A Study of Monthly Subcutaneous (SC) Mircera for Maintenance Treatment of Participants With Chronic Kidney Disease on Peritoneal Dialysis (MISTRAL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00737477
First received: August 18, 2008
Last updated: June 17, 2016
Last verified: June 2016
  Purpose
This single-arm study will assess the efficacy and safety of monthly administration of SC Mircera for the maintenance of hemoglobin levels in participants with chronic kidney disease on peritoneal dialysis. Participants currently receiving maintenance treatment with SC erythropoietin stimulating agents (ESAs) will receive monthly SC injections of Mircera, with the starting dose derived from the last weekly ESA they had been receiving.

Condition Intervention Phase
Anemia
Drug: Methoxy polyethylene glycol-epoetin beta
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, Multicentre Study to Assess the Maintenance of Haemoglobin Levels With Once Monthly Subcutaneous Administration of C.E.R.A (Continuous Erythropoietin Receptor Activator) in Patients With Chronic Kidney Disease on Peritoneal Dialysis

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants Who Maintained Average Hb Value Within Target Range During the EEP [ Time Frame: Weeks 16 to 24 ] [ Designated as safety issue: No ]
    Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP (Weeks 16 to 24) was calculated per participant and assessed against the target range. The percentage of participants who had average Hb during the EEP in the target range (10 to 12 g/dL) was determined as the primary endpoint. The 95 percent (%) confidence interval (CI) was calculated using the Pearson-Clopper method for exact confidence bounds.


Secondary Outcome Measures:
  • Percentage of Participants With Hb Values Within Target Range During the EEP [ Time Frame: Weeks 16 to 24 ] [ Designated as safety issue: No ]
    During the EEP (Weeks 16 to 24), participants provided a total of three pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The percentage of participants who had at least one, two, or all three Hb values during the EEP in the target range (10 to 12 g/dL) was determined.

  • Change in Hb Value From Baseline to the EEP [ Time Frame: Baseline and Weeks 16 to 24 ] [ Designated as safety issue: No ]
    Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment screening period (Weeks -4 to 0). Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP (Weeks 16 to 24) was calculated per participant and assessed against the reference value. The mean change in Hb value between reference (i.e., "Baseline") Hb and the EEP average Hb was calculated and expressed in g/dL.

  • Time Spent in the Target Range for Hb During the EEP and the Overall Treatment Period [ Time Frame: Weeks 16 to 24 and Weeks 0 to 48 ] [ Designated as safety issue: No ]
    Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Time spent in the target range (10 to 12 g/dL) was defined as time from first on-target Hb measurement to time of last known on-target Hb measurement, as collected during the EEP (Weeks 16 to 24) and the overall treatment period (Weeks 0 to 48). Time spent in the target range was averaged among all participants and expressed in weeks.

  • Percentage of Participants With Hb Value Within Plus/Minus (±) 1 g/dL of Reference Hb and Within the Target Range by Study Visit [ Time Frame: Baseline and Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48 ] [ Designated as safety issue: No ]
    Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment screening period (Weeks -4 to 0). Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The percentage of participants who had average Hb during the EEP (Weeks 16 to 24) and follow-up (Weeks 28 to 48) in the target range (10 to 12 g/dL) and within ±1 g/dL of their individual reference Hb was determined by study visit.

  • Percentage of Participants With Cycles or Excursions [ Time Frame: Weeks 4 to 44 ] [ Designated as safety issue: No ]
    Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Cycles were defined as a change in Hb greater than (>) 1.5 g/dL lasting longer than 8 weeks. Excursions were defined as half of one full cycle, or an increase ("up" excursions) or decrease ("down" excursions) >1.5 g/dL lasting longer than 4 weeks according to Hb measurements collected during the study. The percentage of participants with at least one cycle or excursion during Weeks 4 to 44 was calculated.

  • Percentage of Participants With Up Excursions [ Time Frame: Weeks 4 to 16, Weeks 16 to 24, Weeks 24 to 44 ] [ Designated as safety issue: No ]
    Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA during the DAP, EEP, and follow-up. Excursions were defined as half of one full cycle, or an increase ("up" excursions) or decrease ("down" excursions) in Hb >1.5 g/dL lasting longer than 4 weeks. The percentage of participants with at least one up excursion was calculated for Weeks 4 to 16, Weeks 16 to 24, and Weeks 24 to 44.

  • Percentage of Participants With Down Excursions [ Time Frame: Weeks 4 to 16, Weeks 16 to 24, Weeks 24 to 44 ] [ Designated as safety issue: No ]
    Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA during the DAP, EEP, and follow-up. Excursions were defined as half of one full cycle, or an increase ("up" excursions) or decrease ("down" excursions) in Hb >1.5 g/dL lasting longer than 4 weeks. The percentage of participants with at least one down excursion was calculated for Weeks 4 to 16, Weeks 16 to 24, and Weeks 24 to 44.

  • Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA [ Time Frame: Weeks 4 to 20, Weeks 24 to 48, Weeks 4 to 48 ] [ Designated as safety issue: No ]
    Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The percentage of participants who required any dose adjustment (including decreased dose, increased dose, and dose not performed) was calculated for Weeks 4 to 20, Weeks 24 to 48, and Weeks 4 to 48.

  • Number of Dose Adjustments of Mircera/CERA [ Time Frame: Weeks 4 to 20, Weeks 24 to 48, Weeks 4 to 48 ] [ Designated as safety issue: No ]
    Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The number of dose adjustments performed for each participant was averaged among all participants for Weeks 4 to 20, Weeks 24 to 48, and Weeks 4 to 48.

  • Absolute Change in Dose of Mircera/CERA by Study Week [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 ] [ Designated as safety issue: No ]
    Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The absolute difference in dose from the previous week was calculated at each visit and averaged among all participants.

  • Percent Change in Dose of Mircera/CERA by Study Week [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 ] [ Designated as safety issue: No ]
    Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The percent difference in dose from the previous week was calculated at each visit as [(current dose minus previous week dose) divided by previous week dose] multiplied by 100, and averaged among all participants.

  • Percentage of Participants Requiring Blood Transfusions [ Time Frame: Weeks 0 to 48 ] [ Designated as safety issue: No ]
    The percentage of participants who received at least one red blood cell transfusion during the overall treatment period (Weeks 0 to 48) was calculated.


Enrollment: 96
Study Start Date: September 2008
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mircera in Renal Anemia
Participants will receive SC methoxy polyethylene glycol-epoetin beta (Mircera) every 4 weeks for a total of 48 weeks in this single-arm study. The first dose of 120 or 200 micrograms (mcg) will be determined by the dose of ESA received prior to administration of study treatment, while subsequent doses will be adjusted to maintain hemoglobin within the target range.
Drug: Methoxy polyethylene glycol-epoetin beta
Mircera will be administered SC every 4 weeks for a total of 48 weeks. The first dose of 120 or 200 mcg will be determined by the dose of ESA received prior to administration of study treatment, while subsequent doses will be adjusted to maintain hemoglobin within the target range.
Other Names:
  • Mircera
  • CERA

  Eligibility

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

Inclusion Criteria:

  • Adults greater than or equal to (≥) 18 years of age
  • Chronic kidney disease-related anemia on peritoneal dialysis for ≥3 months
  • Continuous SC maintenance stable ESA therapy for 4 weeks prior to study start

Exclusion Criteria:

  • Transfusion of red blood cells during previous 8 weeks
  • Poorly controlled hypertension requiring interruption of ESA treatment in previous 6 months
  • Significant acute or chronic bleeding during previous 8 weeks
  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: NCT00737477

Locations
France
Ajaccio, France, 20303
Annonay, France, 07103
Auxerre, France, 89011
Beuvry, France, 62660
Bordeaux, France, 33300
Cabestany, France, 66330
Caen, France, 14033
Chalon-sur-Saone, France, 71100
Chambery, France, 73001
Charleville-Mezieres, France, 08011
Chartres, France, 28000
Colmar, France, 68024
Creil, France, 60100
Dunkerque, France, 59385
Evreux, France, 27023
La Tronche, France, 38701
Lyon, France, 69437
Niort, France, 79021
Orleans, France, 45100
Paris, France, 75013
Paris, France, 75877
Poitiers, France, 86021
Pontoise, France, 95300
Reims, France, 51092
Saint-Denis, France, 97400
Saint-Lo, France, 50009
Saint-Priest-en-Jarez, France, 42277
Soissons, France, 02209
Strasbourg, France, 67091
Valence, France, 26953
Vandoeuvre-les-Nancy, France, 54511
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00737477     History of Changes
Other Study ID Numbers: ML21421  2008-001747-18 
Study First Received: August 18, 2008
Results First Received: June 17, 2016
Last Updated: June 17, 2016
Health Authority: France: Agence Francaise de Securite Sanitaire des Produits de Sante (AFSSAPS)

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Epoetin Alfa
Hematinics

ClinicalTrials.gov processed this record on August 24, 2016