Comparison of Intravenous Iohexol-Enhanced CT Versus Non-Contrast CT in Acute Abdomen Patients with Impaired Renal Function: A Multicenter Randomized Trial

The primary objective of the study is to evaluate the **superiority** of the diagnostic strategy using intravenous (IV) contrast computed tomography (CT) compared to native CT in patients presenting with acute abdomen and impaired renal function. This is clinically relevant as it aims to determine the most effective imaging modality for accurate diagnosis in this patient population, potentially impacting treatment decisions and outcomes. The study focuses on patients requiring emergency abdominal or body CT with an estimated glomerular filtration rate (eGFR) of 15-45 ml/min/1.73 m², calculated from the last available plasma creatinine value taken within 24 hours before randomization.

The clinical trial involves a study population comprising both **male** and **female** participants, categorized within age ranges 3 and 4, which typically correspond to adults and older adults. The participants are individuals requiring emergency abdominal or body CT scans, with an estimated glomerular filtration rate (**eGFR**) between 15-45 ml/min/1.73 m², indicating impaired renal function. This eGFR is calculated from the most recent plasma creatinine value obtained within 24 hours prior to randomization. The trial includes a vulnerable population, reflecting the critical nature of the medical condition under investigation. The sponsor has not provided information regarding the total number of participants. Selection criteria focus on the necessity for emergency imaging and specific renal function parameters, without additional lifestyle considerations being specified.

The clinical trial is designed as a **randomized controlled trial** to evaluate the diagnostic strategy of using intravenous (IV) contrast computed tomography (CT) versus native CT in patients with acute abdomen and impaired renal function. The trial is open-label and multicenter, with the primary objective of assessing the superiority of the IV contrast CT approach. The study will involve patients requiring emergency abdominal or body CT with an estimated glomerular filtration rate (eGFR) of 15-45 ml/min/1.73 m², calculated from the last available plasma creatinine value taken within 24 hours before randomization. The trial is expected to commence recruitment on March 12, 2025, and conclude by December 31, 2042.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the principal inclusion criteria. The primary endpoint is a composite outcome of all-cause mortality or renal replacement therapy within 90 days of contrast medium exposure. Secondary endpoints include the most severe acute kidney injury (AKI) grade defined by KDIGO classification on plasma creatinine within 72 hours after CT, any organ dysfunction defined by at least 2 mSOFA points excluding the central nervous system 48 hours after CT, alive and hospital-free days within 90 days after CT, and time from imaging to definitive treatment during the hospital stay.

The expected length of participant involvement is up to 90 days post-CT, with follow-up visits scheduled to monitor outcomes and collect data on the endpoints. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial will utilize **iohexol** as the active substance in the IV contrast medium, administered as a solution for injection via IV injection or infusion. The study is categorized as low intervention, as CT contrast media are routinely used in clinical practice.

The clinical trial involves the use of **Omnipaque 350 mg I/ml** solution for injection, which contains the active substance **iohexol**. This pharmaceutical form is a solution intended for intravenous administration, either by injection or infusion. The maximum daily dose and total dose are both set at 1 unit, with a maximum treatment period of 1 day. The administration of Omnipaque is conducted under controlled conditions to ensure participant safety and adherence to the study protocol. The product is manufactured by GE Healthcare BV and is not a pediatric formulation. The chemical origin of iohexol is confirmed, and it is classified under the ATC code V08AB02.

In this trial, the experimental medication is compared against a standard-of-care therapy, which involves the use of native computed tomography (CT) without contrast. This comparator treatment serves as a control to evaluate the diagnostic superiority of the intravenous contrast-enhanced CT in patients with acute abdomen and impaired renal function. The study is designed to monitor participant compliance with the dosing schedule and administration route, ensuring that all procedures align with the trial's objectives and regulatory requirements.

Efficacy in the clinical trial titled "INtravenous Contrast computed tomography versus native computed tomography in patients with acute Abdomen and impaired Renal functiOn (INCARO)" will be assessed using a combination of primary and secondary endpoints. The primary endpoint is a composite outcome that includes all-cause mortality or the need for renal replacement therapy within 90 days following exposure to the contrast medium. This endpoint will provide a comprehensive measure of the trial's main objective, which is to evaluate the superiority of intravenous contrast CT over native CT in patients with impaired renal function.

Secondary endpoints will further assess efficacy by evaluating the most severe acute kidney injury (AKI) grade as defined by the KDIGO classification based on plasma creatinine levels within 72 hours post-CT. Additionally, any organ dysfunction will be measured by at least 2 mSOFA points, excluding the central nervous system, within 48 hours after CT. Other secondary measures include the number of alive and hospital-free days within 90 days post-CT and the time from imaging to definitive treatment during the hospital stay. These endpoints will be measured at specified time points to ensure a thorough evaluation of the treatment's impact on patient outcomes.