Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage: study protocol for a randomised controlled trial

Abstract

BackgroundPostpartum haemorrhage can lead to iron deficiency with and without anaemia, the clinical consequences of which include physical fatigue. Although oral iron is the standard treatment, it is often associated with gastrointestinal side effects and poor compliance. To date, no published randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside 1000 with standard medical care on physical fatigue in women with postpartum haemorrhage.Methods/DesignIn a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard medical care. Healthy parturients with a singleton pregnancy will be included within 48 hours after delivery.Participants will complete structured questionnaires that focus on several dimensions of fatigue and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal Depression Scale and the Postpartum Questionnaire), at inclusion and at follow-up visits after three days, one week, three weeks, eight weeks, and 12 weeks postpartum. The primary endpoint is the aggregated change in physical fatigue score within 12 weeks postpartum, as measured by a subscale of the Multidimensional Fatigue Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant difference between the mean scores at 1.8, and the assumed standard deviation at 4.2. Hence, 87 participants per treatment group are needed in order to demonstrate superiority; to provide an extra margin for missing data and dropouts, 200 women will be included.DiscussionThe study will provide evidence on relevant clinical outcomes beyond biochemical parameters for intravenous iron isomaltoside 1000 compared to standard medical care in women after postpartum haemorrhage.Trial registrationThis trial is registered with Clinicaltrials.gov (identifier: NCT01895218) on 26 June 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/1745-6215-16-5) contains supplementary material, which is available to authorized users.

A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia

“…For all biochemical efficacy parameters measured (Hb, s‐ ferritin, TSAT, and s‐ iron), faster and/or greater improvements were found with iron isomaltoside compared to iron sucrose. These findings are in agreement with previous trials with iron isomaltoside reporting efficacy in significantly increasing iron related parameters …”

“…It is the matrix structure that enables a controlled and slow release of iron to iron‐binding proteins, avoiding potential toxicity from release of labile iron . Previous published data demonstrate good safety and efficacy of iron isomaltoside in different populations with different comparators . A previous trial compared efficacy of ferric carboxymaltose versus iron sucrose in IBD patients, and iron isomaltoside has been compared with iron sucrose in CKD .…”

Postpartum fatigue, self-care power of women and related factors

“…Literatürde aneminin fiziksel yorgunluğu artırdığı bilgisi yer almakta idi (49,50) . Bu çalışmada, literatürde yer alan bilgilerin aksine, tedavi gerektirecek aneminin varlığı ile yorgunluk arasında herhangi bir ilişki bulunmazken, aneminin varlığında öz-bakım gücü-nün artığı sonucu elde edilmiştir.…”

Iron status and choice of iron therapy during pregnancy: advantages and disadvantages

“…61 Currently available iron carbohydrate preparations for IV iron treatment are based on six compounds: iron sucrose (IS), ferric gluconate, ferric carboxymaltose (FCM), iron dextran (high-and low-molecular-weight dextran), iron isomaltoside and ferumoxytol. 62 Sodium ferric gluconate, IS, and FCM do not contain dextran or any dextran derivatives and thus do not crossreact with anti-dextran antibodies in vitro. 63 IS belongs to the iron complexes of the half robust and medium strong type (molecular mass between 30,000 and 100,000 Da), which after IV administration, deliver the complexed iron from the serum to endogenous ironbinding proteins with a half-life of 90 min.…”