HemochromatosisNCT00509652
Erythrocyte Apheresis Versus Phlebotomy in Hemochromatosis
A study testing Arm 1: Erythrocyte apheresis and Arm 2: Whole blood phlebotomy in people with Hemochromatosis, run by University of Bergen at 3 sites in Norway.
Trial summary
Primary hemochromatosis is the most frequent hereditary condition in Scandinavia. The condition may result in serious organ damage which can be prevented by therapy, but only few patients develop such organ damage. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hemochromatosis
- What is being tested?
- Arm 1: Erythrocyte apheresis and Arm 2: Whole blood phlebotomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 3 sitesNorway
- Study dates
- Jan 2006to Dec 2009
- Phase
- Interventional
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis
- Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%.
- Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%.
- Requirements to the patient Body weight higher than 65 kg and initial hemoglobin level higher than 12 g/dL.
Who cannot join
- Contra-indications to either treatment modality
- Patients who are not able to co-operate
- Lack of informed consent
Trial locations and contacts
3 sites in 1 country.
Norway3 sites, 3 recruiting
- Recruiting
Haukeland University Hospital, Department of Transfusion Medicine
Bergen, N-5021
Tor Hervig, MD, PhD, +47-55975000, tor.hervig@helse-bergen.no
Signe Hannisdahl, +47-55975000, signe@hannisdahl@helse-bergen.no
- Recruiting
Haugesund Hospital, Department of Immunology and Transfusion Medicine
Haugesund, N-5504
Tatjana Sundic, MD, +47-52732000, tatjana.sundic@helse-fonna.no
Sigbjorn Berentsen, MD, PhD, +47-52732000, s.beren@online.no
- Recruiting
Akershus University Hospital (AHUS), Department of Transfusion Medicine
Nordbyhagen, N-1474
Richard W Olaussen, MD, +47-67928800, richard.olaussen@ahus.no
About this study
Official title: Therapeutic Effect of Erythrocyte Apheresis as Compared to Full Blood Phlebotomy in Patients With Hereditary Hemochromatosis
Primary hemochromatosis is the most frequent hereditary condition in Scandinavia. The condition may result in serious organ damage which can be prevented by therapy, but only few patients develop such organ damage. The optimal treatment, therefore, is still a matter of discussion Prevention of organ damage has traditionally been accomplished by drawing of full blood (phlebotomy), which has to be frequently repeated during the initial phase and then continued indefinitely as a maintenance treatment. The removed amount of iron may be increased two- or threefold for each procedure by using modern equipment for selective removal of red blood cells (red cell apheresis). Possible drawbacks of this technique may be higher costs, prolonged time for each therapeutic procedure, and certain requirements to the patients. The possible advantages are the reduced number of therapeutic procedures and less strain for the patient. No larger, randomized study has been published in order to determine which method should be preferred.
This study is a controlled trial in which participating patients are asked to be randomized to red cell apheresis or traditional phlebotomy. Each group will be followed by means of well-defined assessments in order to explore possible advantages and disadvantages of each method in order to establish what type of treatment should be recommended.
Read the detailed description
Introduction Primary hemochromatosis is the most frequent hereditary condition in Scandinavia. The condition may result in serious organ damage which can be prevented by therapy, but only few patients develop such organ damage. Provided the lack of more exact knowledge of which patients should be treated, we have based our inclusion criteria on the guidelines published by the Norwegian Society of Hematology. However, the criteria for ferritin levels have been set at 300 micrograms/L for patients who are homozygous for the C282Y mutation, and also heterozygous individuals will be included if ferritin is higher than 500 micrograms/L.
Furthermore, the optimal treatment method is still a matter of discussion. Prevention of organ damage has traditionally been accomplished by whole blood phlebotomy, which has to be frequently repeated during the initial phase and then continued indefinitely as a maintenance treatment. The removed amount of iron may be increased two- or threefold for each procedure by using modern equipment for selective withdrawal of red blood cells (erythrocyte apheresis). Possible drawbacks of this technique may be higher costs, prolonged time for each therapeutic procedure, and certain requirements to the patients. The possible advantages are the reduced number of therapeutic procedures and less strain for the patient. No larger, randomized study has been published in order to determine which method should be preferred.
Hypothesis: A more rapid decline of primary endpoints (see below) can be achieved by erythrocyte apheresis as compared to traditional phlebotomy, without significant disadvantages.
Design The trial is prospective, randomized and open. Eligible patients are randomized to erythrocyte apheresis and phlebotomy.
Endpoints Primary endpoints Decline of ferritin levels and transferrin saturation.
Secondary endpoints and other variables to be studied Decline in hemoglobin levels. Discomfort during the therapeutic procedure. Any changes in EVF, blood cell counts or albumin and CRP levels. Certain well-defined financial costs: consumed material, technician working time.
Inclusion criteria
- Diagnosis
- Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%.
- Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%.
- Requirements to the patient Body weight higher than 65 kg and initial hemoglobin level higher than 12 g/dL.
Treatment schedule Following randomization to either apheresis or phlebotomy, patients are treated until ferritin levels have declined to below 50 micrograms/L and they are then followed for one year. Patients randomized to apheresis are treated every second week, whereas patients in the phlebotomy group are treated weekly. Prolongation of the interval is permitted in both groups in case of well-defined clinical indications. Any prolongation is to be recorded along with the clinical indication.
Follow-up Clinical symptoms, body weight, laboratory findings (Hemoglobin levels; blood cell counts; levels of iron, transferrin, ferritin, albumin and IgG; serologic assessments for hepatitis viruses, CMV and HIV), discomfort during the therapeutic procedure, duration of each procedure, costs for consumed material, working time of the technician for each procedure.
- Conditions
- Hemochromatosis
- Being tested
- Arm 1: Erythrocyte apheresis, Arm 2: Whole blood phlebotomy
- Keywords
- Hemochromatosis, Primary hemochromatosis, Hereditary hemochromatosis, Therapy, Erythrocyte apheresis, Phlebotomy, Apheresis, Efficacy
- Medical subject headings
- Hemochromatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm 1: Erythrocyte apheresisProcedure or surgery
Erythrocyte apheresis
Arm 2: Whole blood phlebotomyProcedure or surgery
Traditional whole blood phlebotomy
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Erythrocyte apheresis Receives: Procedure: Arm 1: Erythrocyte apheresis |
| Arm 2 | Active comparator | Phlebotomy Receives: Procedure: Arm 2: Whole blood phlebotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decline in ferritin levels and transferrin saturation
Secondary outcomes (4)
Decline in hemoglobin levels
Patient discomfort during therapeutic procedure
Time consumption
Costs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2007 (estimated)
- Study startJan 2006
- Study completionDec 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HemochromatosisStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 67 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Bergen
- Sponsor type
- University, hospital or other
- Collaborators
- Helse Fonna, Haukeland University Hospital, University Hospital, Akershus
- Investigators
- Tatjana Sundic, MD, Principal investigator, Department of Immunology and Transfusion Medicine, Haugesund HospitalSigbjorn Berentsen, MD, PhD, Study chair, Department of Medicine, Haugesund HospitalTor Hervig, MD, PhD, Study chair, Department of Transfusion Medicine, Haukeland University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00509652
- Sponsor's protocol ID
- NSD13903
- Status last verified
- Jul 2007
- First submitted
- 27 Jul 2007
- Last updated
- 31 Jul 2007
- Results posted
- No
- Data monitoring committee
- No
Publications
Asberg A, Hveem K, Thorstensen K, Ellekjter E, Kannelonning K, Fjosne U, Halvorsen TB, Smethurst HB, Sagen E, Bjerve KS. Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons. Scand J Gastroenterol. 2001 Oct;36(10):1108-15. doi: 10.1080/003655201750422747.
PubMed 11589387Muncunill J, Vaquer P, Galmes A, Obrador A, Parera M, Bargay J, Besalduch J. In hereditary hemochromatosis, red cell apheresis removes excess iron twice as fast as manual whole blood phlebotomy. J Clin Apher. 2002;17(2):88-92. doi: 10.1002/jca.10024.
PubMed 12210712Rombout-Sestrienkova E, van Noord PA, van Deursen CT, Sybesma BJ, Nillesen-Meertens AE, Koek GH. Therapeutic erythrocytapheresis versus phlebotomy in the initial treatment of hereditary hemochromatosis - A pilot study. Transfus Apher Sci. 2007 Jun;36(3):261-7. doi: 10.1016/j.transci.2007.03.005. Epub 2007 Jun 13.
PubMed 17569592Knutsen, H. & Hammerstrom, J. Handlingsprogram for hemokromatose [Norwegian national program for treatment of haemochromatosis]. http://www.legeforeningen.no/asset/22333/1/22333_1.doc . 2003. Norwegian Society of Haematology.
Telset BIV. Behandling av hereditær hemokromatose: fullblodstapping eller erytrocyttaferese? [Treatment of hereditary haemochromatosis: whole blood phlebotomy or red cell apheresis?] Master Thesis. Bergen: Faculty of Medicine, University of Bergen, 2004
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Effect of Erythrocyte Apheresis as Compared to Full Blood Phlebotomy in Patients With Hereditary Hemochromatosis
- ClinicalTrials.gov ID
- NCT00509652
- Acronym / sponsor ID
- NSD13903
- Conditions
- Hemochromatosis
- Keywords
- Hemochromatosis, Primary hemochromatosis, Hereditary hemochromatosis, Therapy, Erythrocyte apheresis, Phlebotomy, Apheresis, Efficacy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 67 participants (estimated)
- Lead sponsor
- University of BergenUniversity, hospital or other
- Collaborators
- Helse Fonna, Haukeland University Hospital, University Hospital, Akershus
- Study start
- Jan 2006
- Study completion
- Dec 2009 (estimated)
- First posted
- 31 Jul 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.
Primary hemochromatosis is the most frequent hereditary condition in Scandinavia. The condition may result in serious organ damage which can be prevented by therapy, but only few patients develop such organ damage. The optimal treatment, therefore, is still a matter of discussion Prevention of organ damage has traditionally been accomplished by drawing of full blood (phlebotomy), which has to be frequently repeated during the initial phase and then continued indefinitely as a maintenance treatment. The removed amount of iron may be increased two- or threefold for each procedure by using modern equipment for selective removal of red blood cells (red cell apheresis). Possible drawbacks of this technique may be higher costs, prolonged time for each therapeutic procedure, and certain requirements to the patients. The possible advantages are the reduced number of therapeutic procedures and less strain for the patient. No larger, randomized study has been published in order to determine which method should be preferred.
This study is a controlled trial in which participating patients are asked to be randomized to red cell apheresis or traditional phlebotomy. Each group will be followed by means of well-defined assessments in order to explore possible advantages and disadvantages of each method in order to establish what type of treatment should be recommended.
Detailed description
Introduction Primary hemochromatosis is the most frequent hereditary condition in Scandinavia. The condition may result in serious organ damage which can be prevented by therapy, but only few patients develop such organ damage. Provided the lack of more exact knowledge of which patients should be treated, we have based our inclusion criteria on the guidelines published by the Norwegian Society of Hematology. However, the criteria for ferritin levels have been set at 300 micrograms/L for patients who are homozygous for the C282Y mutation, and also heterozygous individuals will be included if ferritin is higher than 500 micrograms/L.
Furthermore, the optimal treatment method is still a matter of discussion. Prevention of organ damage has traditionally been accomplished by whole blood phlebotomy, which has to be frequently repeated during the initial phase and then continued indefinitely as a maintenance treatment. The removed amount of iron may be increased two- or threefold for each procedure by using modern equipment for selective withdrawal of red blood cells (erythrocyte apheresis). Possible drawbacks of this technique may be higher costs, prolonged time for each therapeutic procedure, and certain requirements to the patients. The possible advantages are the reduced number of therapeutic procedures and less strain for the patient. No larger, randomized study has been published in order to determine which method should be preferred.
Hypothesis: A more rapid decline of primary endpoints (see below) can be achieved by erythrocyte apheresis as compared to traditional phlebotomy, without significant disadvantages.
Design The trial is prospective, randomized and open. Eligible patients are randomized to erythrocyte apheresis and phlebotomy.
Endpoints Primary endpoints Decline of ferritin levels and transferrin saturation.
Secondary endpoints and other variables to be studied Decline in hemoglobin levels. Discomfort during the therapeutic procedure. Any changes in EVF, blood cell counts or albumin and CRP levels. Certain well-defined financial costs: consumed material, technician working time.
Inclusion criteria
- Diagnosis
- Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%.
- Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%.
- Requirements to the patient Body weight higher than 65 kg and initial hemoglobin level higher than 12 g/dL.
Treatment schedule Following randomization to either apheresis or phlebotomy, patients are treated until ferritin levels have declined to below 50 micrograms/L and they are then followed for one year. Patients randomized to apheresis are treated every second week, whereas patients in the phlebotomy group are treated weekly. Prolongation of the interval is permitted in both groups in case of well-defined clinical indications. Any prolongation is to be recorded along with the clinical indication.
Follow-up Clinical symptoms, body weight, laboratory findings (Hemoglobin levels; blood cell counts; levels of iron, transferrin, ferritin, albumin and IgG; serologic assessments for hepatitis viruses, CMV and HIV), discomfort during the therapeutic procedure, duration of each procedure, costs for consumed material, working time of the technician for each procedure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Procedure: Arm 1: Erythrocyte apheresisErythrocyte apheresis |
| Arm 2 | Active comparator | Procedure: Arm 2: Whole blood phlebotomyPhlebotomy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis
- Requirements to the patient Body weight higher than 65 kg and initial hemoglobin level higher than 12 g/dL.
Key exclusion criteria (3 listed)
- Contra-indications to either treatment modality
- Patients who are not able to co-operate
- Lack of informed consent
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 |
|---|---|---|
| Arm 1: Erythrocyte apheresisErythrocyte apheresis | Procedure or surgery | Arm 1 |
| Arm 2: Whole blood phlebotomyTraditional whole blood phlebotomy | Procedure or surgery | Arm 2 |
Primary outcome
Decline in ferritin levels and transferrin saturation
4 secondary outcomes
Decline in hemoglobin levels
Patient discomfort during therapeutic procedure
Time consumption
Costs
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2007.
- Background: PubMed 11589387Asberg A, Hveem K, Thorstensen K, Ellekjter E, Kannelonning K, Fjosne U, Halvorsen TB, Smethurst HB, Sagen E, Bjerve KS. Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons. Scand J Gastroenterol. 2001 Oct;36(10):1108-15. doi: 10.1080/003655201750422747.
- Background: PubMed 12210712Muncunill J, Vaquer P, Galmes A, Obrador A, Parera M, Bargay J, Besalduch J. In hereditary hemochromatosis, red cell apheresis removes excess iron twice as fast as manual whole blood phlebotomy. J Clin Apher. 2002;17(2):88-92. doi: 10.1002/jca.10024.
- Background: PubMed 17569592Rombout-Sestrienkova E, van Noord PA, van Deursen CT, Sybesma BJ, Nillesen-Meertens AE, Koek GH. Therapeutic erythrocytapheresis versus phlebotomy in the initial treatment of hereditary hemochromatosis - A pilot study. Transfus Apher Sci. 2007 Jun;36(3):261-7. doi: 10.1016/j.transci.2007.03.005. Epub 2007 Jun 13.
- BackgroundKnutsen, H. & Hammerstrom, J. Handlingsprogram for hemokromatose [Norwegian national program for treatment of haemochromatosis]. http://www.legeforeningen.no/asset/22333/1/22333_1.doc . 2003. Norwegian Society of Haematology.
- BackgroundTelset BIV. Behandling av hereditær hemokromatose: fullblodstapping eller erytrocyttaferese? [Treatment of hereditary haemochromatosis: whole blood phlebotomy or red cell apheresis?] Master Thesis. Bergen: Faculty of Medicine, University of Bergen, 2004
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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.
Tatjana Sundic, MD principal investigator
Department of Immunology and Transfusion Medicine, Haugesund Hospital
Sigbjorn Berentsen, MD, PhD study chair
Department of Medicine, Haugesund Hospital
Tor Hervig, MD, PhD study chair
Department of Transfusion Medicine, Haukeland University Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Arm 1: Erythrocyte apheresis and Arm 2: Whole blood phlebotomy in people with Hemochromatosis, run by University of Bergen at 3 sites in Norway.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 31 Jul 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Norway. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tatjana Sundic, MD (+47-52732000, tatjana.sundic@helse-fonna.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decline in ferritin levels and transferrin saturation. 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 NCT00509652, which also lists 5 linked publications.
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 31 Jul 2007.