PMID- 36880049
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230322
IS  - 2589-5370 (Electronic)
IS  - 2589-5370 (Linking)
VI  - 56
DP  - 2023 Feb
TI  - A novel nano-iron supplement versus standard treatment for iron deficiency 
      anaemia in children 6-35 months (IHAT-GUT trial): a double-blind, randomised, 
      placebo-controlled non-inferiority phase II trial in The Gambia.
PG  - 101853
LID - 10.1016/j.eclinm.2023.101853 [doi]
LID - 101853
AB  - BACKGROUND: Iron deficiency anaemia (IDA) is the leading cause of years lost to 
      disability in most sub-Saharan African countries and is especially common in 
      young children. The IHAT-GUT trial assessed the efficacy and safety of a novel 
      nano iron supplement, which is a dietary ferritin analogue termed iron hydroxide 
      adipate tartrate (IHAT), for the treatment of IDA in children under 3 years of 
      age. METHODS: In this single-country, randomised, double-blind, parallel, 
      placebo-controlled, non-inferiority Phase II study in The Gambia, children 6-35 
      months with IDA (7</=Hb < 11 g/dL and ferritin<30 mug/L) were randomly assigned 
      (1:1:1) to receive either IHAT, ferrous sulphate (FeSO(4)) or placebo daily for 3 
      months (85 days). The daily iron dose was 12.5 mg Fe equivalent for FeSO(4) and 
      the estimated dose with comparable iron-bioavailability for IHAT (20 mg Fe). The 
      primary efficacy endpoint was the composite of haemoglobin response at day 85 and 
      correction of iron deficiency. The non-inferiority margin was 0.1 absolute 
      difference in response probability. The primary safety endpoint was 
      moderate-severe diarrhoea analysed as incidence density and prevalence over the 3 
      months intervention. Secondary endpoints reported herein include hospitalisation, 
      acute respiratory infection, malaria, treatment failures, iron handling markers, 
      inflammatory markers, longitudinal prevalence of diarrhoea and incidence density 
      of bloody diarrhoea. Main analyses were per-protocol (PP) and intention-to-treat 
      (ITT) analyses. This trial is registered with clinicaltrials.gov (NCT02941081). 
      FINDINGS: Between Nov 2017 and Nov 2018, 642 children were randomised into the 
      study (214 per group) and included in the ITT analysis, the PP population 
      included 582 children. A total of 50/177 (28.2%) children in the IHAT group 
      achieved the primary efficacy endpoint, as compared with 42/190 (22.1%) in the 
      FeSO(4) group (OR 1.39, 80% CI 1.01-1.91, PP population) and with 2/186 (1.1%) in 
      the placebo group. Diarrhoea prevalence was similar between groups, with 40/189 
      (21.2%) children in the IHAT group developing at least one episode of 
      moderate-severe diarrhoea over the 85 days intervention, compared with 47/198 
      (23.7%) in the FeSO(4) group (OR 1.18, 80% CI 0.86-1.62) and 40/195 (20.5%) in 
      the placebo group (OR 0.96, 80% CI 0.7-1.33, PP population). Incidence density of 
      moderate-severe diarrhoea was 2.66 in the IHAT group and 3.42 in the FeSO(4) 
      group (RR 0.76, 80% CI 0.59-0.99, CC-ITT population).There were 143/211 (67.8%) 
      children with adverse events (AEs) in the IHAT group, 146/212 (68.9%) in the 
      FeSO(4) group and 143/214 (66.8%) in the placebo group. There were overall 213 
      diarrhoea-related AEs; 35 (28.5%) cases reported in the IHAT group compared with 
      51 (41.5%) cases in the FeSO(4) group and 37 (30.1%) cases in the placebo group. 
      INTERPRETATION: In this first Phase II study conducted in young children with 
      IDA, IHAT showed sufficient non-inferiority compared to standard-of-care FeSO(4), 
      in terms of ID correction and haemoglobin response, to warrant a definitive Phase 
      III trial. In addition, IHAT had lower incidence of moderate-severe diarrhoea 
      than FeSO(4), with no increased adverse events in comparison with placebo. 
      FUNDING: The Bill & Melinda Gates Foundation (OPP1140952).
CI  - (c) 2023 The Authors.
FAU - Mohammed, Nuredin I
AU  - Mohammed NI
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
FAU - Wason, James
AU  - Wason J
AD  - MRC Biostatistics Unit, Institute of Public Health, University of Cambridge, 
      Cambridge, CB2 0SR, UK.
AD  - Population Health Sciences Institute, Newcastle University, Newcastle, NE2 4BN, 
      UK.
FAU - Mendy, Thomas
AU  - Mendy T
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
FAU - Nass, Stefan A
AU  - Nass SA
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
AD  - Medical Humanities, Amsterdam-UMC - VUmc Location, Vrije Universiteit, Amsterdam, 
      the Netherlands.
FAU - Ofordile, Ogochukwu
AU  - Ofordile O
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
FAU - Camara, Famalang
AU  - Camara F
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
FAU - Baldeh, Bakary
AU  - Baldeh B
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
FAU - Sanyang, Chilel
AU  - Sanyang C
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
FAU - Jallow, Amadou T
AU  - Jallow AT
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
FAU - Hossain, Ilias
AU  - Hossain I
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
FAU - Faria, Nuno
AU  - Faria N
AD  - Department of Veterinary Medicine, University of Cambridge, Madingley Road, 
      Cambridge, CB3 0ES, UK.
FAU - Powell, Jonathan J
AU  - Powell JJ
AD  - Department of Veterinary Medicine, University of Cambridge, Madingley Road, 
      Cambridge, CB3 0ES, UK.
FAU - Prentice, Andrew M
AU  - Prentice AM
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
FAU - Pereira, Dora I A
AU  - Pereira DIA
AD  - Medical Research Council Unit The Gambia at the London School of Hygiene & 
      Tropical Medicine, Banjul, Gambia.
AD  - Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, 
      CB2 1QP, UK.
LA  - eng
SI  - ClinicalTrials.gov/NCT02941081
GR  - MC_UU_00002/6/MRC_/Medical Research Council/United Kingdom
GR  - MR/R005699/1/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_00026/3/MRC_/Medical Research Council/United Kingdom
GR  - MC_U123292699/MRC_/Medical Research Council/United Kingdom
GR  - MR/R010161/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20230209
PL  - England
TA  - EClinicalMedicine
JT  - EClinicalMedicine
JID - 101733727
PMC - PMC9985047
OTO - NOTNLM
OT  - Anaemia
OT  - Children
OT  - Clinical trial
OT  - Iron deficiency
OT  - Iron hydroxide adipate tartrate (IHAT)
OT  - Iron supplementation
OT  - Phase II
COIS- D.I.A.P., N.F. and J.J.P. are inventors of the IHAT iron supplementation 
      technology, for which they could receive future awards to inventors through the 
      MRC Awards to Inventor scheme. They are also scientific advisors to Nemysis Ltd, 
      who now hold the license for IHAT. They have received honoraria or consultancy 
      fees from some or all of: Vifor Pharma UK, Shield Therapeutics, Entia Ltd, Danone 
      Nutricia, UN Food and Agriculture Organisation (FAO) and Nemysis Ltd, for work 
      concerning iron in health. D.I.A.P. has since moved to full employment in the 
      iron and health industry with Vifor Pharma UK but all work pertaining to this 
      publication was conducted whilst at the University of Cambridge and MRC Unit The 
      Gambia at LSHTM. Nemysis Ltd paid consulting fees to J.W.'s Institution. 
      Notwithstanding, the authors declare no potential conflicts of interest with 
      respect to the research, authorship, and/or publication of this article.
EDAT- 2023/03/08 06:00
MHDA- 2023/03/08 06:01
PMCR- 2023/02/09
CRDT- 2023/03/07 02:01
PHST- 2021/10/05 00:00 [received]
PHST- 2023/01/15 00:00 [revised]
PHST- 2023/01/18 00:00 [accepted]
PHST- 2023/03/07 02:01 [entrez]
PHST- 2023/03/08 06:00 [pubmed]
PHST- 2023/03/08 06:01 [medline]
PHST- 2023/02/09 00:00 [pmc-release]
AID - S2589-5370(23)00030-5 [pii]
AID - 101853 [pii]
AID - 10.1016/j.eclinm.2023.101853 [doi]
PST - epublish
SO  - EClinicalMedicine. 2023 Feb 9;56:101853. doi: 10.1016/j.eclinm.2023.101853. 
      eCollection 2023 Feb.