Erythrocyte Apheresis Versus Phlebotomy in Hemochromatosis

NCT ID: NCT00509652

Last Updated: 2007-07-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2009-12-31

Brief 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. 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

1. Diagnosis

1. 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%.

2. Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%.

2. 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

Keywords

Hemochromatosis; Primary hemochromatosis; Hereditary hemochromatosis; Therapy; Erythrocyte apheresis; Phlebotomy; Apheresis; Efficacy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Erythrocyte apheresis

Group Type: EXPERIMENTAL

Arm 1: Erythrocyte apheresis

Intervention Type: PROCEDURE

Erythrocyte apheresis

Arm 2

Phlebotomy

Group Type: ACTIVE_COMPARATOR

Arm 2: Whole blood phlebotomy

Intervention Type: PROCEDURE

Traditional whole blood phlebotomy

Interventions

Arm 1: Erythrocyte apheresis

Erythrocyte apheresis

Intervention Type: PROCEDURE

Arm 2: Whole blood phlebotomy

Traditional whole blood phlebotomy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. 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%.

2. Requirements to the patient Body weight higher than 65 kg and initial hemoglobin level higher than 12 g/dL.

Exclusion Criteria

1. Contra-indications to either treatment modality

2. Patients who are not able to co-operate

3. Lack of informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helse Fonna

OTHER

Sponsor Role: collaborator

Haukeland University Hospital

OTHER

Sponsor Role: collaborator

University Hospital, Akershus

OTHER

Sponsor Role: collaborator

University of Bergen

OTHER

Sponsor Role: lead

Principal Investigators

Tatjana Sundic, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Immunology and Transfusion Medicine, Haugesund Hospital

Sigbjorn Berentsen, MD, PhD

Role: STUDY_CHAIR

Department of Medicine, Haugesund Hospital

Tor Hervig, MD, PhD

Role: STUDY_CHAIR

Department of Transfusion Medicine, Haukeland University Hospital

Locations

Haukeland University Hospital, Department of Transfusion Medicine

Bergen, , Norway

Site Status: RECRUITING

Haugesund Hospital, Department of Immunology and Transfusion Medicine

Haugesund, , Norway

Site Status: RECRUITING

Akershus University Hospital (AHUS), Department of Transfusion Medicine

Nordbyhagen, , Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Tatjana Sundic, MD

Role: CONTACT

Phone: +47-52732000

Email: tatjana.sundic@helse-fonna.no

Sigbjorn Berentsen, MD, PhD

Role: CONTACT

Phone: +47-52732000

Email: s.beren@online.no

Facility Contacts

Tor Hervig, MD, PhD

Role: primary

Signe Hannisdahl

Role: backup

Tatjana Sundic, MD

Role: primary

Sigbjorn Berentsen, MD, PhD

Role: backup

Richard W Olaussen, MD

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 11589387 (View on PubMed)

Muncunill 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.

Reference Type: BACKGROUND

PMID: 12210712 (View on PubMed)

Rombout-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.

Reference Type: BACKGROUND

PMID: 17569592 (View on PubMed)

Knutsen, 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.

Reference Type: BACKGROUND

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

Reference Type: BACKGROUND

Other Identifiers

NSD13903

Identifier Type: -

Identifier Source: org_study_id