A Trial of the Arctx Cool Catheter in Acute Pancreatitis

CHILL-AP is a prospective, multicenter, randomized controlled trial evaluating the safety and effectiveness of the Arctx Cool Catheter (ACC) Set in patients hospitalized with acute pancreatitis (AP). The study is designed to support a marketing submission to the U.S. Food and Drug Administration (FDA).

Background and rationale: There are currently no FDA-approved therapies for AP; care is supportive and consists of fluid replacement, nutrition support, and pain control. In AP, the body's inflammatory response can become severe and progress to systemic inflammatory response syndrome (SIRS) and organ failure. Laboratory and early clinical evidence suggests that cooling the pancreas can calm this early inflammation, regardless of what caused the AP. The ACC Set is intended to cool the pancreas locally, without cooling the whole body, in order to reduce the severity of AP and shorten the time it takes to recover.

Investigational device: The ACC Set is made up of the Arctx Catheter and an Arctx Extension Line that connects the catheter to a Blanketrol III Hyper-Hypothermia System. The Arctx Catheter is a single-use, non-implantable tube with several channels, placed in the stomach/duodenum. Two channels circulate the cooling fluid through the connected heat exchanger; a third channel allows fluids to be given or drained through the gut.

Design and randomization: Eligible participants are randomized 1:1, stratified by site, to receive either the ACC Set plus standard of care or standard of care alone. The study may enroll up to 200 participants (approximately 100 per arm) at up to 25 sites in the United States and 1 in Latin America, with at least 50% of participants enrolled at U.S. sites and no single site enrolling more than 20% of total enrollment. Bias is minimized through randomization, objective eligibility criteria, uniform effectiveness criteria, an independent blinded image reviewer, and oversight by an independent Data Monitoring Committee (DMC).

Intervention: For participants randomized to the device arm, ACC placement and the start of cooling must occur within a total of 48 hours of symptom onset. Eligibility is reconfirmed immediately before placement. The device may remain in place for up to 72 hours, with earlier removal at the investigator's discretion; if a device is removed and replaced, the total time in use may not exceed 72 hours. An x-ray taken after placement confirms the position. Body temperature and gut (catheter) temperature are monitored during cooling. The gut is examined with an endoscope when there is a clinical reason to do so.

Standard of care and nutrition: Initial management in both arms follows American Gastroenterological Association Institute guidance, with medications given per each institution's standard of care. To support consistent assessment of the primary endpoint, feeding and the measurement of food tolerance are standardized across sites and across both arms. Standardized oral nutrition of at least 500 calories is offered, and the percentage of calories eaten, abdominal pain, and any vomiting are recorded around each feeding.

Assessments and follow-up: After randomization, nutrition intake is assessed about every 6 hours with standard mealtimes, and blood tests (CBC, CMP including amylase and lipase, and C-reactive protein) along with PASS and mPASS scoring are obtained about every 12 hours, each continuing until the participant can tolerate oral food without organ failure or SIRS. A contrast-enhanced CT is obtained at baseline and at Day 14.

Follow-up visits occur at Day 7, Day 14, and Day 30, with the Day 30 visit occurring 30 days after hospital discharge. An independent radiologist experienced in AP reviews the baseline and Day 14 contrast-enhanced CTs.

Statistical considerations: The primary effectiveness analysis is performed on the intent-to-treat (ITT) population, with sensitivity analyses on the modified ITT and per-protocol populations; safety is analyzed on all treated participants. The effectiveness sample size of 188 participants (94 per group) provides 80% power at a one-sided alpha of 0.025 to detect the expected difference in time to oral food tolerance, assuming a 5% dropout rate; the total of 200 participants also meets the goal of about 100 participants in the treatment arm for safety.

• Time to Oral Food Tolerance [Срок оценки: From randomization until oral food tolerance, assessed up to hospital discharge (expected average of 1 to 10 days).]
• Length of Hospital Stay [Срок оценки: From hospital admission to discharge (assessed up to approximately 21 days).]
• Conversion to More Severe AP Classification [Срок оценки: From randomization through the Day 30 (± 14 days) follow-up visit.]
• Time to Modified Pancreatitis Activity Scoring System (mPASS) Score ≤60 [Срок оценки: From randomization until mPASS ≤60, assessed up to hospital discharge (assessed up to approximately 21 days).]
• Time to Pancreatitis Activity Scoring System (PASS) Score ≤60 [Срок оценки: From randomization to discharge (assessed up to approximately 21 days)]
• Total Morphine Equivalent Dose (MED) [Срок оценки: From randomization until oral food tolerance without organ failure or SIRS. (Expected range 1 to 10 days)]
• Severity of Acute Pancreatitis by Modified CT Severity Index (mCTSI) at Day 14 [Срок оценки: 14 days (± 7 days) following randomization.]
• Total SIRS Duration [Срок оценки: From randomization to discharge (assessed up to approximately 21 days).]
• Change in C-Reactive Protein (CRP) [Срок оценки: From randomization until oral food tolerance without organ failure or SIRS, assessed up to hospital discharge (expected range 1 to 10 days).]
• Incidence of Organ Failure [Срок оценки: From randomization to discharge (assessed up to approximately 21 days).]
• Duration of Organ Failure [Срок оценки: From randomization to discharge (assessed up to approximately 21 days).]
• Duration of Fever [Срок оценки: From randomization to Primary Endpoint (Anticipated range 1 to 10 days)]