Primary Objective to show that PPIs compared to placebo are an effective treatment of secondary hemochromatosis in a relative large number of patients with hereditary anemia and mild iron overload. Secondary Objectives: To assess the safety and side…
ID
Source
Brief title
Condition
- Haematological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoint of this study, which formed the basis for statistical power
calculations, is the change in LIC from baseline measurements measured by MRI
of the liver after one year of treatment with esomeprazole compared to the
change in LIC from baseline during one year treatment with placebo. The LIC
will be expressed in mg Fe/g dw after data analysis of the T2* and T1 images of
the MRI.
Secondary outcome
1. Tolerability of esomeprazole: the incidence of side effect / adverse events
will be monitored every 3 months during study visits. Measurement of vitamin
B12, zinc and magnesium, T0, T12 and T24. Report of airway infections.
2. Quality of life: this will be assessed with EQ5D-forms, with time intervals
of 3 months.
3. Cost-effectiveness analysis of esomeprazole in treatment of iron overload in
hereditary anemia. This will be assessed by a prospective cost-effectiveness
analysis. IMCQ and iPCQ questionnaires will be filled in with time intervals of
3 months.
4. Related changes in markers of iron metabolism:
a. Plasma hepcidin T0.
b. Serum ferritin T0, T12, T24.
5. Compliance to study drug
a. Plasma gastrin T0, T6, T12, T18, T24.
b. Counting of the capsules.
6. Need for chelation therapy
Background summary
The number one cause of years lived with anemia in Western Europe is hereditary
anemia. The major cause of morbidity and mortality in patients with hereditary
anemia not requiring chronic blood transfusion is iron overload caused by
increased uptake from the gut. Iron overload and hereditary anemia are a
growing, underestimated emerging health care problem. Many patients on iron
chelation therapy, including deferasirox (currently the most frequently used
iron chelating agent) experience side effects such as gastro-intestinal
problems and less frequently renal or hepatic failure. Not including the
economic costs and loss of quality of life caused by side effects of iron
chelation, the cost of prescription alone amounted about 5 million euros in
2014 in the Netherlands. Dietary uptake of iron can be reduced by gastric acid
reduction. Observational studies suggest that PPIs reduce iron uptake. In a
recent randomized controlled trial in hereditary hemochromatosis PPIs
diminished the needed number of phlebotomies. Although, results of this trial
cannot be extrapolated completely to patients with hereditary anemia, this is a
strong suggestion for effectiveness in patients with hereditary anemia*s and
secondary hemosiderosis. A safer alternative for the iron chelators would make
it possible to intervene earlier in these patients at lower costs. Especially
in low-income regions of the world, PPIs could be a life saving and affordable
alternative to prevent and treat iron loading.
Study objective
Primary Objective to show that PPIs compared to placebo are an effective
treatment of secondary hemochromatosis in a relative large number of patients
with hereditary anemia and mild iron overload.
Secondary Objectives:
To assess the safety and side effects of treatment with esomeprazole.
To assess quality of life during treatment with esomeprazole compared with
placebo.
To evaluate cost-effectiveness of esomeprazole in treatment of iron overload in
hereditary anemia.
To assess the changes in *iron markers* during treatment with esomeprazole
compared with placebo.
To assess the need for chelation therapy after one year of treatment with
esomeprazole compared with placebo.
To assess the adherence to therapy in a real life setting.
Study design
Randomised placebo controlled trial with crossover design.
Intervention
12 months treatment with esomeprazole 40 mg twice daily, 12 months treatment
with placebo twice dialy.
Study burden and risks
Follow-up visits, blood sampling and MRI planning are all according to current
clinical guidelines. Extra blood (gastrin and hepcidin analysis) will be taken.
Every 3 months three questionnairies will be filled in to assess quality of
life and cost-effectiviness. Extent of the burden will be minimal on top of the
standard treatment protocol, besides the daily intake of two capsules.
Safety of esomeprazole treatment is one of the most important outcomes of the
study. We will monitor the side effects / adverse events every visit. Extra
visits or contact moments will be planned if necessary in case of adverse
events. Special attention should be paid to interactions with other drugs as
outlined in paragraph 12.1.h of METC protocol.
In our opinion, the potential benefit of esomeprazole outweighs the possible
risks of this trial. Currently the only treatment option for iron overload is
iron chelation therapy with potential toxic effects and severe side effects.
Esomeprazole is generally considered as a medicament with an excellent safety
profile. Therefore we consider the possible risks for the patients as
acceptable.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
o Diagnosis of hereditary anemia: hemoglobinopathy (including all sickle cell syndromes and beta-thalassemia), sideroblastic anemia, congenital dyserythropoietic anemia or an erythrocyte enzyme deficiency.
o Hemoglobin before study inclusion <7.0 mmol/L
o Clinically stable and relevant iron overload defined as either one of:
- a baseline LIC measurement by MRI between 3 and 15 mg Fe/g without having received iron chelation 2 months prior to entering the study.
- OR a baseline LIC measurement by MRI between 3 and 15 mg Fe/g on stable chelation therapy (deferasirox, deferoxamine or deferiprone), with documented stable dosage the preceding 2 months and no expected dose reductions or increases the next two years.
o Aged more than 18 years and able to sign informed consent.
o Received less than 10 units of blood during the preceding 12 months.
o Is expected to receive less than 4 units fo blood during the following 12 months
o Is not splenectomized during the preceding 24 months.
Exclusion criteria
o Pregnancy.
o Liver cirrhosis.
o Heart failure.
o Severe cardiac iron overload defined as MRI T2* < 20 ms.
o Severe liver iron overload defined as MRI LIC > 15 mg Fe/g dw.
o Expected poor compliance.
o Currently taking PPI and not able to stop for personal or medical reasons.
o Patients that are being phlebotomized as treatment for iron overload.
o Current peptic ulcer disease, gastro-intestinal bleeding or other causes of blood loss.
o Contra-indication for esomeprazole use.
o Concomitant use of clopidogrel.
o Contra-indication for MRI.
o Received more than 4 units blood during one of the treatment periods of 12 months.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003777-34-NL |
| CCMO | NL63198.041.17 |