Background and Rationale Peripheral arterial disease (PAD) frequently coexists with chronic kidney disease (CKD). Endovascular revascularisation, a common procedure for PAD, typically relies on iodine-based contrast medium, which is nephrotoxic and a known contributor to acute kidney injury (AKI). Patients developing AKI post-revascularisation face increased long-term major cardiovascular events, progression of CKD, and mortality. Using carbon dioxide (CO2) as an alternative contrast medium may mitigate this risk, as CO2 is not nephrotoxic. Automated intra-arterial CO2 injectors have recently been developed to address previous technical constraints associated with CO2 delivery, such as procedural pain and suboptimal imaging.
Trial Design and Methodology This research is a multicentre, prospective, open-label, parallel-group randomised controlled trial. The trial takes place across at least six UK NHS hospitals providing specialist care for PAD. Following informed consent, participants are randomised via a centralised web-based system in a 1:1 ratio within 15 days of consent. Randomisation is minimised by baseline CKD stage, age, presence of tissue loss, and diabetes. The study intends to recruit 174 participants to achieve 90% power to detect a clinically meaningful difference in serum creatinine values, accounting for a 10% participant drop-out rate.
Procedural Details All pre- and post-procedure care remains identical for both the intervention and control groups, adhering to existing NHS PAD care pathways and National Institute of Health and Care Excellence (NICE) guidance, which includes standard oral and intravenous fluid therapy. The investigators will monitor renal function by recording serum creatinine levels at baseline and at 2, 30, and 90 days post-procedure. Follow-up assessments will take place either in-person at the vascular clinic or via telephone until day 90.
Qualitative and Health Economic Evaluations The trial incorporates a health economic evaluation to assess the cost-effectiveness of the automated CO2 injector from an NHS and societal perspective. This evaluation utilises intraprocedural data, healthcare resource usage data, and Quality of Life (QoL) assessments collected via validated questionnaires at 90 days post-procedure.
Additionally, a qualitative and implementation sub-study will be conducted to explore acceptability and implementation factors. A purposively selected subgroup of up to 12 participants receiving the CO2 automated injector, alongside up to 20 involved healthcare practitioners, will complete semi-structured interviews guided by the Theoretical Framework of Acceptability (TFA). Bespoke questionnaires will also be administered to practitioners to evaluate the feasibility, appropriateness, and innovation-specific implementation intentions associated with the technology.
