Bio-Equivalency of 2 Treatment Schedules in HD PatientsPhase 4VAESNCT00551603
Anaemia Correction in Haemodialyzed Patients - Comparative Analysis of Two Erythropoietin Stimulating Agents Schedules
A Phase 4 study testing switch (epoetinum beta, darbepoetinum) and continuation (darbepoetinum) in people with Bio-Equivalency of 2 Treatment Schedules in HD Patients, run by Anemia Working Group Romania at 2 sites in Romania.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bio-Equivalency of 2 Treatment Schedules in HD Patients
- What is being tested?
- switch (epoetinum beta, darbepoetinum) and continuation (darbepoetinum)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesRomania
- Study dates
- Jul 2006to Mar 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%.
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Romania2 sites
"Dr Carol Davila" Fresenius NephroCare Dialysis Centre
Bucharest, 0107231
IHS Dialysis Centre "Sf Ioan Nou" Clinical Hospital
Bucharest
About this study
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.
Read more
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
Read the 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.
- Being tested
- switch (epoetinum beta, darbepoetinum), continuation (darbepoetinum)
- Keywords
- epoetinum beta once-weekly, darbepoetinum once-fortnightly, anemia correction, hemoglobin stability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
switch (epoetinum beta, darbepoetinum)Drug
Also called Group Epo
switching from epoetinum beta once weekly to once-fortnightly darbepoetinum
continuation (darbepoetinum)Drug
Also called Darbepo Group
continuation of the previous darbepoetinum administration schedule
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Group Epo will receive anaemia treatment according to the Romanian Best Practice Guidelines recommendation, with once-weekly SC epoetinum beta during the first phase, then will be switched to receive SC once-fortnightly darbepoetinum. Anaemia treatment schedule will continue according to the Romanian Best Practice Guidelines recommendations, with the same dose. A conversion factor of 1:200 will be used. Receives: Drug: switch (epoetinum beta, darbepoetinum) |
| 2 | Active comparator | Subjects in the Darbepo Group will receive anaemia treatment according to the Romanian Best Practice Guidelines recommendation, with once-fortnightly or once-monthly darbepoetin SC administration, continuing their previous schedule and will continue their previous schedule of anaemia treatment during the second phase of the study Receives: Drug: continuation (darbepoetinum) |
What is being measured
The primary outcome is the main question the study is designed to answer.
- hemoglobin level during the study and - monthly ESA dose per dry body weight during the study
Measured: 80 weeks of the study
Secondary outcomes (1)
- 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
Measured: during the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2007 (estimated)
- Study startJul 2006
- Primary completionDec 2008
- Study completionMar 2009
Why it stopped: Logistic reasons, financial contrastraints
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bio-Equivalency of 2 Treatment Schedules in HD PatientsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anemia Working Group Romania
- Sponsor type
- University, hospital or other
- Collaborators
- Dr Carol Davila Teaching Hospital of Nephrology, Romanian Renal Registry
- Responsible party
- Sponsor
- Investigators
- Liliana Garneata, MD, PhD, Study director, Anemia Working GroupGabriel Mircescu, Professor, Study chair, Anemia Working GroupCarmen Barbulescu, MD, Principal investigator, "Dr Carol Davila" NephroCare Dialysis CentreAlexandru Ciocalteu, Professor, Study director, "IHS" Dialysis Centre "Sf Ioan Nou" Clinical HospitalDaniela Ciortea, MD, PhD, Principal investigator, IHS Dialysis Centre, "Sf Ioan Nou" Clinical Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00551603
- Sponsor's protocol ID
- AWG_03_07
- Other IDs
- 1246/ANM
- Acronym
- VAES
- Status last verified
- Dec 2017
- First submitted
- 29 Oct 2007
- Last updated
- 22 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Rath T, Mactier RA, Weinreich T, Scherhag AW; GAIN Investigators. Effectiveness and safety of recombinant human erythropoietin beta in maintaining common haemoglobin targets in routine clinical practice in Europe: the GAIN study. Curr Med Res Opin. 2009 Apr;25(4):961-70. doi: 10.1185/03007990902784459.
PubMed 19254204
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anaemia Correction in Haemodialyzed Patients - Comparative Analysis of Two Erythropoietin Stimulating Agents Schedules
- ClinicalTrials.gov ID
- NCT00551603
- Acronym / sponsor ID
- VAES / AWG_03_07
- Keywords
- epoetinum beta once-weekly, darbepoetinum once-fortnightly, anemia correction, hemoglobin stability
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Logistic reasons, financial contrastraints
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Anemia Working Group RomaniaUniversity, hospital or other
- Collaborators
- Dr Carol Davila Teaching Hospital of Nephrology, Romanian Renal Registry
- Study start
- Jul 2006 (actual)
- Primary completion
- Dec 2008 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 31 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: switch (epoetinum beta, darbepoetinum)Group Epo will receive anaemia treatment according to the Romanian Best Practice Guidelines recommendation, with once-weekly SC epoetinum beta during the first phase, then will be switched to receive SC once-fortnightly darbepoetinum. Anaemia treatment schedule will continue according to the Romanian Best Practice Guidelines recommendations, with the same dose. A conversion factor of 1:200 will be used. |
| 2 | Active comparator | Drug: continuation (darbepoetinum)Subjects in the Darbepo Group will receive anaemia treatment according to the Romanian Best Practice Guidelines recommendation, with once-fortnightly or once-monthly darbepoetin SC administration, continuing their previous schedule and will continue their previous schedule of anaemia treatment during the second phase of the study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| switch (epoetinum beta, darbepoetinum)Also: Group Eposwitching from epoetinum beta once weekly to once-fortnightly darbepoetinum | Drug | 1 |
| continuation (darbepoetinum)Also: Darbepo Groupcontinuation of the previous darbepoetinum administration schedule | Drug | 2 |
Primary outcome
- hemoglobin level during the study and - monthly ESA dose per dry body weight during the study
Time frame: 80 weeks of the study
1 secondary outcome
- 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
Time frame: during the study
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2017.
- Derived from this study: PubMed 19254204Rath T, Mactier RA, Weinreich T, Scherhag AW; GAIN Investigators. Effectiveness and safety of recombinant human erythropoietin beta in maintaining common haemoglobin targets in routine clinical practice in Europe: the GAIN study. Curr Med Res Opin. 2009 Apr;25(4):961-70. doi: 10.1185/03007990902784459.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Liliana Garneata, MD, PhD study director
Anemia Working Group
Gabriel Mircescu, Professor study chair
Anemia Working Group
Carmen Barbulescu, MD principal investigator
"Dr Carol Davila" NephroCare Dialysis Centre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing switch (epoetinum beta, darbepoetinum) and continuation (darbepoetinum) in people with Bio-Equivalency of 2 Treatment Schedules in HD Patients, run by Anemia Working Group Romania at 2 sites in Romania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
- hemoglobin level during the study and - monthly ESA dose per dry body weight during the study (time frame: 80 weeks of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00551603, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2017.