Advertisement

Topics

Epoetin Dosing Regimens in Haemodialysis

2014-08-27 03:43:36 | BioPortfolio

Summary

Currently, less frequent than once weekly subcutaneous epoetin administration regimens were shown to be equally effective and safe as the once-weekly schedules in stable pre-dialyzed and peritoneal dialyzed patients Bioequivalence of once-every-two-weeks and once-weekly subcutaneous administration of the same total dose of epoetin beta for the maintenance phase of anemia treatment in stable, iron-replete, chronic hemodialyzed patients was therefore prospectively investigated.

two treatment schedules will be considered equivalent if the primary efficacy parameters will be simultaneously similar for both groups and in the predefined range of variation. Confidence intervals (CIs) will be used to compare groups. Since the target Hb in dialyzed patients is defined as 11g/dL (110 g/L) by the European Guidelines and as >10 g/dL (100 g/L) by the National Guidelines, with a recommended upper limit of 13 g/dL (130 g/L), the efficacy range for Hb in this study was predefined as 10-12 g/dL (100-120 g/L). The two treatment schedules will be considered to have similar efficacy if the mean Hb in Group 2w will not differ by more than ±0.5 g/dL (±5 g/L) compared to Group 1w during the assessment period. Once similar efficacy established, drug requirements will be compared calculating the ratio of the mean weekly epoetin doses in Group 2w/Group 1w. A range of 0.8 to 1.25 for the ratio is considered sufficient to define bioequivalence. Equivalence of drug usage in the two arms will be accepted if the whole 95% CI for this ratio will be within the above limits.

Lack of difference between group means does not imply similar distribution of treatment effects within each group. The individual hemoglobin change will be used to assess if response to treatment was similarly variable in the two arms. The change in Hb will be calculated for each patient as the difference between the mean Hb during the assessment period and the mean Hb during the baseline phase.

Description

Current European Best Practice Guidelines and the KDOQI Committee in the USA recommend preferential subcutaneous (SC) twice- to thrice-weekly epoetin administration. SC route significantly reduces epoetin requirements and therefore costs, compared to the intravenous (IV) route. Additionally, there is solid evidence showed once-weekly SC administration of epoetin beta to be equally efficient and well tolerated in hemodialyzed (HD) patients. Clinical studies suggest that the effects of epoetin alpha are sustained for more than one week, enabling less frequent schedules in pre-dialysis chronic kidney disease (CKD) patients. A recent European multicenter study in peritoneal dialysis (PD) patients confirmed that once-every-two-weeks SC epoetin beta is efficient and safe in the maintenance phase of anemia treatment for PD patients11. Thus, the optimum epoetin dosing regimen is still yet to be determined despite over a decade of clinical use.

All these data also suggest that the pharmacodynamic effects of epoetins could last longer than their plasma half-lives. The survival half-life of erythrocytes produced after exogenous epoetin administration is longer than that of erythrocytes produced in the absence of exogenous stimulation.

Apart of the academic interest, this issue has also direct implications on cost savings and increased patients’ convenience. Furthermore, less frequent administration would reduce epidemiological hazards associated with populations at high risk of blood-borne viral infections such as hepatitis, particularly important in less developed countries, with a high prevalence of viral hepatitis infections (hepatitis B/C markers prevalences: 15.7%/45% in Romania versus 3%/13.5% in EuroDOPPS patients). While the potential benefits of less frequent dosing are clear, the efficacy and safety of such regimens must be fully investigated before adoption as standard treatment.

The present study investigates for the first time the equivalence of once-weekly versus once-every-two-weeks SC epoetin beta dosing regimens, in the maintenance phase of anemia therapy, in stable HD patients. The aim of the study is to assess whether once-every-other-week SC administration of the same total epoetin beta dose is as effective and as safe as SC once-weekly dosing.

In order to avoid a carry-over effect of the weekly schedule of epoetin treatment received prior to randomization, we defined a run-in period (weeks 1-12). Statistical analyses will be performed for the efficacy parameters determined during the assessment period only. The average for weeks 13-24 will be obtained by adding all values and dividing the sum by the number of time points for each patient during this period.

The two treatment schedules will be considered equivalent if the primary efficacy parameters will be simultaneously similar for both groups and in the predefined range of variation. Confidence intervals (CIs) will be used to compare groups. Since the target Hb in dialyzed patients is defined as 11g/dL (110 g/L) by the European Guidelines and as >10 g/dL (100 g/L) by the National Guidelines, with a recommended upper limit of 13 g/dL (130 g/L), the efficacy range for Hb in this study was predefined as 10-12 g/dL (100-120 g/L). The two treatment schedules will be considered to have similar efficacy if the mean Hb in Group 2w will not differ by more than ±0.5 g/dL (±5 g/L) compared to Group 1w during the assessment period. Once similar efficacy established, drug requirements will be compared calculating the ratio of the mean weekly epoetin doses in Group 2w/Group 1w. A range of 0.8 to 1.25 for the ratio is considered sufficient to define bioequivalence. Equivalence of drug usage in the two arms will be accepted if the whole 95% CI for this ratio will be within the above limits.

Lack of difference between group means does not imply similar distribution of treatment effects within each group. The individual hemoglobin change will be used to assess if response to treatment was similarly variable in the two arms. The change in Hb will be calculated for each patient as the difference between the mean Hb during the assessment period and the mean Hb during the baseline phase. The percentages of patients with target Hb and not requiring any increase in epoetin dose during the assessment period will be compared with chi-squared statistic.

The study is designed to detect a difference in Hb between the study groups of at least 0.5 g/dL (5 g/L), with a probability of 95% and a power of 0.9021, assuming a standard deviation of Hb in the HD population of 1.0 g/dL (10 g/L). A sample size of 85 patients is required in each arm of the trial. Since the study design includes epoetin doses variations in order to maintain target hemoglobin, it would have been expected that Hb would be constant and epoetin dose would vary. Therefore, the power calculations using epoetin doses as the outcome measure seem to be more appropriate. Considering a standard deviation of 39 IU/kg per week, a probability of 95% and a power of 90%, a sample size of 70 patients in each arm is required to detect a ± 20% difference in epoetin dose between groups. Because of an anticipated drop-out proportion of 15%, a minimum of 100 patients have to be enrolled in each group to satisfy both Hb and epoetin doses power conditions.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Hemodialyzed Patients

Intervention

NeoRecormon SC once-weekly versus once-every-other-week

Location

"Dr Carol Davila" Teaching Hospital of Nephrology
Bucharest
Romania
010731

Status

Completed

Source

Romanian Society of Nephrology

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:43:36-0400

Clinical Trials [747 Associated Clinical Trials listed on BioPortfolio]

A Study of NeoRecormon (Epoetin Beta) in Patients With Renal Anemia.

This study will determine whether 8 weekly monitoring of hemoglobin and iron parameters in the correction phase of NeoRecormon therapy in patients with renal anemia is as safe and effectiv...

A Study of the Quality of Life and Treatment Response to Once Weekly NeoRecormon (Epoetin Beta) Treatment in Anemic Patients With Solid and Lymphoid Malignancies.

This 2 arm study will investigate Quality of Life response in anemic patients wi th solid and lymphoid malignancies, who are receiving concomitant chemotherapy. Patients in treatment Arm 1...

A Study of NeoRecormon in Patients With Chronic Kidney Disease.

This 2 arm study will compare the level of anemia, and the decline in renal function, between patients receiving NeoRecormon, and those not receiving it. Patients with chronic kidney disea...

A Study of NeoRecormon (Epoetin Beta) in Patients With End Stage Renal Disease.

This single arm study will determine the effects of complete anemia correction in anemic patients with end-stage renal disease currently receiving suboptimal doses of NeoRecormon. Patients...

A Study of Treatment With NeoRecormon (Epoetin Beta) in Patients With Chronic Renal Anemia

This study will evaluate whether anemia prevention with NeoRecormon has an additional impact on reducing cardiovascular risk over conventional anemia treatment in patients mostly with stag...

PubMed Articles [6090 Associated PubMed Articles listed on BioPortfolio]

Safety and Convenience of Once-Weekly Somapacitan in Adult GH Deficiency: A 26-Week Randomized, Controlled Trial.

Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily N...

Ensemble method for dengue prediction.

In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico) during four dengue seasons: 1) peak height (i.e., maxi...

The organised chaos of English adolescent rugby union: Influence of weekly match frequency on the variability of match and training loads.

The aims of this study were to determine the variability of weekly match and training loads in adolescent rugby union players across a competitive season, and to investigate the effect of match freque...

Role of Bi-Weekly Serum Galactomannan Screening for the Diagnosis of Invasive Aspergillosis in Hematologic Cancer Patients.

Invasive aspergillosis (IA) is a life-threatening infection affecting hematologic cancer patients with chemotherapy-induced neutropenia. The diagnosis of IA often relies on the detection of galactoman...

Effects of anxiety on suicidal ideation: exploratory analysis of a paroxetine versus bupropion randomized trial.

It is unclear whether anxiety increases or decreases suicidal risk. This may contribute to the lack of guidance on which antidepressant medications are best for suicidal depressed patients who present...

Medical and Biotech [MESH] Definitions

Blood infection that occurs in an infant younger than 90 days old. Early-onset sepsis is seen in the first week of life and most often appears within 24 hours of birth. Late-onset occurs after 1 week and before 3 months of age.

Publications printed and distributed daily, weekly, or at some other regular and usually short interval, containing news, articles of opinion (as editorials and letters), features, advertising, and announcements of current interest. (Webster's 3d ed)

Publications printed and distributed daily, weekly, or at some other regular and usually short interval, containing news, articles of opinion (as editorials and letters), features, advertising, and announcements of current interest. (Webster's 3d ed)

Personality construct referring to an individual's perception of the locus of events as determined internally by his or her own behavior versus fate, luck, or external forces. (ERIC Thesaurus, 1996).

Deaths occurring from the 28th week of GESTATION to the 7th day after birth.

More From BioPortfolio on "Epoetin Dosing Regimens in Haemodialysis"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Pharmacy
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...


Searches Linking to this Trial