants will be randomized to receive intravenous (iv) or subcutaneous (sc) methoxy polyethylene glycol-epoetin beta at the following doses: for participants not already receiving ESA treatment, methoxy polyethylene glycol-epoetin beta will be administered at a starting dose of 0.6 micrograms per kilograms every 2 weeks (mcg/kg/2wks) iv or sc; for participants receiving maintenance ESA treatment, iv or sc methoxy polyethylene glycol-epoetin beta will be administered at an initial monthly dose of 120, 200 or 360 micrograms (mcg) depending on the weekly dose of ESA received prior to first methoxy polyethylene glycol-epoetin beta administration. Participants randomized to reference ESA treatment will receive iv or sc ESAs in accordance with their prescribed dosing information.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Renal Anemia
Intervention  ICMJE
  • Drug: Darbepoetin Alfa
    Darbepoetin alfa will be administered as per approved label.
    Other Name: Aranesp®, Nespo®, Aranest®
  • Drug: Epoetin Alfa
    Epoetin alfa will be administered as per approved label.
    Other Name: Eprex®, Epogen®, Epopen®, Erypo®
  • Drug: Epoetin Beta
    Epoetin beta will be administered as per approved label.
    Other Name: Neorecormon®, Recormon®
  • Drug: methoxy polyethylene glycol-epoetin beta
    Participants who are currently not being treated with an ESA will receive methoxy polyethylene glycol-epoetin beta administered at a starting dose of 0.6 mcg/kg body weight once every 2 weeks. Participants who are currently being treated with an ESA will receive methoxy polyethylene glycol-epoetin beta at a dose of 120, 200 or 360 mcg once monthly (based on ESA dose administered in Week -1)
    Other Name: Mircera®
Study Arms  ICMJE
  • Active Comparator: Erythropoiesis Stimulating Agents
    Participants will receive reference ESA according to approved label. The approved reference ESA compounds in the study will be darbepoetin alfa, epoetin alfa and epoetin beta.
    Interventions:
    • Drug: Darbepoetin Alfa
    • Drug: Epoetin Alfa
    • Drug: Epoetin Beta
    • Drug: methoxy polyethylene glycol-epoetin beta
  • Experimental: Methoxy Polyethylene Glycol-Epoetin Beta
    Participants not currently being treated with an ESA will receive methoxy polyethylene glycol-epoetin beta iv or sc once every 2 weeks for correction of renal anemia (target Hb 10-12 g/dL). Once corrected and in participants currently being treated with an ESA, methoxy polyethylene glycol-epoetin beta will be administered once monthly.
    Interventions:
    • Drug: Darbepoetin Alfa
    • Drug: Epoetin Alfa
    • Drug: methoxy polyethylene glycol-epoetin beta
Publications * Locatelli F, Hannedouche T, Fishbane S, Morgan Z, Oguey D, White WB. Cardiovascular Safety and All-Cause Mortality of Methoxy Polyethylene Glycol-Epoetin Beta and Other Erythropoiesis-Stimulating Agents in Anemia of CKD: A Randomized Noninferiority Trial. Clin J Am Soc Nephrol. 2019 Dec 6;14(12):1701-1710. doi: 10.2215/CJN.01380219. Epub 2019 Aug 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 20, 2018)
2825
Original Estimated Enrollment  ICMJE
 (submitted: October 15, 2008)
2800
Actual Study Completion Date  ICMJE July 27, 2017
Actual Primary Completion Date July 27, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female participants with symptomatic anemia associated with CKD
  • Participants with renal anemia who are not treated with an ESA:
  • Anemia was defined as hemoglobin (Hb) concentration less than (<) 11.0 grams per deciliter (g/dL) (mean of 2 screening values with at least one day and a maximum of 2 weeks between measurements) with clinical indication for ESA treatment
  • Participants with renal anemia who are on maintenance ESA therapy:
  • If on dialysis: regular long-term hemodialysis or peritoneal dialysis therapy with the same mode of dialysis for at least 3 months before screening
  • Hb concentration between 10 and 12 g/dL (mean of 2 screening values with at least one day and a maximum of 2 weeks between measurements)
  • Participants with adequate iron status defined as: serum ferritin above or equal to 100 micrograms per liter or transferrin saturation above or equal to 20 percent

Exclusion Criteria:

  • Contraindications to ESA treatment: uncontrolled hypertension, hypersensitivity to the active substance or any of the excipients, any other contraindication to ESA therapy
  • Conditions known to cause inadequate response to ESA treatment or anemia other than symptomatic anemia associated with CKD:
  • History of hemoglobinopathy
  • Anemia due to hemolysis
  • Pure red cell aplasia
  • High likelihood of early withdrawal (for example, within 1 year) or interruption of the study
  • Pregnancy or breast-feeding
  • Women of childbearing potential without effective contraception
  • Administration of another investigational drug within 1 month before screening or planned during the study period
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Croatia,   Czechia,   France,   Germany,   Greece,   Israel,   Italy,   Korea, Republic of,   Lithuania,   Malaysia,   Mexico,   Panama,   Philippines,   Poland,   Russian Federation,   Serbia,   Singapore,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   United Kingdom
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT00773513
Other Study ID Numbers  ICMJE BH21260
2007-005129-31
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Hoffmann-La Roche
Original Responsible Party Clinical Trials, Study Director, Hoffmann-La Roche
Current Study Sponsor  ICMJE Hoffmann-La Roche
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP