Table 1.
Characteristics of included randomized, controlled trials
| Study, First Author, Year of Publication, Year of Study, Study Name/Data Source | Inclusion criteria: Modality, TSAT, Ferritin, HGB, Iron, ESA, Other | n: All, Active, Comparator | Iron Strategy, Active versus Comparator | Iron Targets | ESA Strategy | HGB Targets | Duration | 1° Outcome | 2° Outcomes |
|---|---|---|---|---|---|---|---|---|---|
| Fishbane et al. (28), (1995), N/A, N/A | HD≥3 mo | 75 | ID 100 mg iv 2× weekly during regular HD | N/A | EPO to achieve HCT target with 2000 U increase/decrease if below/above target | HCT 30%–34% | 4 mo | N/A | N/A |
| >15% | 25 | versus | |||||||
| >100 | 50 | Oral iron (FS 325 mg po three times per day or iron polysaccharide 150 mg po two times per day) with rescue 1 g ID over ten HD if ferritin <50 ng/ml, TSAT<12.5% | |||||||
| N/A | |||||||||
| Oral≥3 mo, no iv ID for at least 6 mo | |||||||||
| EPO≥3 mo | |||||||||
| No recent bleeding, transfusions, hematologic | |||||||||
| Fudin et al. (29), (1998), N/A, N/A | Incident HD | 48 | iv ferric gluconate 62.5 mg qHD | N/A | N/A | N/A | 12, 26 mo | RBC transfusions | ferritin |
| TSAT<21% | 24 | versus | |||||||
| N/A | 12 | Oral ferrous sulfate 160 mg po daily | |||||||
| <78 | 12 | versus | |||||||
| N/A | None | ||||||||
| N/A | |||||||||
| Depleted sternal bone marrow iron stores | |||||||||
| Besarab et al. (30), (2000), N/A, N/A | HD | 42 | ID 4–6 100 mg doses during consecutive HD to increase TSAT>30% and 25–150 mg/wk to maintain TSAT 30%–50% | TSAT 20%–30% during 16–20 wk run-in phase, then | EPO to achieve HGB target | Steady state if maximal HGB variation <1.2 g/dl and EPO<500 U per dose during last 6 wk of run-in phase, 9.5–12 g/dl targeting baseline value, algorithm | 6 mo | ESA dose by power calculations | N/A |
| TSAT 19%–30%, ferritin 150–600 HGB≥9.5 g/L with MCV>80 fl | 23 | versus | 30%–50% active versus | ||||||
| N/A | 19 | ID 25–150 mg/wk to maintain TSAT 20%–30% | 20%–30% comparator | ||||||
| Stable EPO dose over previous 3 mo (±25%) >700 U 3× per 1 wk | |||||||||
| N/A | |||||||||
| Singh et al. (31), (2006), N/A, N/A | Incident or prevalent PD | 126 | IS 1000 mg iv over 28-d period as 300 mg day 1 and day 15, 400 mg day 28 | N/A | ESA at same dose before randomization, unchanged throughout study period | N/A | 8 wk with withdrawal if modality change, intervention for anemia management | Change from baseline to highest HGB | HGB response; iron stores; BP; adverse events before, during, after infusion; SAE indicates fatal or life-threatening disability or incapacity; hazard; anemia intervention management (RBC transfusion, increase in ESA, iron administration not in study protocol) |
| TSAT≤25% | 80 | versus | |||||||
| Ferritin≤500 | 46 | No iron | |||||||
| HGB≥9.5 and ≤11.5 | |||||||||
| No iv or po iron for 4 wk | |||||||||
| ESA (DPO or EPO) without dose change for 8 wk | |||||||||
| N/A | |||||||||
| Coyne et al. (32), (2007), 2004–2006, DRIVE, N/A | HD≥90 d | 134 | FG 125 mg iv ×8=1 g | N/A | EPO dose was raised by 25% and maintained for the entire study | N/A | Baseline ≤1 wk, 6 wk | Change from baseline to week 6 in HGB | Percentage of responders (HGB increase of ≥2 g/dl during the study) and time to response, change in baseline of CHr, TSAT, ferritin, CRP |
| TSAT≤25%, | 68 | versus | |||||||
| Ferritin 500–1200 | 66 | None | |||||||
| HGB≤11.0 g/dl | |||||||||
| ≤125 mg/wk iv iron previous 4 wk | |||||||||
| Stable dosage of EPO≥225 IU/kg per week or ≥22500 IU/wk for ≥2 wk | |||||||||
| N/A | |||||||||
| Provenzano et al. (33), (2009), N/A, N/A | HD≥90 d, TSAT≤30% ferritin≤600 | 230 | FX 510 mg iv ×2 during sequential HD within 5±3 d | N/A | ESA dose was required to remain constant throughout the study | N/A | 35 d but nonrandomized readmission phase | Change in HGB from baseline to 35 d | Proportion of patients achieving a ≥1-g/dl increase in HGB at day 35; change in HGB at day 21; change in TSAT, ferritin, SI, TIBC, CHr at days 21 and 35; safety analysis |
| HGB≤11.5 | 114 | versus | |||||||
| N/A | 116 | Ferrous fumarate 50 mg for 200 mg elemental iron daily ×21 d | |||||||
| Stable ±25% ESA dose for 10 d | |||||||||
| N/A | |||||||||
| Lewis et al. (34), (2015), 2010–2012, N/A | 3× Weekly HD or PD for ≥3 mo | active control trial | FC 1 g (210 mg ferric iron) tablets with protocol titration schedule (have iv iron dose 55 mg/mo) | At the discretion of the site | At the discretion of the treating physician | N/A | 2 wk Washout, 52 wk active control, 4 wk placebo control | Change in phosphate at 4 wk placebo control period | Changes over 52 wk in ferritin, TSAT, cumulative doses of iv iron, ESA |
| TSAT<50% | 441 | versus | |||||||
| Ferritin<1000 | 292 | Calcium acetate 667 mg capsules, sevalamer 800 mg tablets titrated by FDA-approved package inserts | |||||||
| N/A | 149 | and iv iron prohibited if ferritin >1000 ng/ml or TSAT>30% (have iron dose 115 mg/mo) | |||||||
| N/A | Placebo control trial | ||||||||
| N/A | 192 | ||||||||
| 3–18 Doses phosphate binders, phosphate≥2.5 and ≤8.0 mg/dl | 96 | ||||||||
| 96 |
TSAT, transferring saturation; HGB, hemoglobin; ESA, erythropoietin-stimulating agent; N/A, not reported; HD, hemodialysis; iv, intravenous; ID, iron dextran; EPO, erythropoietin; FS, ferrous sulfate; po, per ora; HCT, hematocrit; qHD, with each hemodialysis; RBC, red blood cell; MCV, mean corpuscular volume; DPO, darbopoetin; IS, iron sucrose; SAE, serious adverse event; DRIVE, dialysis patients' response to IV iron with elevated ferritin study; FG, ferric gluconate; CHr, reticulocyte hemoglobin content; CRP, C-reactive protein; FX, ferumoxytol; SI, serum iron; TIBC, total iron binding capacity; PD, peritoneal dialysis; FC, ferric citrate; FDA, Food and Drug Agency.