A contrast sparing strategy using automated Carbon Dioxide Injection during PERIpheral vascular interventions for PREVENTion of Major Adverse Kidney Events (MAKE): the PeriPREVENT randomized controlled trial

• Applicant: Professorin Dr. Sabine Steiner
• Subject Area: Cardiology, Angiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 496265798

The use of iodinated contrast media (CM) has become indispensable in modern medicine for a wide range of applications and procedures including coronary and peripheral vascular interventions. CM administration has been identified as a risk factor for acute kidney injury (AKI), but also other factors play a role for the observed deterioration of kidney function. While the clinical impact of CM associated AKI (CA-AKI) is intensely discussed by experts, CA-AKI has also been associated with serious long-term adverse events including an increased death rate. To date, no randomized trial has examined the risk of CM administration on both CA-AKI and subsequent clinical events. Clinical research is particularly sparse in patients with peripheral arterial disease despite their poor prognosis. Thus, there are also few data on the incidence and clinical outcomes of CA-AKI after peripheral vascular interventions (PVI). This particularly raises concerns as PVIs are increasingly performed as an alternative to open bypass surgery. For PVI, there is an alternative to CM administration. Carbon dioxide (CO2), acting as a negative contrast agent, has been used for a variety of vascular procedures because of its high solubility rate and rapid diffusibility via the lungs. CO2 is safe for peripheral intravascular use, but should not be used above the diaphragm to avoid the possibility of causing a cerebral air embolism. The development of automated CO2 injection systems has improved image quality and tolerability with less non-renal side effects (e.g. nausea) allowing a more widespread use in clinical routine. To date, research on the clinical benefit of CO2 angiography is limited and based predominantly on observational data. Although these data are promising, further high quality research is needed to demonstrate safety and efficacy in a broader range of patients. In the absence of a clear understanding of the importance of CA-AKI and a proven reno-protective strategy, we propose a randomized controlled trial to compare the safety and incidence of CA-AKI and serious adverse renal events using a maximal contrast sparing strategy with CO2 versus a standard strategy with CM for peripheral angiography in patients at increased risk for CA-AKI. The trial addresses an area of high clinical uncertainty and equipoise where sound scientific evidence is urgently needed and its results can be directly translated into routine clinical practice by clarifying the potential benefits and risks of an alternative treatment strategy with CO2 angiography. Beyond addressing post-procedural CA-AKI, the study will be sufficiently powered to investigate the effects of CM sparing on clinically relevant endpoints at 90 days in order to elucidate the relationship between CA-AKI and subsequent major adverse kidney events.

• DFG Programme: Clinical Trials