Guide
Oral iron maltol (Ferric Maltol) is a non-salt preparation of iron that can be used as an alternative to iron supplementation therapy, with less gastrointestinal response to oral maltol iron supplementation than other oral iron supplementation therapy. In 2019, it was approved for marketing by the US Food and Drug Administration to treat iron deficiency anemia in inflammatory bowel disease.
In late May 2021, the U.S. research team published an article in AJKD stating that oral iron maltol will help patients with iron deficiency renal anemia and can alleviate iron deficiency anemia in these patients.
Research design
The trial was a multicenter, double-blind, randomized, open-label, placebo-controlled Phase 3 clinical trial conducted at 30 centers in the United States. Patients included in the trial were divided into iron maltol group and control group according to a 2:1 ratio, and in the double-blind phase, the iron maltol group took the maltol group 30 mg bid, while the control group took a placebo, and both groups took 16 weeks. Subgroup stratification was based on iron reserves (ferritin ≤250 or >250 ng/ml) and estimated glomerular filtration rate (eGFR≤30 or >30 ml/min/1.73 m2). After 16 weeks, the research team followed up with open labels until week 52.
In addition, if there is a drug-related adverse reaction, the patient is not allowed to start treatment again.
The primary efficacy endpoint of the trial was a subgroup analysis of population haemoglobin changes from baseline to week 16 and subgroup analysis of renal function (eGFR≤30 or >30 ml/min/1.73 m2) and iron reserves (ferritin ≤250 or >250 ng/ml).
Secondary efficacy endpoints included ratios including at least 1 g/dL and at least 2 g/dL of hemoglobin elevation at week 16; Proportion of patients with a hemoglobin concentration of at least 11.0 g/dL at week 16; Changes in hemoglobin concentration from baseline to weeks 4 and 8; Changes in ferritin, transferrin saturation (TSAT), and serum iron content.
All adverse reactions that occurred during both double-blind and post-open-label follow-up were recorded to assess tolerance.
Research results
Between December 2016 and October 2018, a total of 363 patients were enrolled, but only 167 patients were included in the trial and randomized, with a total of 111 cases in the maltol iron group and 56 cases in the control group. Their baseline information is shown in the table below (Table 1).
In terms of primary efficacy endpoints, the hemoglobin of the maltol ferric group increased significantly compared with the control group, with a least squares mean difference (standard deviation) of 0.5 (0.2) g/dL (95% CI, 0.1-0.9; P=0.01), and specifically, the mean ± standard deviation (SD) of hemoglobin in the maltol ferritoglobin group was 0.6±1.2 g/dL, and -0.1±1.0 g/dL in the placebo group. The subgroup analysis is shown in the table below (Table 2).
In terms of secondary efficacy endpoints, at week 16, 22 patients in the ferromal group (20%) and 5 patients (9%) in the control group had an increase in haemoglobin by at least 1 g/dL; 7 of the 22 patients in the iron maltol group (6% of the ferrornoc group) increased by at least 2 g/dL, while no patients in the placebo group increased by 2 g/dL.
At week 16, haemoglobin concentrations of 30 (27%) patients in the iron maltol group and 7 patients (13%) in the placebo group ≥ 11 g/dL.
From baseline to week 16, ferritin, TSAT, and serum iron increased in patients in the maltol iron group, but decreased in the control group.
In terms of safety, at week 16, adverse events resulted in 7 (6%) patients in the iron maltol group and 5 (9%) patients in the control group withdrew from the trial. Of all adverse events, there were 75 cases (68%) in the iron maltol group and 42 cases (75%) in the control group. The most common adverse reaction was gastrointestinal dysfunction (41% of the iron maltol group, 30% of the control group). After that, the researchers continued to follow up to 52 weeks, with a total of 11 patients (9 percent) withdrawing from the trial during the open-label follow-up due to adverse effects.
summary
Overall, iron maltol, ferritin, TSAT, and serum iron were increased in patients with chronic kidney disease complicated by iron deficiency anemia, and these changes were statistically significant at week 16 and continued to week 52. In terms of safety, patients tolerated well during treatment.
bibliography
1. Pergola PE, Kopyt NP. Oral Ferric Maltol for the Treatment of Iron-Deficiency Anemia in Patients With CKD: A Randomized Trial and Open-Label Extension. Am J Kidney Dis. 2021 May 21:S0272-6386(21)00624-7.
2. FDA OKs Oral Ferric Maltol (Accrufer ) for Iron Deficiency in Adults - Medscape - Aug 07, 2019.