Dataset Information

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

ABSTRACT:

Background

Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women.

Methods

In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up.

Findings

Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34).

Interpretation

In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight.

Funding

Bill & Melinda Gates Foundation (INV-010612).

SUBMITTER: Pasricha SR

PROVIDER: S-EPMC10193370 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

Pasricha Sant-Rayn SR Mwangi Martin N MN Moya Ernest E Ataide Ricardo R Mzembe Glory G Harding Rebecca R Zinenani Truwah T Larson Leila M LM Demir Ayse Y AY Nkhono William W Chinkhumba Jobiba J Simpson Julie A JA Clucas Danielle D Stones William W Braat Sabine S Phiri Kamija S KS

Lancet (London, England) 20230421 10388

<h4>Background</h4>Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women.<h4>Methods</h4>In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Mala ...[more]

PMID: 37088092

Similar Datasets

Project description:BackgroundAnaemia is common in mothers and infants in the first year postpartum, especially in sub-Saharan Africa. We evaluated whether treating anaemia in the second trimester of pregnancy with a single dose of intravenous iron, ferric carboxymaltose, compared with standard-of-care oral iron could alleviate anaemia in postpartum women and their infants.MethodsREVAMP (ACTRN12618001268235), an open-label, individually randomised, controlled trial done across nine urban and five rural health centres in Malawi, recruited women if they were in the second trimester of singleton pregnancy, had a capillary haemoglobin concentration of less than 10·0 g/dL, and had a negative malaria rapid diagnostic test. Once enrolled, women were randomly assigned (1:1) to receive intravenous ferric carboxymaltose (20 mg/kg up to 1000 mg) or standard of care (60 mg oral elemental iron twice daily for 90 days); all women received preventive malaria treatment. The primary endpoint of REVAMP was anaemia prevalence at 36 weeks of gestation, with follow-up of mothers and infants until 1 month postpartum. In REVAMP-EXTENDED, women from REVAMP who gave consent, and their infants, were followed up at 3, 6, 9, and 12 months postpartum, and venous blood was collected for haemoglobin, ferritin, and C-reactive protein measurement. Maternal postpartum outcomes comprised prevalence of anaemia (venous haemoglobin concentration <11 g/dL up to and including delivery and <12·0 g/dL postpartum) and haemoglobin concentration, as well as iron status (iron deficiency, defined as serum ferritin <15 μg/L, or <30 μg/L if C-reactive protein >5 mg/L, and iron deficiency anaemia [both iron deficiency and anaemia]). Infant outcomes comprised cord ferritin concentration, and haemoglobin and ferritin concentrations at 1, 3, 6, 9, and 12 months of age.FindingsBetween Nov 12, 2018, and March 2, 2021, 862 women were randomly assigned in REVAMP, of whom 793 (393 in the ferric carboxymaltose group [376 liveborn infants] and 400 [379 liveborn infants] in the standard-of-care group) provided consent for REVAMP-EXTENDED. At 12 months postpartum, ferritin concentrations were higher (geometric mean ratio 1·47 [95% CI 1·29-1·66], p<0·0001), and prevalence of iron deficiency was lower (prevalence ratio 0·65 [0·48-0·88], p=0·0050), in mothers receiving ferric carboxymaltose than in those receiving standard of care. Anaemia was less common in women who received ferric carboxymaltose than in those who received standard of care at 1 month (prevalence ratio 0·84 [95% CI 0·71-0·98], p=0·027), 3 months (0·75 [0·62-0·91], p=0·0029), and 6 months (0·78 [0·63-0·96], p=0·018) postpartum but not thereafter. There was no evidence of a difference between groups regarding cord ferritin, infant ferritin, or infant haemoglobin concentrations at any timepoint. Benefits on postpartum anaemia were restricted to mothers with baseline iron deficiency.InterpretationFerric carboxymaltose treatment in the second trimester protected women from postpartum anaemia and iron deficiency but did not affect infant haematological or iron status.FundingBill & Melinda Gates Foundation.TranslationFor the Chichewa translation of the abstract see Supplementary Materials section.

Project description:BackgroundIron deficiency anaemia (IDA) is a major health issues and common type of nutritional deficiency worldwide. For IDA treatment, intravenous (IV) iron is a useful therapy.ObjectiveTo determine the efficacy and cost-effectiveness (CE) of intravenous (IV) Ferric Carboxymaltose (FCM) versus IV Iron Sucrose (IS) in treating IDA.Data sourcesElectronic medical record i.e. Cerner® system.Target populationAdults patients with iron deficiency anaemia.Time horizonA 12-month period (01/01/2018-31/12/2018).PerspectiveHamad Medical Corporation (HMC, a public hospital).InterventionIV Ferric Carboxymaltose versus IV Iron Sucrose.Outcome measuresWith regard to responses to treatment i.e., efficacy of treatment with FCM & IS in IDA patients, hemoglobin (Hgb), ferritin, and transferrin saturation (TSAT) levels were the primary outcomes. Additionally, the researchers also collected levels of iron, platelet, white blood cell (WBC), red blood cell (RBC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). The costs i.e. resources consumed (obtained from NCCCR-HMC) and the CE of FCM versus IS were the secondary outcomes.Results of base-case analysisThere was a significant improvement in Hgb, RBC and MCH levels in the IS group than the FCM group. The overall cost of IS therapy was significantly higher than FCM. The medication cost for FCM was approximately 6.5 times higher than IS, nonetheless, it is cheaper in terms of bed cost and nursing cost. The cost effectiveness (CE) ratio illustrated that FCM and IS were significantly different in terms of Hgb, ferritin and MCH levels. Further, Incremental Cost Effectiveness Ratio (ICER) indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes.Results of sensitivity analysisNot applicable.LimitationsThe study did not consider the clinical or humanistic outcome.ConclusionsThe higher cost of FCM versus IS can be offset by savings in healthcare personnel time and bed space. ICER indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes.

Project description:Iron deficiency is the primary cause of anaemia worldwide and is particularly common among children and adolescents. Intravenous (IV) iron therapy is recommended for paediatric patients with certain comorbidities or if oral iron treatment has been unsuccessful. IV ferric carboxymaltose (FCM) has recently been approved by the US Food and Drug Administration for use in children aged > 1 year. This narrative review provides an overview of the available publications on the efficacy and safety of IV FCM in children and adolescents. A literature search using PubMed and Embase yielded 153 publications; 33 contained clinical data or reports on clinical experience relating to IV FCM in subjects < 18 years of age and were included in the review. No prospective, randomised controlled studies on the topic were found. Most publications were retrospective studies or case reports and included patients with various underlying conditions or patients with inflammatory bowel disease. Efficacy data were included in 27/33 publications and improvements in anaemia, and/or iron status parameters were reported in 26 of them. Safety data were included in 25/33 publications and were in line with the adverse events described in the prescribing information.ConclusionThe available publications indicate that IV FCM, a nanomedicine with a unique and distinctive therapeutic profile, is an effective and generally well-tolerated treatment for iron deficiency or iron deficiency anaemia in children and adolescents. Despite the wealth of retrospective evidence, prospective, randomised controlled trials in the paediatric setting are still necessary.What is known• Iron deficiency and iron deficiency anaemia are usually managed using oral iron therapy, but intravenous iron therapy is recommended for certain paediatric patients. • Intravenous ferric carboxymaltose (FCM) has recently been approved in the US for use in children aged > 1 year.What is new• Despite evidence that FCM is effective and generally well tolerated in children and adolescents, so far, only retrospective studies, non-randomised uncontrolled prospective studies, or case reports have been published in full. • There is a strong need for prospective, randomised controlled trials on FCM in the paediatric setting.

Project description:IntroductionAnaemia in pregnancy remains a critical global health problem, affecting 46% of pregnant women in Africa and 49% in Asia. Oral iron therapy requires extended adherence to achieve correction of anaemia and replenishment of iron stores. Ferric carboxymaltose (FCM) is a recently established intravenous iron formulation associated with substantial advantages in safety, speed of delivery and total dose deliverable in a single infusion. We aim to determine whether FCM given once during the second trimester of pregnancy compared with standard oral iron distributed through routine antenatal services is effective and safe for treatment of moderate to severe maternal anaemia in sub-Saharan Africa.Methods and analysisThe randomized controlled trial of the effect of intravenous iron on anaemia in Malawian pregnant women (REVAMP) is a two-arm confirmatory individually randomised trial set in Blantyre and Zomba districts in Malawi. The trial will randomise 862 women in the second trimester of pregnancy with a capillary haemoglobin concentration below 100.0 g/L. The study comprises two arms: (a) intravenous FCM (20 mg/kg up to 1000 mg) given once at randomisation, and (b) standard of care oral iron (65 mg elemental iron two times per day) for 90 days (or the duration of pregnancy, whichever is shorter) provided according to local healthcare practices. Both arms receive sulfadoxine-pyrimethamine as intermittent preventive treatment in pregnancy. The primary outcome is the prevalence of anaemia (Hb <110.0 g/L) at 36 weeks' gestation. Secondary outcomes include birth weight, gestation duration and safety outcomes, including clinical malaria, serious perinatal events and postpartum haematologic and health-related outcomes in the mother and child.Ethics and disseminationEthical approval was granted by the Research Ethics Committee (COMREC P.02/18/2357) in Malawi and the Human Research Ethics Committee (WEHI: 18/02), Melbourne, Australia. The protocol is registered with the Australian and New Zealand Clinical Trials Registry. The results will be shared with the local community that enabled the research, and also to the international fora.Trial registration numberACTRN12618001268235; Pre-results.

Project description:In this multi-centre, prospective, non-interventional study, the effectiveness and tolerance of ferric carboxymaltose (ferinject®; FCM) was tested through use in standard gynaecological practice. In total, data from 273 patients was evaluated. 193 of these patients displayed iron deficiency anaemia (IDA), and 68 had iron deficiency without anaemia (ID). The reasons for the ID/IDA were hypermenorrhoea (HyM) (n = 170), post-partum condition (PP) (n = 53) or another indication (n = 53). The average age of the patients was 40 years old, with 8 % of them being vegetarians. Half of the patients had already been treated for anaemia, primarily with oral iron products (94 %). The primary, serious accompanying symptoms of anaemia were fatigue (72 %), lack of concentration (42 %), pale mucous membranes (42 %), headache (26 %) and sleep disorders (21 %). Only one patient did not show serious symptoms at the start of the study. The most frequent indications for parenteral therapy were the need for rapid iron substitution to reduce symptoms (> 70 %), followed by the lower effectiveness or intolerance of oral products (42 % each) as well as patients not completing the course of treatment with oral products (12 %). Patient information was collected at both the beginning and the end of the observation period, which lasted 15 weeks on average. FCM was most frequently administered via infusion (92 %; average infusion duration 21 minutes). Seven percent of patients received bolus injections. The average total iron dosage per patient was 788.7 mg (median 550 mg; range: 50-3000 mg); the median individual dosage was 500 mg (range: 50-1000 mg). The total dosage was, in most cases, administered through a single application (range: 1-10). Symptoms, blood values (Hb), iron stores (serum-ferritin [S-ferritin]) and transport iron (transferrin saturation [TSAT]) normalised to a large extent. In all subgroups, 92 % of women displayed a marked improvement in all of their symptoms. The average increase in Hb-value in the group as a whole was statistically significant, increasing from 10.5 to 13.0 g/dl. In the group with anaemia, the value increased from 9.9 to 13.3 g/dl, with 80 % of women reaching normal Hb-values. The average S-ferritin value increased by a statistically significant > 70 µg/L from 17.2 to 88.8 µg/l and the value for the TSAT increased from 16.3 % to 22.8 %. Seven patients reported experiencing side effects. None of the results were severe. Overall, as part of this non-interventional study for everyday routine in a gynaecological practice, a rapid improvement in symptoms accompanied by the rectification of iron deficiency and anaemia was shown with low occurrences of mild undesirable events, and therefore the data obtained from controlled clinical studies on the effectiveness and tolerance of intravenous ferric carboxymaltose could be confirmed.

Dataset Information

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

Background

Methods

Findings

Interpretation

Funding

Publications

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets