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LATINO Study: A Study of Mircera for the Maintenance Treatment of Dialysis Patients With Chronic Renal Anemia.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00517413
First received: August 16, 2007
Last updated: March 29, 2016
Last verified: March 2016
  Purpose
This single arm study will assess the efficacy and safety of Mircera when administered once monthly, subcutaneously or intravenously, for the maintenance of hemoglobin levels in dialysis patients with chronic renal anemia. Patients currently receiving maintenance treatment with epoetin alfa will receive monthly injections of Mircera with a starting dose (120, 200 or 360 micrograms) derived from the dose of epoetin alfa they were receiving in the week preceding study start. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Condition Intervention Phase
Anemia
Drug: methoxy polyethylene glycol-epoetin beta [Mircera]
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-Arm Open-Label Study to Assess the Efficacy, Safety, and Tolerability of Once-Monthly Administration of Intravenous and/or Subcutaneous C.E.R.A for the Maintenance of Hemoglobin Levels in Dialysis Patients With Chronic Renal Anemia

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants Maintaining Their Mean Hb Concentration Within ±1.0 Gram/Deciliter of Their Reference Hb and Between 10.5 and 12.5 Gram/Deciliter [ Time Frame: EEP (Week 16 to 24) ] [ Designated as safety issue: No ]
    The haemoglobin (Hb) levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The reference Hb value was defined on the basis of individual participant's all assessments at Weeks -4, -3, -2, -1 and 0. The Hb value on the first day of first dose (Week 0) was included in the calculation, as this assessment was performed before the first dose was given. The percentage of participants maintaining their mean Hb concentration within +/-1.0 gram/deciliter (g/dL) of their reference Hb and between 10.5 and 12.5 g/dL are reported for efficacy evaluation period (EEP). Efficacy evaluation period was from Week 16 to Week 24 after completion of 16-week dose titration period (DTP).


Secondary Outcome Measures:
  • Mean Change in the Hb Concentration Between the Stability Verification Period and the EEP [ Time Frame: SVP (Week -4 to -1), EEP (Week 16 to 24) ] [ Designated as safety issue: No ]
    The Hb levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The mean change in the Hb concentration between the Stability Verification Period (SVP) and the EEP is reported.

  • Percentage of Participants Maintaining Hb Concentration Within The Target Range 10.5 and 12.5 g/dL Throughout the EEP [ Time Frame: EEP (Week 16 to 24) ] [ Designated as safety issue: No ]
    The Hb levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The percentage of participants maintaining their mean Hb concentration within the target range 10.5 and 12.5 g/dL throughout the EEP are reported.

  • Mean Time Spent by the Participants in the Hb Target Range 10.5-12.5 g/dL During EEP [ Time Frame: EEP (Week 16 to 24) ] [ Designated as safety issue: No ]
    The Hb levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The mean time (days) spent by the participants in the Hb target range 10.5 to 12.5 is reported.

  • Mean C.E.R.A Dose To Maintain Hb Level Within the Range 10.5-12.5 g/dL Throughout the EEP [ Time Frame: EEP (Week 16 to 24) ] [ Designated as safety issue: No ]
    The Hb levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The mean C.E.R.A dose required to maintain the Hb level within the range 10.5-12.5 g/dL throughout the EEP is presented.

  • Percentage of Participants Requiring Dose Adjustments of C.E.R.A During the DTP and EEP [ Time Frame: Baseline (Week 0) to Week 24 ] [ Designated as safety issue: No ]
    Dose adjustments were necessary when Hb increased or decreased by a clinically significant amount. The dose of C.E.R.A. was adjusted to maintain the individual participant's Hb within a range of +/-1.0 g/dL of the reference Hb concentration and between 10.5 and 12.5 g/dL throughout the DTP (Week 0 to Week 16) and the EEP (Weeks 16 to 24). The reference Hb value was taken as the mean of all Hb assessments during the stability verification period (Weeks -4, -3, -2, -1). The percentage of participants requiring C.E.R.A dose adjustments during the DTP and EEP are presented.

  • Mean Monthly Dose of C.E.R.A During the DTP and EEP [ Time Frame: Baseline (Week 0) to Week 24 ] [ Designated as safety issue: No ]
    The initial dose of C.E.R.A. was 120, 200, or 360 mcg IV or SC every 4 weeks for 48 weeks, which was based on the last dose of the previous ESA. Dose adjustments were necessary when Hb increased or decreased by a clinically significant amount. The dose of C.E.R.A. was adjusted to maintain the individual participant's Hb within a range of +/-1.0 g/dL of the reference Hb concentration and between 10.5 and 12.5 g/dL throughout the DTP and the EEP. The reference Hb value was taken as the mean of all Hb assessments during the stability verification period. The mean monthly doses of C.E.R.A during the DTP and EEP are presented.

  • Incidence of Red Blood Cell Transfusions During the C.E.R.A. Treatment Phase [ Time Frame: Baseline (Week 0) to Week 44 ] [ Designated as safety issue: No ]
    Red blood cell (RBC) transfusions were permitted during the treatment period in case of medical need. The pre-transfusion Hb level was measured before any transfusion was administered.

  • Number of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    Adverse event (AE) and Serious adverse event (SAE) data was reported for the safety population which included all participants who entered into the study.

  • Mean Haemoglobin Levels Over Time [ Time Frame: Baseline (Week 0), Week 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 ] [ Designated as safety issue: No ]
    The Hb levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference range for Hb are as follows: Female: min-max for lower limit=11 to 13 g/dL and min-max for upper limit=14 to 18.1 g/dL; Male: min-max for lower limit=12 to 14.2 g/dL and min-max for upper limit=16 to 18.1 g/dL.

  • Mean Hematocrit Levels Over Time [ Time Frame: Baseline (Week 0), Week 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 ] [ Designated as safety issue: No ]
    The haematocrit (HCT) levels in fraction were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference range for hematocrit are as follows: Female: min-max for lower limit=0.12 - 0.38 and min-max of upper limit=0.43 - 0.537; Male: min-max for lower limit=0.35 - 0.45 and min-max of upper limit=0.45 - 0.54.

  • Mean White Blood Cells and Thrombocyte Levels Over Time [ Time Frame: Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    The white blood cells (WBC) and thrombocyte levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for WBC are as follows: Female/Male: min-max for lower limit= 3.5 - 5*10^9 cells/L and min-max of upper limit= 9 -13.5*10^9 cells/L. The standard reference ranges for thrombocyte are as follows: Female/Male: min-max for lower limit= 130 - 150*10^9 cells/L and min-max of upper limit= 300 - 450*10^9 cells/L.

  • Mean Phosphate and Potassium Levels Over Time [ Time Frame: Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    The phosphate and potassium levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for phosphate are as follows: Female/Male: min-max for lower limit= 0.48435 - 0.9687 mmol/L and min-max for upper limit=1.45305 - 2.2603 mmol/L. The standard reference ranges for potassium are as follows: Female/Male: min-max for lower limit=3.1 - 3.7 mmol/L and min-max for upper limit=5 - 5.5 mmol/L.

  • Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time [ Time Frame: Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    The creatinine, iron, and total iron binding capacity (TIBC) levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for creatinine are as follows: Female: min-max for lower limit=0 - 70.72 mmol/L and min-max for upper limit=79.56 - 123.76 mmol/L; Male: min-max for lower limit=0 - 70.72 mmol/L and min-max for upper limit=97.24 - 123.76 mmol/L. The standard reference ranges for iron are as follows: Female: min-max for lower limit=6.265 - 10.74 mmol/L and min-max for upper limit=25.06 - 32.22 mmol/L and Male: min-max for lower limit=6.265 - 11.635 mmol/L and min-max for upper limit=25.06 - 32.22 mmol/L. The standard reference ranges for TIBC are as follows: Female: min-max for lower limit=19.69 - 49.046 mmol/L and min-max for upper limit=62.65 - 88.963 mmol/L and Male: min-max for lower limit=19.69 - 52.089 mmol/L and min-max for upper limit=62.65 - 80.55 mmol/L.

  • Mean Transferrin Saturation Levels Over Time [ Time Frame: Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    Transferrin saturation (TSAT) is the ratio of serum iron and total iron-binding capacity. Transferrin is a blood protein that picks up iron absorbed by the intestines and transports it from one location to another. When iron absorption is abnormally high, transferrin proteins become more saturated with iron. An elevated TS value therefore reflects an increase in iron absorption. The TSAT levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. TSAT was calculated automatically in the electronic case report form (eCRF) according to the following formulae: TSAT= (Serum Iron*100)/(Transferrin*1.41) or TSAT=(Serum Iron*100)/TIBC. Calculated data was not provided by laboratory; therefore no reference range is available.

  • Mean Albumin and Transferrin Levels Over Time [ Time Frame: Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    The albumin and transferrin levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for albumin are as follows: Female/Male: min-max for lower limit=30 - 35 g/L and min-max for upper limit=48 - 55 g/L. The standard reference ranges for transferrin are as follows: Female/Male: min-max for lower limit=1.5 - 2.3 g/L and min-max for upper limit=2.87 - 4.3 g/L.

  • Mean C-Reactive Protein Levels Over Time [ Time Frame: Baseline (Week 0), 8, 16, 24, 32, 40, and 48 ] [ Designated as safety issue: No ]
    C-reactive protein (CRP) is produced by the liver. The level of CRP rises when there is inflammation throughout the body. The CRP test is a general test to check for inflammation in the body.The CRP levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for CRP are as follows: Female/Male: min-max for lower limit=0 - 10 mg/L and min-max for upper limit=0.5 - 30 mg/L.

  • Mean Ferritin Levels Over Time [ Time Frame: Baseline (Week 0), Week 8, 16, 24, 32, 40, and 48 ] [ Designated as safety issue: Yes ]
    Ferritin is a protein found inside cells that stores iron so that the body can use it later. A ferritin test indirectly measures the amount of iron in your blood. The Ferritin levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The standard reference ranges for ferritin are as follows: Female: min-max for lower limit=6 - 50 mcg/L and min-max for upper limit=120 - 400 mcg/L; Male: min-max for lower limit=10 - 50 mcg/L and min-max for upper limit=200 - 400 mcg/L.


Enrollment: 163
Study Start Date: October 2007
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: C.E.R.A
Participants with chronic renal anaemia who were on dialysis and previously treated with intravenous (IV) or subcutaneous (SC) epoetin alfa, epoetin beta or darbepoetin alfa received monthly treatment with Continuous Erythropoietin Receptor Activator (C.E.R.A.) (methoxy polyethylene glycol-epoetin beta [Mircera]). The initial dose of C.E.R.A. was based on the last dose of the previous Erythropoiesis Stimulating Agent (ESA); 120, 200, or 360 micrograms (mcg) C.E.R.A., IV or SC, every 4 weeks for 48 weeks.
Drug: methoxy polyethylene glycol-epoetin beta [Mircera]
120, 200 or 360 micrograms sc or iv monthly, starting dose

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • chronic renal anemia;
  • hemodialysis or peritoneal dialysis, with same mode of dialysis for >=3 months before and throughout screening period;
  • stable maintenance epoetin alfa therapy for past 2 months.

Exclusion Criteria:

  • transfusion of red blood cells during previous 2 months;
  • poorly controlled hypertension requiring interruption of epoetin alfa in past 6 months;
  • acute or chronic bleeding during previous 2 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00517413

Locations
Argentina
Buenos Aires, Argentina, 1155
Buenos Aires, Argentina, 1437
Buenos Aires, Argentina, 1663
Buenos Aires, Argentina, 1824
Córdoba, Argentina, 5000
Santa Fe, Argentina, 3000
Brazil
Aracajú, Brazil, 49055-210
Curitiba, Brazil, 80050-350
Fortaleza, Brazil, 60430-370
Sao Paulo, Brazil, 05624-000
Chile
Santiago, Chile, 056
Colombia
Bogota, Colombia, 0
Bogotá, Colombia
Ecuador
Quito, Ecuador, 2569
Mexico
Cuernavaca, Mexico, 62448
Mexico City, Mexico, 03900
Mexico City, Mexico, 11520
Mexico City, Mexico, 14000
Mexico City, Mexico, 14050
Monterrey, Mexico, 64710
Peru
Callao, Peru, C 01
Callao, Peru, C01
Lima, Peru, L13
Uruguay
Montevideo, Uruguay, 11600
Montevideo, Uruguay, 11800
Venezuela
Caracas, Venezuela, 1060
Caracas, Venezuela, 1062
Maracaibo, Venezuela, 4002
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00517413     History of Changes
Other Study ID Numbers: ML20881 
Study First Received: August 16, 2007
Results First Received: February 24, 2016
Last Updated: March 29, 2016
Health Authority: Ecuador: Ministry of Health

Additional relevant MeSH terms:
Anemia
Hematologic Diseases
Epoetin Alfa
Hematinics

ClinicalTrials.gov processed this record on December 08, 2016