Acute kidney injury (AKI) is a common complication in patients suffering from acute coronary
syndromes (ACS) and treated by percutaneous coronary intervention (PCI). This complication
has been associated with higher early and late adverse events. It has been emphasized that
the pathogenesis of AKI in the setting of ACS is multifactorial, including age, unstable
hemodynamic conditions, co-morbidities (that is, diabetes mellitus and anemia) pre-existing
chronic kidney disease, dehydration and administration of nephrotoxic drugs. However, the
role of iodinated contrast media (CM) has been well established. Hydration represents the
cornerstone in contrast-induced AKI (CI-AKI) prevention. However, at present there is no
consensus on how hydration should be carried out, especially in ACS patients, and all the the
recommended hydration regimens have limited applicability in the urgent/emergent settings
such as ACS. Several targeted hydration regimens have been proposed, but none has been tested
in ACS patients; in the present trial the investigators will adopt the left ventricular end
diastolic pressure (LVEDP) -guided hydration because this approach is simple and easy to
implement in the current target population. The CM volume used is an independent predictor of
CI-AKI and the concept that "the lower the CM volume, the lower the CI-AKI risk" is generally
accepted. The administration of a CM volume >3X glomerular filtration rate (GFR) is
suggestive of increased risk of CI-AKI. To date the use of manual injections with a manifold
remains the preferred technique in the majority of catheterization laboratories. In
particular, manual injection is often favored for interventional procedures, which require
low, variable-flow pressure injections. The AVERT trial demonstrated that CM volume is
significantly lower in patients randomized to DyeVert™ in comparison to control (36.9 ± 10.9
mL versus 62.5 ± 12.7 mL, p < 0.001) and the observed reduction in CM volume used was most
evident in patients undergoing PCI. Therefore, in this scenario is of outmost importance to
limit the CM volume in the attempt to prevent CI-AKI. The aim of the REnal Insufficiency
Following Contrast MEDIA Administration TriaL IV (REMEDIAL IV) is to test whether the use of
the DyeVert system is effective in reducing CI-AKI rate in ACS patients undergoing urgent or
immediate (within 2 hours) invasive diagnostic and/or interventional cardiovascular
procedures.
METHODS All patients with ACS scheduled for urgent/immediate coronary angiography/angioplasty
will be screened for inclusion/exclusion criteria. Diagnosis of ACS (both ST-Elevation
Myocardial Infarction [STEMI] and high-risk Non-ST-Elevation Myocardial Infarction
[Non-STEMI]) will be established in accordance with guidelines, including a typical chest
pain history, diagnostic electrocardiographic changes, and serial increase of cardiac
biomarkers. All patients with inclusion/exclusion criteria satisfied and who will agree to
sign the informed consent will be enrolled into the trial. The REMEDIAL IV trial will be
conducted at a pool of Italian interventional cardiology centers, according to the principles
of the Declaration of Helsinki and Good Clinical Practice and has been approved by the local
Ethic Committees.
All the patients included into the study will receive intravenous 0.9% sodium chloride as
soon as in the catheterization laboratory; the hydration regimen will be defined according to
the hemodynamic conditions, as defined below. The patients will be then randomized into 2
groups: 1) DyeVert group, and 2) Control group.
STUDY ENDPOINTS The primary endpoint of the trial is the rate of CI-AKI. CI-AKI is defined as
an increase in the serum creatinine (sCr) concentration ≥ 0.3 mg/dL from the baseline value
within 5 days after CM administration or the need for dialysis. Secondary end-points will
include: 1) differences in the CM volume in the 2 groups; 2) an increase in the sCr
concentration ≥25% within 5 days after CM exposure; 4) the severity of AKI assessed according
to the Acute Kidney Injury Network criteria: Stage 1, a sCr increase ≥0.3 mg/dL or ≥1.5-1.9
times from baseline; Stage 2, a sCr increase ≥2.0-2.9 times from baseline; and Stage 3, a sCr
increase ≥3.0 times from baseline or the need for dialysis; 5) changes in the serum cystatin
C concentration at 24 and 48 hours after CM exposure; 6) the rate of acute renal failure
requiring dialysis (defined as a decrease in renal function necessitating acute hemodialysis,
ultrafiltration or peritoneal dialysis within the first 5 days post-intervention); 7) the
rate of in-hospital, 6 and 12-month major adverse events (MAE), including death, renal
failure requiring dialysis, acute pulmonary edema, and sustained kidney injury. Sustained
kidney injury is defined as a persistent ≥25% GFR reduction compared to baseline at 6 and 12
months; and 8) the length in in-hospital stay, calculated as the sum of the number of days
since admission until discharge from the hospital.
