Table 4.
Clinical trials of iron chelators for prevention of renal and extrarenal acute organ injury
| Reference | Setting | N | Trial Design | Iron Chelation Regimen | Findings | ||
|---|---|---|---|---|---|---|---|
| Random | Placebo-Controlled | Blinded | |||||
| Menasché et al.58 | CPB | 24 | Y | Y | N | DFO 30 mg/kg IV infusion beginning 30 min before CPB onset and ending 30 min after CPB termination; additionally, DFO 250 mg/L with cardioplegic solution | DFO- versus placebo-treated patients had no difference in postoperative SCr levels, but had lower generation of superoxide radicals |
| Menasché et al.59 | CPB | 20 | Y | Y | N | DFO 30 mg/kg IV infusion beginning 30 min before CPB onset and ending 4 h after CPB onset; additionally, DFO 250 mg/L was administered via the cardioplegic solution | DFO- versus placebo-treated patients had an attenuated rise in the plasma concentration of TBARS postoperatively |
| Paraskevaidis et al.60 | CPB | 45 | Y | Y | Y | DFO 4 g IV infusion for 8 h beginning immediately after induction of anesthesia | DFO- versus placebo-treated patients had similar postoperative BUN and SCr levels, but had an attenuated rise in plasma concentration of TBARS postoperatively, and a higher postoperative LVEF |
| Chan et al.61 | STEMI | 60 | Y | Y | Y | DFO 500 mg IV bolus immediately before PCI, followed by DFO 50 mg/kg IV infusion for 12 h | DFO- versus placebo-treated patients had lower serum iron and plasma F2-isoprostane levels immediately after PCI, but no difference in CMRI-determined infarct size |
| Fraga et al.62 | Critically ill adults with prolonged hypotension | 30 | Y | Y | Y | DFO 1000 mg IV at 3.75 ml/kg per h plus NAC 250 mg/kg IV versus placebo administered within the first 48 h of documented hypotension | Patients treated with DFO plus NAC had lower circulating markers of oxidative stress and lower SCr on hospital discharge compared with placebo-treated patients |
| Fraga et al.63 | Critically ill adults with prolonged hypotensiona | 80 | Y | Y | Y | DFO 1000 mg IV at 3.75 ml/kg per h plus NAC 250 mg/kg IV versus placebo administered within the first 48 h of documented hypotension | Patients treated with DFO NAC- versus placebo-treated patients had a similar incidence of AKI (primary end point), but had lower SCr at hospital discharge (prespecified secondary end point) |
| Selim et al.65 | ICH | 294 | Y | Y | Y | DFO 32 mg/kg per d IV infusion for 3 consecutive d | DFO- versus placebo-treated patients had no difference in neurologic outcomes or adverse events |
Y, yes; N, no; IV, intravenous; SCr, serum creatinine; TBARS, thiobarbituric acid reactive substances; LVEF, left ventricular ejection fraction; STEMI, ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; CMRI, cardiac magnetic resonance imaging; ICH, intracerebral hemorrhage.
a
Prolonged hypotension was defined as new onset of hypotension for 30 consecutive min, with mean arterial pressure <60 mm Hg and not improving with fluid infusion, or need for vasopressors.