Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT00509652
Other study ID # NSD13903
Secondary ID
Status Recruiting
Phase N/A
First received July 27, 2007
Last updated July 27, 2007
Start date January 2006
Est. completion date December 2009

Study information

Verified date July 2007
Source University of Bergen
Contact Tatjana Sundic, MD
Phone +47-52732000
Email tatjana.sundic@helse-fonna.no
Is FDA regulated No
Health authority Norway:National Committee for Medical and Health Research EthicsNorway: Norwegian Social Science Data Services
Study type Interventional

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 67
Est. completion date December 2009
Est. primary completion date
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 70 Years
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Procedure:
Arm 1: Erythrocyte apheresis
Erythrocyte apheresis
Arm 2: Whole blood phlebotomy
Traditional whole blood phlebotomy

Locations

Country Name City State
Norway Haukeland University Hospital, Department of Transfusion Medicine Bergen
Norway Haugesund Hospital, Department of Immunology and Transfusion Medicine Haugesund
Norway Akershus University Hospital (AHUS), Department of Transfusion Medicine Nordbyhagen

Sponsors (4)

Lead Sponsor Collaborator
University of Bergen Haukeland University Hospital, Helse Fonna, University Hospital, Akershus

Country where clinical trial is conducted

Norway, 

References & Publications (5)

Asberg A, Hveem K, Thorstensen K, Ellekjter E, Kannelønning K, Fjøsne 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. — View Citation

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.

Muncunill J, Vaquer P, Galmés 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. — View Citation

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. Epub 2007 Jun 13. — View Citation

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

Outcome

Type Measure Description Time frame Safety issue
Primary Decline in ferritin levels and transferrin saturation
Secondary Decline in hemoglobin levels
Secondary Patient discomfort during therapeutic procedure
Secondary Time consumption
Secondary Costs
See also
  Status Clinical Trial Phase
Completed NCT00199628 - Research Network for Neonatal Diseases Induced by Tissular Fetomaternal Alloimmunization
Completed NCT03654794 - Study of the Cellular Diffusion of Tacrolimus Across the Membrane of Mononuclear Cells
Terminated NCT00122980 - Stroke With Transfusions Changing to Hydroxyurea Phase 3
Completed NCT00202436 - Haemochromatosis:Phlebotomy Versus Erythrocytapheresis Therapy Phase 3
Withdrawn NCT01892644 - Treatment of Iron Overload With Deferasirox (Exjade) in Hereditary Hemochromatosis and Myelodysplastic Syndrome Phase 2
Not yet recruiting NCT01524757 - Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis N/A
Completed NCT00349453 - Study Using Deferiprone Alone or in Combination With Desferrioxamine in Iron Overloaded Transfusion-dependent Patients Phase 2
Recruiting NCT03743272 - Repeatability and Reproducibility of Multiparametric MRI
Recruiting NCT06137079 - "Iron Overload and Endocrinological Diseases"
Completed NCT00712738 - Oral Nifedipine to Treat Iron Overload Phase 1
Completed NCT00001455 - Iron Overload in African Americans N/A
Completed NCT00006312 - Hemochromatosis--Genetic Prevalence and Penetrance N/A
Completed NCT00005559 - Statistical Basis for Hemochromatosis Screening N/A
Completed NCT00350662 - Study With Deferiprone and/or Desferrioxamine in Iron Overloaded Patients Phase 3
Completed NCT00005541 - Hemochromatosis and Iron Overload Screening Study (HEIRS) N/A
Completed NCT00000595 - Evaluation of Subcutaneous Desferrioxamine as Treatment for Transfusional Hemochromatosis Phase 2
Completed NCT04631718 - MRI QSM Imaging for Iron Overload
Active, not recruiting NCT00007150 - Treatment of Hemochromatosis Phase 2
Completed NCT00587535 - Evaluation of a New MR Pulse Sequence to Quantify Liver Iron Concentration N/A
Enrolling by invitation NCT02025543 - Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content