Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00495781 |
| Other study ID # |
SFIDS-2004 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
July 2, 2007 |
| Last updated |
July 2, 2007 |
| Start date |
October 2004 |
| Est. completion date |
May 2006 |
Study information
| Verified date |
July 2007 |
| Source |
Spital Zollikerberg |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Switzerland: Kantonale Ethische Kommission, Zürich |
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of the study is to define laboratory parameters which are best suited to
diagnose functional iron deficiency. Functional iron deficiency is a condition where - due
to the lack of iron bioavailability - the patient suffers from symptoms such as fatigue and
weakness, or his/her capacity to produce red blood cells is reduced.
Description:
In dialysis patients the degree of anemia is highly correlated to both morbidity and
mortality. A drop in Hb by 10 g/L translates into an increase in the rate of
hospitalizations of 5 to 6 % and a rise in mortality by 4 to 5 %. The past two decades have
seen great progress in the treatment of renal anemia with the advent of erythropoietin, and,
more recently, darbepoetin. Quite soon, however, it became clear, that anemia in patients
with chronic renal failure is complicated by a lack of bioavailable iron, which confers
these patients partly resistant to treatment with erythropoietin/darbepoetin.
There are several parameters in use to estimate total body iron stores in the diagnosis of
iron deficiency and iron deficiency anemia. Serum iron represents only a minor fraction of
total body iron and is subject to major fluctuations due to influx or efflux from tissue
iron stores. In addition, it shows a great diurnal variability, and is therefore a very poor
parameter of iron deficiency. Iron saturation of its transporter protein in blood,
transferrin, is similarly difficult to interpret, as it depends also in part on the
determination of serum iron levels. Ferritin, the tissue iron storage protein, is released
into the circulation during active liver cell damage, and, quite unlike serum transferrin
levels, ferritin levels rise during the acute phase response of the inflammatory reaction.
In most cases, however, the serum ferritin level, if substantiated by the concurrent
determination of the C-reactive protein and the alanine-leucine-aminotransferase (ALT) to
exclude both, occult liver cell damage and inflammation, correlates well with total body
iron stores and total body iron deficiency, respectively.
The serum ferritin level, however, is a poor marker of functional iron deficiency when
erythropoiesis is inhibited by the relative lack bioavailable iron in high turnover states
of the bone marrow such as in hemolysis and in the thalassemias. Correspondingly, in
patients with hemochromatosis and an increased functional iron availability, erythropoiesis
will be augmented following acute blood losses.
To date no golden standard exists to measure functional iron deficiency in a routine
clinical setting. As a matter of fact, in some clinical studies functional iron deficiency
is still diagnosed indirectly and retrospectively by the effect of an iron substitution
therapy (increase in Hb by 10 g/L following 4 weeks of iron supplementation)
The percentage of hemoglobin–deficient, hypochromic erythrocytes, as measured by some
hemocytometers, reflects the availability of iron for erythropoiesis and has become a
surrogate marker of functional iron deficiency. As the lifespan of erythrocytes varies
according to the degree of the patient’s uremia between approximately 60 and 120 days,
hypochromic erythrocytes, measured as a percentage of total erythrocytes (%-Hypo), become
detectable only late in the course of erythropoietin therapy, and are therefore thought by
some to be of only limited sensitivity in the diagnosis of functional iron deficiency.
With the automated measurement of reticulocytes, it has become now possible on some
hemocytometers, such as the Advia 120, to also determine the hemoglobin content in newly
formed reticulocytes (CHr). The hemoglobin content of reticulocytes mirrors more closely the
current availability of iron for erythropoiesis. What would make CHr so attractive for
clinicians and the clinical laboratory, is not only its acclaimed sensitivity to detect
functional iron deficiency, but, even more so, its easy availability, as it forms part of a
simple reticulocyte count on a normal hemocytometer.
In other hemocytometric systems laser light scatter patterns have been utilized to
characterize the hemoglobin content in reticulocytes (RET-HE). This new parameter, RET-HE,
has been shown to be of a similar sensitivity and specificity as CHr and to give comparable
results in clinical samples (CHr, r = 0.94).
The present study is meant to define the laboratory parameter (%-Hypo/CHr or RET-He) which
is suited best to diagnose functional iron deficiency. The study design asks for the
parameter with which physicians will be able to diagnose their patients so to improve the
management of their anemia. A diagnostic parameter is searched for which improves the
patients' treatment the most, as measured by blood hemoglobin levels (primary end point 1),
at the lowest possible costs (primary end point 2).
