Table 2.

Summary of the clinical trials of iron supplementation in patients with CKD

ReferenceTitleYearPopulationnFollow-upInterventionOutcomesSafetyAdditional
Coyne, et al.55DRIVE I2007Patients undergoing hemodialysis with Hgb ≤11 g/dl, ferritin 500–1200 ng/ml, TSAT ≤25%, and epoetin dosage ≥225 IU/kg per wk or ≥22,500 IU/wk1346 wkNo iron (control) versus 125 mg IV ferric gluconatePatients receiving ferric gluconate had higher Hgb (P=0.028), more rapid Hgb response (P=0.035) No difference in adverse eventsFerritin levels ranged 500–1200 and had no correlation with outcomes
Kapoian, et al.56DRIVE II2008Same as DRIVE I11212 wk (6 wk from DRIVE I)No iron (control) versus 125 mg IV ferric gluconate for the first 6 wk. For the additional 6 wk, treatment was per centerFerric gluconate group had significantly lower EPO doses; 84% of the treatment arm maintained Hgb >11.0 versus 68% of the control (P<0.05)More adverse events in control group (IRR 1.73, P=0.041)
MacDougall, et al.57PIVOTAL2019Patients undergoing hemodialysis2141Median=2.1 yrIron sucrose: high dose (400 mg) given monthly versus low dose (0–400 mg) given reactively each mo based on ferritin <200 mcg/L or TSAT <20%Composite outcome (nonfatal myocardial infarction, stroke, heart failure hospitalization, any-cause death) was 29% versus 32% (P=0.04) in the high-dose versus low-dose group; less ESA use in the high-dose groupSimilar rates of infection and overall adverse events; vascular access thrombosis rates were 24% in the high-dose versus 21% in the low-dose group (P=0.12); but lower rates of fatal or nonfatal myocardial infarction were noted in the high-dose group (estimated treatment effect 0.69 [95% CI: 0.52-0.93])Rates of stroke were similar for both groups but lower rates of fatal or nonfatal myocardial infarction were noted in the high-dose group
Agarwal, et al.58REVOKE2015Patients with stage 3 or 4 CKD and IDA1362 yrOpen-label ferrous sulfate 325 mg TID for 8 wk versus IV iron sucrose 200 mg every 2 wk (total dose 1 g)Similar decline in eGFR; similar improvement in Hgb; similar ESA doseInfections: IRR 2.12 for IV versus oral iron groups (P<0.006). CV events: IRR 2.51 for IV versus oral iron groups (P<0.001)Not powered for safety
Macdougall, et al.59FIND-CKD2017Patients with nondialysis-dependent CKD and IDA without ESA use3531 yrOral iron (ferrous sulfate 304 mg twice daily) versus FCM at high dose (500 or 1000 mg monthly based on ferritin) versus FCM at low dose (2 mmg monthly based on ferritin)Time to initiation of additional anemia therapy: the primary end point occurred in 23%, 32%, 32% in the high-ferritin FCM, low-ferritin FCM and oral iron groups, respectively (HR, 0.65; 95% CI, 0.44 to 0.95; P=0.026 for high-ferritin FCM versus oral iron)No significant difference in adverse renal outcomesFerritin levels were significantly higher in the high-dose FCM group
Charytan, et al.602013Adult Patients with history of NDD-CKD of at least 3 mo or HD-CKD of at least 6 mo with IDA and no recent iron use416 NDD-CKD, 97 HD-CKD30 dStandard medical care (provider determined: no iron, oral iron, or IV iron) versus FCM (15 mg/kg in NDD-CKD or 200 mg in HD-CKD)Safety of high-dose FCM: no difference in safety events between groups; no difference in the proportion of patients with an increase of 1 g/dl in Hgb or Hgb >12 g/dlPrimary end point: high incidence of serious events in the standard care group (notably iron sucrose or ferrous gluconate), p<0.01Not powered for secondary end points
Onken, et al.61REPAIR-IDA2014Patients with CKD and IDA with stable ESA dose (if applicable)258456 dFCM (15 mg/kg×2 doses) versus IV iron sucrose (200 mg×5 doses)Composite safety outcome (all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, CHF, arrythmia, hypertension, hypotension): no significant difference; mean change in Hgb from baseline was higher in the FCM groupComposite (all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, CHF, arrythmia, hypertension, hypotension): no major difference; significant difference in number of transient hypertension in FCM group and hypotension in iron sucrose groupFCM noninferior for increases in TSAT, ferritin
  • IRR, incident risk ratio; TID, three times a day; NDD-CKD, non-dialysis dependent chronic kidney disease; HD-CKD, hemodialysis-dependent CKD; CHF, congestive heart failure.