What They Did:
- Prospective, randomized, phase 3, parallel-group, open-label, non-inferiority trial
- High-risk patients (i.e.defined by an estimated glomerular filtration rate of 30 – 59 mL per min/1.73m2) who were undergoing an elective procedure requiring iodinated contrast material administration were randomly assigned to receive: IV 0.9% Normal Saline vs No IV Fluids
Hydration Protocols:
- Standard Protocol: IV 0.9% NaCL 3 – 4mL/kg per hr during 4hr before and 4hr after contrast administration
- Long Protocol: Intravenous 0.9% NaCl 1mL/kg per hr during 12hr before and 12hr after contrast administration
Outcomes:
- Primary: Incidence of Contrast-Induced Nephropathy – Defined as an increase in serum creatinine from baseline of more than 25% or 44umol/L within 2 – 6 days after contrast exposure
- Secondary:
- Mean change in serum creatinine from baseline at 2 – 6 and 26 – 35days after contrast administration
- Major Adverse Events: All-Cause Mortality, Renal Replacement Therapy, Intensive Care Admission, and Sequelae of Fluid Administration
- Major Renal Adverse Events: Renal Failure (Defined as eGFR <15mL per min/1.73m2), renal decline with >10 eGFR units, renal decline to eGFR <30mL per min/1.73m2, or a combination of the latter two, at 26 – 35 days
- Major Fluid Administration Events: Symptomatic Heart Failure, Hypernatremia or Hyponatremia, and Supraventricular or Ventricular arrhythmias
- Cost-effectiveness of no prophylaxis compared with intravenous hydration
Inclusion:
- Estimated glomerular filtration rate (eGFR) between 45 – 59mL per min/1.73m2 combined with either diabetes, OR at least two predefined risk factors (age >75years, anemia defined as hematocrit <0.39 L/L for men and <0.36 L/L for women, Cardiovascular disease, Non-steroidal anti-inflammatory drug or diuretic nephrotoxic medication
- eGFR between 30 – 45 mL per min/1.73m2
- Multiple Myeloma
- Lymphoplasmacytic Lymphoma with small chain proteinuria
Exclusion:
- Inability to Obtain Informed Consent
- eGFR < 30 mL per min/1.73m2
- Renal Replacement Therapy
- Emergency Procedures
- Intensive Care Patients
- Known Inability to Plan Primary Endpoint Data Collection
- No Referral for Prophylactic Hydration
- Participation in Another Randomized Trial
- Isolation (Infection Control)
Results:
- >650 patients randomized
Strengths:
- Prospective, Randomized Clinical Trial
- Consecutive Patients
- Blinding of laboratory staff
- Randomization stratified to Preplanned Subgroup Analyses: Diabetes (yes vs no), eGFR (<45 vs ≥45 mL per min/1.73m2), contrast administration route (Intravenous vs Intra-arterial, and procedure type (diagnostic vs interventional)
- Baseline characteristics balanced between groups
- Data for serum creatinine level at days 2 – 6 was available for 91% of the 660 patients
Limitations:
- Single Center
- Sample size reduced during the study from 1300 to 600 patients, but most likely did not affect validity of study as non-inferiority margin of 2.1% was predefined
- Open-label design because masking of intervention was almost impossible
- Post contrast serum creatinine measurements not available for all patients, but baseline characteristics of patients were similar to patients included in the study
- Due to the paucity of placebo-controlled trials on the effectiveness of prophylactic hydration, setting a non-inferiority margin for contrast-induced nephropathy was difficult (Assumed incidence of CIN would be 2.4% and chose a non-inferiority margin of 2.1%)
Discussion:
- In this trial minimum volume, pre-warmed, low-osmolar, monomer, non—ionic, contrast material lopromide, at 300mg iodine per mL. were used, not high osmolar contrast media
- Mean total IV hydration volume given in the prehydration group was 1637mL and Mean volume of contrast material administered was 91mL
Author Conclusion: “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.”
Clinical Take Home Point: This is the first prospective, randomized clinical trial evaluating the effectiveness of intravenous prehydration to prevent CIN in high risk patients. With the low- and iso-osmolar contrast agents being used today, withholding prophylaxis for high risk patients with an eGFR >29 mL per min/1.73m2 may be feasible and cost saving, but this still warrants external validation prior to implementation.
References:
- Nijssen EC et al. 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. Lancet 2017; S0140 – 6736(17)30057 – 0. PMID: 28233565
For More Thoughts on This Topic Checkout:
- Richard Sinert at EMDocs: Nephropathy – Confounding Causation
- Celia Bradford at The Bottom Line: Prophylactic Hydration to Protect Renal Function from Intravascular Iodinated Contrast material in Patients at High Risk of Contrast-Induced Nephropathy
Post Peer Reviewed By: Scott Wieters (Twitter: EMedCoach)
The post The AMACING Trial: Prehydration to Prevent Contrast Induced Nephropathy (CIN)? appeared first on REBEL EM - Emergency Medicine Blog.