PPI in secondary hemochromatosis.

Rationale: 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.


Objective: to show that PPIs are an effective and safe treatment of secondary hemochromatosis in patients with hereditary anemia and mild iron overload.


Study design: randomised placebo controlled cross-over trial.


Study population: 40 non-transfusion-dependent patients (adults) with a form of hereditary anemia with mild to moderate iron overload. Mild to moderate iron overload is defined as a baseline LIC (liver iron content) between 3 and 15 mg Fe/g dry weight (dw) without iron chelation therapy or on stable chelation therapy.


Intervention: 12 months treatment with esomeprazole 40 mg twice daily or 12 months treatment with placebo twice daily.


Primary endpoint: the change in LIC measured by MRI of the liver expressed in mg Fe/g dw after one year of treatment with esomeprazole compared to treatment with placebo.

We hypothesize that proton pump inhibitors are an effective and safe treatment of secondary hemochromatosis in patients with hereditary anemia and mild iron overload.

MRI liver will be performed at baseline, T= 12 months and T= 24 months.

12 months treatment with esomeprazole 40 mg twice daily or 12 months treatment with placebo twice daily.