Gasche 2015.

Methods	Phase III, RCT, double‐blinded
Participants	Crohn's disease or ulcerative colitis, in remission or mild‐to‐moderate disease activity (CDAI < 220; SCCAI < 4). All required to have a mild‐to‐moderate iron‐deficiency anaemia (IDA) (Hb concentration ≥ 9.5 g/dL and < 12.0 g/dL for females and ≥ 9.5 g/dL and < 13.0 g/dL for males and serum ferritin levels < 30 ug/L) and previously failed on treatment with oral ferrous products (OFP). Participants receiving protocol‐allowed immunosuppressive and immunomodulatory agents at screening were required to have been on a stable dose for ≥ 4 weeks before randomisation. Exclusion criteria: patients with anaemia unrelated to iron deficiency or who had received depot iron preparations, erythropoietin, or blood transfusions within 12 weeks of screening; oral iron treatment within 4 weeks of randomisation; treatment with immunosuppressants known to induce anaemia; folate deficiency; uncorrected vitamin B12 deficiency; serum creatinine > 2.0 mg/dL (176 ųmol/L); abnormal liver function tests and pregnancy A total of 128 participants were randomised to the ferric maltol group (n = 64) or placebo group (n = 64) Age [Mean(SD) years]: ferric maltol group 40.1 (13.5); placebo group 38.5 (12.3) Gender: ferric maltol group (24 males, 40 females); placebo group (21 males, 43 females) Disease type: ferric maltol group (35 CD, 29 UC); placebo group (35 CD, 29 UC) Disease duration [Mean(SD) years]: ferric maltol group UC 9.0 (8.28)/CD 11.25 (9.3); placebo group UC 10.99 (11.43)/CD 11.01 (8.09) (author information) Loss to follow‐up: n = 20 in total. Ferric maltol group (n = 9); due to adverse event (n = 5), participant withdrawal (n = 3), physician decision (n = 1); Placebo group (n = 11); due to adverse event (n = 4), protocol violation (n = 1), participant withdrawal (n = 5), physician decision (n = 1)
Interventions	Ferric maltol Dosing regimen: 231.5 mg of ferric maltol (equivalent to 30 mg of elemental iron) twice daily Mode of delivery: Oral Duration: 12 weeks Setting of trial: 4 centres in Austria, Germany, Hungary and the UK Setting of intervention: IBD clinic (author information) Comparision treatment: Placebo ‐ the capsules had the same excipients as ferric maltol without the active ingredient (author information) Co‐interventions: Study participants did not receive any additional co‐interventions during the trial, apart from the ones they were already on (author information).
Outcomes	Fatigue was assessed using the SF‐36 vitality subscale. Quality of life was assessed using the SF‐36 and the IBDQ. Adverse events were recorded according to MedDRA preferred terms. Treatment‐emergent adverse events assessed were the following: abdominal pain, diarrhoea, constipation, nasopharyngitis, flatulence, abdominal discomfort, rectal haemorrhage, arthralgia, abdominal distension, gastroesophageal reflux disease, fatigue, worsening of CD, headache, worsening of UC, vomiting, upper respiratory tract infection, oropharyngeal pain, Hb decreased, seasonal allergy, pruritis, nausea Other outcomes assessed: change in Hb concentration; serum ferritin concentration; percentage transferrin saturation (TSAT); clinical symptoms (SCCAI; CDAI) Assessment time points: Randomisation (baseline) and week 12
Notes	Funders were Iron Therapeutics (UK) Ltd, now Shield TX (UK) Ltd (author information). Additional information was supplied by the author. Data analysed with intention‐to‐treat analyses
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation codes were used to randomise participants. Generation of randomisation codes and drug packaging were performed by independent providers (ALMAC, AXIO and Piramal, respectively). The subject and kit randomisation lists were generated using Statistical Analysis System (SAS) v9.2 (author information).
Allocation concealment (selection bias)	Low risk	"Randomisation to either ferric maltol or placebo was conducted through an interactive voice response system (IXRS system ‐ author information) according to a centralised randomisation list".
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Patients and all sponsors, clinical research and clinical staff were blinded to the randomisation code until all randomized trial processes were complete".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The investigators and participants were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Loss to follow‐up similar in the intervention (n = 9) and control groups (n = 11) and reasons comparable
Selective reporting (reporting bias)	Low risk	All information on outcomes were transparent and outcomes assessed were reported.
Other bias	Low risk	Baseline demographics and disease characteristics were generally comparable between the intervention and control groups.