A Study of Mircera for the Maintenance Treatment of Anemia in Dialysis Patients

• ClinicalTrials.gov Identifier: NCT00394953
• Recruitment Status: Completed
• First Posted: November 2, 2006
• Results First Posted: January 20, 2017
• Last Update Posted: January 20, 2017
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This 2 arm study will compare the efficacy and safety of Mircera and darbepoetin alfa, administered at extended dosing intervals, in the maintenance treatment of anemia in patients with chronic kidney disease (CKD) who are on hemodialysis. Eligible patients receiving once-weekly intravenous (IV) darbepoetin alfa maintenance treatment will be randomized to receive either intravenous Mircera once a month (at a starting dose of 120, 200 or 360 micrograms/month, depending on the weekly dose of darbepoetin alfa prior to start of study) or intravenous darbepoetin alfa every 2 weeks before switching to once monthly administration. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Condition or disease	Intervention/treatment	Phase
Anemia	Drug: Darbepoetin alfa; Drug: methoxy polyethylene glycol-epoetin beta [Mircera]	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 490 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Controlled, Open Label, Multicenter, Parallel-group Study to Compare the Effect of Mircera With That of Darbepoetin Alfa, Administered Intravenously at Extended Dosing Intervals, for the Maintenance Treatment of Anemia in Patients With Chronic Kidney Disease Who Are on Hemodialysis
• Study Start Date: December 2006
• Actual Primary Completion Date: November 2008
• Actual Study Completion Date: November 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: MIRCERA; Eligible participants with anemia in CKD who were on hemodialysis will receive methoxy polyethylene glycol-epoetin beta (MIRCERA [RO0503821]) IV once every month up to 52 weeks. The starting dose of MIRCERA which will be administered during the treatment period will depend on the dose of darbepoetin alfa administered during screening period i.e., 120, 200 and 360 mcg for weekly darbepoetin alfa doses of <40, 40-80, and >80 mcg, respectively.	Drug: methoxy polyethylene glycol-epoetin beta [Mircera]; 120, 200 or 360 micrograms iv / month, starting dose
Active Comparator: Darbepoetin Alfa; Eligible participants with anemia in CKD who were on hemodialysis will receive darbepoetin alfa (Aranesp) IV once every two weeks up to 26 weeks and darbepoetin alfa IV twice the dose than earlier, once every month from Week 27 up to Week 52.	Drug: Darbepoetin alfa; As prescribed, iv.; Other Name: Aranesp

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Lesser Than or Equal to One Gram Per Deciliter Decrease in Average Hemoglobin From Baseline and Maintaining Average Hemoglobin Level Greater Than or Equal to 10.5 g/dL Over Evaluation Period [ Time Frame: Baseline (Week -4 to Week -1) and Evaluation period (Weeks 50 to 53) ]
   Randomized participants with an average hemoglobin (Hb) decrease from Baseline (Week -4 to Week -1) not exceeding 1.0 gram per deciliter (g/dL) and an absolute average Hb >= 10.5 g/dL during the evaluation period (Weeks 50-53) were defined as responders. Non-responders included participants without any Hb data during the second treatment period and those who did not meet the response criteria and thus were not included in the analysis.

Secondary Outcome Measures :

1. Mean Percentage Change in MIRCERA and Darbepoetin Alpha Dose Over Time [ Time Frame: Week 27 to Month 12 ]
   All participants received once monthly treatment schedule of both MIRCERA and darbepoetin alpha for the respective treatment arms after Week 27 and these analyses are based on the absolute doses. The average dose in Months 11 and 12 was defined as the mean of all administered doses between study Days 302 and 363. The change in dose was calculated as the percentage change between the respective dose at Week 27 and the average corresponding dose during Months 11 and 12 in each treatment group.
2. Number of Participants With Marked Laboratory Abnormality Over Time [ Time Frame: Up to Week 53 ]
   Values of laboratory parameters higher (H) or lower (L) than the Roche defined reference range were considered as abnormality. The laboratory parameters with abnormality were platelets, white blood cells (WBC), albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and potassium. Blood samples were drawn before drug administration and before the dialysis session.
3. Median Blood Pressure Over Time [ Time Frame: Baseline (Week -4 to Week -1), Week 28, and Week 52 ]
   Systolic and diastolic blood pressures (BP) were measured before and after the dialysis session at every week from Baseline (Week -4 to Week -1) to Week 53. Median pre-dialysis diastolic blood pressure (PrD DBP) , median post-dialysis diastolic blood pressure (PoD DBP), median pre-dialysis systolic blood pressure (PrD SBP), and post-dialysis systolic blood pressure (PoD SBP) were reported at Baseline (Week -4 to Week -1) , Week 28 and Week 52.
4. Mean Pulse Rate Over Time [ Time Frame: Baseline (Week -4 to Week -1), Week 28, and Week 52 ]
   Pulse rate is defined as the number of heartbeats in a minute and was assessed in sitting position of the participants at every week from Baseline (Week -4 to Week -1) to Week 53. Summary data of mean values of pulse rate are presented at Baseline (Week -4 to Week -1), Week 28 and Week 52.
5. Number of Participants With Any Adverse Events, Serious Adverse Events, and Deaths [ Time Frame: From screening to Week 56 ]
   An adverse event (AE) can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. A serious adverse event (SAE) is any adverse event that can result in death or is life-threatening or required in participants hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect; or is medically significant or requires intervention to prevent one or other of the outcomes listed above. SAEs were reported up to Week 56, while nonserious AEs up to Week 52.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• adult patients, >=18 years of age;
• chronic renal anemia;
• hemodialysis 3 times weekly for >=12 weeks before screening, and during screening/baseline period;
• receiving darbepoetin alfa maintenance therapy for >=8 weeks before screening, and during screening/baseline period.

Exclusion Criteria:

• overt gastrointestinal bleeding within 8 weeks before screening or during screening/baseline period;
• transfusion of red blood cells within 8 weeks before screening or during screening/baseline period;
• active malignancy;

Contacts and Locations

  Hide Study Locations

Locations

Australia

Adelaide, Australia, SA 5000

Clayton, Australia, 3186

Gosford, Australia, 2250

Parkville, Australia, 3052

Woolloongabba, Australia, 4102

Austria

Linz, Austria, 4010

Wien, Austria, 1090

Wien, Austria, 1220

Belgium

Aalst, Belgium, 9300

Bruxelles, Belgium, 1020

Bruxelles, Belgium, 1200

Roeselare, Belgium, 8800

Canada, Alberta

Calgary, Alberta, Canada, T2N 2T9

Canada, Ontario

Hamilton, Ontario, Canada, L8N 4A6

Kitchener, Ontario, Canada, N2G 1N9

Mississauga, Ontario, Canada, L5M 2V8

Ottawa, Ontario, Canada, K1H 7W9

Toronto, Ontario, Canada, M5G 2C4

Canada, Quebec

Greenfield Park, Quebec, Canada, J4V 2H1

Trois-rivieres, Quebec, Canada, G8Z 4K8

Denmark

Aalborg, Denmark, 9100

Hillerød, Denmark, 3400

Roskilde, Denmark, 4000

Finland

Tampere, Finland, 33521

Turku, Finland, 20521

France

Auch, France, 32000

Bordeaux, France, 33000

Boulogne, France, 62321

Castelnau Le Lez, France, 34170

Cergy Pontoise, France, 95303

Chamalieres, France, 63400

Dijon, France, 21079

Fleury-merogis, France, 91712

Herouville Saint Clair, France, 14202

La Tronche, France, 38701

Lyon, France, 69437

Montpellier, France, 34295

Nimes, France, 30029

Paris, France, 75015

Paris, France, 75970

Reims, France, 51092

Rennes, France, 35033

Saint Herblain, France, 44093

Saint Ouen, France, 93400

St Brieuc, France, 22027

Villeurbanne, France, 69100

Germany

Bad Hersfeld, Germany, 36251

Bonn, Germany, 53127

Dortmund, Germany, 44263

München, Germany, 80804

Stuttgart, Germany, 70191

Villingen-schwenningen, Germany, 78054

Italy

Bologna, Italy, 40138

Como, Italy, 22100

Genova, Italy, 16132

Lecco, Italy, 23900

Modena, Italy, 41100

Pavia, Italy, 27100

Prato, Italy, 50047

Venezia, Italy, 30122

Netherlands

Amsterdam, Netherlands, 1081 HV

Dordrecht, Netherlands, 3318 AT

Portugal

Leiria, Portugal, 2400-441

Spain

Alicante, Spain, 03010

Badalona, Spain, 08915

Barcelona, Spain, 08003

Barcelona, Spain, 08036

Bilbao, Spain, 48013

Córdoba, Spain, 14004

Leon, Spain, 24071

Madrid, Spain, 28003

Madrid, Spain, 28035

Madrid, Spain, 28040

Madrid, Spain, 28041

Madrid, Spain, 28046

Madrid, Spain, 28222

Orense, Spain, 32005

Santander, Spain, 39008

Vigo, Spain, 36204

Vigo, Spain, 36205

Switzerland

Aarau, Switzerland, 5001

Lausanne, Switzerland, 1003

United Kingdom

Belfast, United Kingdom, BT9 7LJ

Canterbury, United Kingdom, CT1 3NE

Glasgow, United Kingdom, G4 OSF

London, United Kingdom, SE22 8PT

Manchester, United Kingdom, M13 9WL

Truro, United Kingdom, TR1 3LJ

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Carrera F, Lok CE, de Francisco A, Locatelli F, Mann JF, Canaud B, Kerr PG, Macdougall IC, Besarab A, Villa G, Kazes I, Van Vlem B, Jolly S, Beyer U, Dougherty FC; PATRONUS Investigators. Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial. Nephrol Dial Transplant. 2010 Dec;25(12):4009-17. doi: 10.1093/ndt/gfq305. Epub 2010 Jun 3.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00394953 History of Changes
• Other Study ID Numbers: BH17847
• First Posted: November 2, 2006
• Results First Posted: January 20, 2017
• Last Update Posted: January 20, 2017
• Last Verified: November 2016

Additional relevant MeSH terms:

Anemia; Hematologic Diseases; Epoetin Alfa; Darbepoetin alfa; Hematinics