A randomised, controlled trial of Helicobacter pylori (H.pylori) eradication therapy plus oral iron therapy versus oral iron therapy alone in patients with iron deficiency of obscure origin

A low blood haemoglobin level, known as anaemia, is a common medical condition and is frequently caused by a deficiency in stored iron. Despite close scrutiny of an individual’s history, diet, ability to absorb iron, and both stomach and colon by endoscopy (flexible telescopic examination), no cause is found in a sizable minority (nearly half). Interest has been growing in whether the anaemia in some of these individuals might be caused by the bacterium Helicobacter pylori, which resides in the stomachs of about 40% of Australians. This bacterium can cause stomach and duodenal ulcers, which themselves can bleed and cause iron-deficiency anaemia, and, therefore, this is the principal indication to eradicate it. However, many infected individuals have no bleeding lesion despite being anaemic. In fact, although iron deficiency is usually treated initially with oral iron supplements to replenish stores, studies have suggested that H.pylori might make this treatment less effective. This study, therefore, aims to answer the question of whether H.pylori infection is associated with failure of oral iron to replenish stores and an increased risk of recurrent iron deficiency after a course of oral iron supplements has been completed. We aim to recruit men and post-menopausal women whose history and endoscopies do not explain the cause of their iron-deficiency. Subjects entering the study will all receive a 2 month course of oral iron therapy to replenish stores, as per their usual clinical care. H.pylori status will have been determined in most at the time of gastroscopy. In the remainder it will be determined by a simple blood test. Those who are H.pylori positive will be randomised in a 50:50 fashion to receive either H.pylori eradication therapy or no eradication therapy at the outset. Eradication therapy consists of a week’s course of two antibiotics and an acid-blocking medication (licensed and commercially available as Nexium Hp7). Haemoglobin level and ferritin level (a measure of iron stores) will be assessed by blood test as per the usual clinical care of the patient (i.e. at the end of the course of iron, and then at 2 months, 4 months and 6 months beyond this point). If an individual’s blood test shows persistent or recurrent iron deficiency at any point, he or she will have reached an endpoint and will leave the study. The primary outcome to be studied is the proportion of subjects who develop persistent or recurrent iron deficiency during the 6 months of follow-up. We hypothesise that this proportion will be larger in those with H.pylori who do not receive eradication therapy, compared to those with H.pylori randomised to eradication therapy and those who are H.pylori-negative. Secondary endpoints will include the median fall in ferritin level within each group during follow-up.