Bio-Equivalency of 2 Treatment Schedules in HD Patients
Conditions
Keywords
epoetinum beta once-weekly, darbepoetinum once-fortnightly, anemia correction, hemoglobin stability
Brief summary
Several recent reports support the efficacy of once every-other-week epoetinum administration in the maintenance phase of the anaemia treatment in predialysis, haemodialysis and in peritoneal dialysis CKD patients. However, there are studies suggesting that in HD patients receiving SC short-acting ESA therapy, ESA efficacy decreases when the dosing is extended from thrice-weekly to once-weekly administration. When every-2-week administration of long-acting ESAs is extended to every 4 weeks, efficacy either remains stable or decreases incrementally. The GAIN trial (Gain effectiveness in Anemia treatment with NeoRecormon®) was designed to compare anemia management with epoetin beta, epoetin alpha or darbepoetin alpha in HD patients. An interim analysis of data from 1005 stable HD patients suggested that switching to epoetin beta from either epoetin alpha or darbepoetin alpha resulted in improved efficacy and a 20% dose reduction in SC epoetin beta. The aim of the study is to compare two schedules of anaemia treatment in HD patients using two different erythropoietic stimulating agents (epoetinum beta vs darbepoetinum) with respect to the efficacy in anaemia correction and to the haemoglobin (Hb) level stability. This is a multicenter (2 centers), prospective, open-label, parallel, controlled trial of therapy equivalence
Detailed description
Currently available ESAs include epoetin alfa, epoetin beta, and darbepoetin. Epoetin alfa and beta have been designed to resemble closely the endogenous molecule and have similar pharmacokinetics. They are considered short-acting in comparison to darbepoetin, a second-generation molecule with a prolonged half-life, which is considered long-acting. European and American Best Practice Guidelines (EBPG) recommend preferential subcutaneous (SC) twice- to thrice-weekly epoetin administration. There is a great deal of evidence that once-weekly SC administration of epoetin beta to be equally efficient and well tolerated in HD patients, even in those requiring high weekly epoetin doses. Several recent reports support the efficacy of once every-other-week epoetinum administration in the maintenance phase of the anaemia treatment in predialysis, haemodialysis and in peritoneal dialysis CKD patients. However, there are studies suggesting that in HD patients receiving SC short-acting ESA therapy, ESA efficacy decreases when the dosing is extended from thrice-weekly to once-weekly administration. When every-2-week administration of long-acting ESAs is extended to every 4 weeks, efficacy either remains stable or decreases incrementally . The GAIN trial (Gain effectiveness in Anemia treatment with NeoRecormon®) was designed to compare anemia management with epoetin beta, epoetin alpha or darbepoetin alpha in HD patients. An interim analysis of data from 1005 stable HD patients suggested that switching to epoetin beta from either epoetin alpha or darbepoetin alpha resulted in improved efficacy and a 20% dose reduction in SC epoetin beta. The aim of the study is to compare two schedules of anaemia treatment in HD patients using two different erythropoietic stimulating agents (epoetinum beta vs darbepoetinum) with respect to the efficacy in anaemia correction and to the haemoglobin (Hb) level stability. The trial is designed according to the Guidelines for studies testing the equivalence of different treatment regimens , and will be conducted with the provisions of the Declaration of Helsinki and Tokio as amended in Venice (1983). This is a multicenter (2 centers), prospective, open-label, parallel, controlled trial of therapy equivalence. The total observation period is of 80 weeks: * The baseline phase (pre-therapeutic intervention) - 12 weeks; * The first study phase of therapeutical intervention - 48 weeks: each the two groups of patients will receive anaemia treatment according to the Romanian Best Practice Guidelines either with epoetinum beta or with darbepoetinum; * The second study phase of therapeutical intervention - 24 weeks: the patients from the epoetinum beta group will be switched to darbepoetinum. The anaemia treatment will continue according to the Romanian Best Practice Guidelines, using the recommended conversion factor of 200 (Romanian Best Practice Guidelines, NKF-DOQI 2006, Revised EBPG). 300 haemodialyzed patients will be enrolled.
Interventions
DRUGswitch (epoetinum beta, darbepoetinum)
switching from epoetinum beta once weekly to once-fortnightly darbepoetinum
DRUGcontinuation (darbepoetinum)
continuation of the previous darbepoetinum administration schedule
Sponsors
Dr Carol Davila Teaching Hospital of Nephrology
Romanian Renal Registry
Anemia Working Group Romania
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult age (≥18 years) * at least 6 months HD * efficient HD (urea-equilibrated Kt/V \>1.2, Daugirdas II equation) * haemoglobin (Hb) levels above 10g/dL * treatment with an ESA for at least 12 weeks prior to enrollment * serum ferritin level 100-800 ng/mL * transferrin saturation 20-50%.
Exclusion criteria
* hepatic diseases (as defined by abnormal ALT and AST levels) or association of psychical disorders or other disturbances making the enrollment unacceptable, as judged by the physician * acute infection or HIV infection * severe hyperparathyroidism (iPTH \>800 ng/mL) * active bleeding * \> 5% variation in dry body weight in the last 6 months * previously diagnosed folic acid and/or vitamin B12 deficiency * neoplastic diseases * other known causes of anaemia * known hypersensibility to one of the administered drugs * epilepsy * pregnancy or lactation * anti-viral treatment during the month before the inclusion * immunosuppressive treatment or use of other medication known to influence erythropoiesis during the month preceding the enrollment * need for blood transfusions within 12 weeks prior to enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - hemoglobin level during the study and - monthly ESA dose per dry body weight during the study | 80 weeks of the study |
Secondary
| Measure | Time frame |
|---|---|
| - percentage of patients maintaining target Hb without increase in ESA dose - difference between the average Hb during second study phase period versus the first one and versus baseline phase | during the study |
Countries
Romania
Outcome results
None listed