Proton pump inhibition for secondary hemochromatosis in hereditary anemia, a phase III placebo controlled randomized cross-over clinical trial.

Phase 3

Completed

Conditions: Hemochromatosis
iron loading.
10018849

Registration Number: NL-OMON48585

Lead Sponsor: niversitair Medisch Centrum Utrecht

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 30

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The main endpoint of this study, which formed the basis for statistical power<br /><br>calculations, is the change in LIC from baseline measurements measured by MRI<br /><br>of the liver after one year of treatment with esomeprazole compared to the<br /><br>change in LIC from baseline during one year treatment with placebo. The LIC<br /><br>will be expressed in mg Fe/g dw after data analysis of the T2* and T1 images of<br /><br>the MRI. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. Tolerability of esomeprazole: the incidence of side effect / adverse events<br /><br>will be monitored every 3 months during study visits. Measurement of vitamin<br /><br>B12, zinc and magnesium, T0, T12 and T24. Report of airway infections.<br /><br>2. Quality of life: this will be assessed with EQ5D-forms, with time intervals<br /><br>of 3 months.<br /><br>3. Cost-effectiveness analysis of esomeprazole in treatment of iron overload in<br /><br>hereditary anemia. This will be assessed by a prospective cost-effectiveness<br /><br>analysis. IMCQ and iPCQ questionnaires will be filled in with time intervals of<br /><br>3 months.<br /><br>4. Related changes in markers of iron metabolism:<br /><br>a. Plasma hepcidin T0.<br /><br>b. Serum ferritin T0, T12, T24.<br /><br>5. Compliance to study drug<br /><br>a. Plasma gastrin T0, T6, T12, T18, T24.<br /><br>b. Counting of the capsules.<br /><br>6. Need for chelation therapy</p><br>