Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING):a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial

Background Intravenous saline is recommended in clinical practice guidelines as the cornerstone for preventing contrast-induced nephropathy in patients with compromised renal function. However, clinical-effectiveness and cost-effectiveness of this prophylactic hydration treatment in protecting renal function has not been adequately studied in the population targeted by the guidelines, against a group receiving no prophylaxis. This was the aim of the AMACING trial.Methods AMACING is a prospective, randomised, phase 3, parallel-group, open-label, non-inferiority trial of patients at risk of contrast-induced nephropathy according to current guidelines. High-risk patients (with an estimated glomerular filtration rate [eGFR] of 30-59 mL per min/1.73 m(2)) aged 18 years and older, undergoing an elective procedure requiring iodinated contrast material administration at Maastricht University Medical Centre, the Netherlands, were randomly assigned (1:1) to receive intravenous 0.9% NaCl or no prophylaxis. We excluded patients with eGFR lower than 30 mL per min/1.73 m(2), previous dialysis, or no referral for intravenous hydration. Randomisation was stratified by predefined risk factors. The primary outcome was incidence of contrast-induced nephropathy, defined as an increase in serum creatinine from baseline of more than 25% or 44 mu mol/L within 2-6 days of contrast exposure, and cost-effectiveness of no prophylaxis compared with intravenous hydration in the prevention of contrast-induced nephropathy. We measured serum creatinine immediately before, 2-6 days, and 26-35 days after contrast-material exposure. Laboratory personnel were masked to treatment allocation. Adverse events and use of resources were systematically recorded. The non-inferiority margin was set at 2.1%. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT02106234.Findings Between June 17, 2014, and July 17, 2016, 660 consecutive patients were randomly assigned to receive no prophylaxis (n = 332) or intravenous hydration (n = 328). 2-6 day serum creatinine was available for 307 (92%) of 332 patients in the no prophylaxis group and 296 (90%) of 328 patients in the intravenous hydration group. Contrast-induced nephropathy was recorded in eight (2.6%) of 307 non-hydrated patients and in eight (2.7%) of 296 hydrated patients. The absolute difference (no hydration vs hydration) was -0.10% (one-sided 95% CI -2.25 to 2.06; one-tailed p = 0.4710). No hydration was cost-saving relative to hydration. No haemodialysis or related deaths occurred within 35 days. 18 (5.5%) of 328 patients had complications associated with intravenous hydration.Interpretation We found no prophylaxis to be non-inferior and cost-saving in preventing contrast-induced nephropathy compared with intravenous hydration according to current clinical practice guidelines.