Efficacy and safety of polysaccharide iron complex capsules compared with iron sucrose in hemodialysis patients: study protocol for a randomized, open-label, positive control, multicenter trial (IHOPE)

Abstract

Background: Anemia is one of the main complications of chronic kidney disease especially kidney failure, which includes treatment with erythropoiesis-stimulating agents and iron supplementation, including intravenous and oral iron. However, intravenous iron may pose limitations, such as potential infusion reactions. Oral iron is mainly composed of divalent iron, which can excessively stimulate the gastrointestinal tract. Iron polysaccharide complex capsules are a novel oral iron trivalent supplement with higher iron content and lower gastrointestinal irritation. However, since high-quality evidence-based medicinal support is lacking, it is necessary to conduct clinical studies to further evaluate the effectiveness and safety of oral iron polysaccharide complex in chronic kidney disease patients.

Methods: This randomized controlled trial uses an open-label, parallel group design, where the efficacy and safety of maintenance hemodialysis (MHD) participants is evaluated. The experimental group is assigned erythropoietins and iron polysaccharide complex (two capsules each time, bid), and the control group is assigned erythropoietin and sucrose iron (100mg, 2w) injection. Participants (aged 18-75 years) undergoing maintenance hemodialysis were considered for screening. Inclusion criteria included hemoglobin (Hb) ≥110g/L and < 130g/L, transferrin saturation (TSAT) > 20% and < 50%, and serum ferritin (SF) > 200μg/L and < 500μg/L. Exclusion criteria included acute or chronic bleeding, serum albumin < 35g/L, hypersensitive C-reactive protein (HsCRP) > 10 mg/L, and severe secondary hyperparathyroidism (iPTH ≥ 800 pg/mL). Full inclusion and exclusion criteria are described in the "Methods" section. The primary endpoint is TSAT of the participants at week 12. Secondary endpoints include Hb, SF, hematocrit (Hct), HsCRP, pharmacoeconomic evaluation, drug costs, quality of life, and indicators of oxidative stress. The treatment will last for 24 weeks with a follow-up visit at baseline (within 7 days prior to initial treatment) and weeks 4, 8, 12, 16, 20, and 24 after initial treatment. This clinical research includes 9 hemodialysis centers in mainland China and plans to enroll 186 participants.

Discussion: It is expected that it will provide strong evidence to reveal the clinical efficacy and safety of oral iron in the treatment of chronic CKD-related anemia in MHD patients through this clinical trial.

Trial registration: Chinese Clinical Trial Registry ChiCTR2000031166 . Registered on March 23, 2020.

Keywords: Anemia; Efficacy and safety; Hemodialysis; Kidney failure; Multicenter; Oral iron.

Fig. 1

Flowchart of the test scheme. Experimental group [conventional drug (erythropoietin) therapy+ iron polysaccharide complex], control group [conventional drug (erythropoietin) therapy + iron sucrose injection]. Primary outcome: TSAT 12 weeks after treatment. Secondary outcomes: iron metabolism, oxidative stress, safety evaluation, pharmacoeconomic evaluation, quality of life score, etc.

Fig. 2

Schedule of enrollment, interventions, and assessments. ICF, informed consent form; ECG, electrocardiogram; TSAT, transferrin saturation; SF, serum ferritin; HsCRP, hypersensitive C-reactive protein; Hct, hematocrit; Hb, hemoglobin