Strategic Timing of Endoscopic Interventions in Infected Necrotizing Pancreatitis (STEP-IN)

Orlando Health, Inc.

Status: Enrolling

Conditions: Pancreatitis, Acute Necrotizing

Treatments: Procedure: EUS-guided transluminal drainage of necrotic collection

Study type: Interventional

Funder types: Other

Identifiers

NCT07406698

2401309

Details and patient eligibility

About

Pancreatic necrosis complicates approximately 20-30% of severe acute pancreatitis cases. While many collections resolve without intervention, persistent symptomatic collections-particularly when infected-are associated with significant morbidity and mortality and frequently require procedural management. Current guidelines recommend delaying intervention until collections are fully walled off, typically around four weeks. However, in clinical practice, many patients deteriorate before this window is reached.

Prospective data from our institution, supported by recent meta-analyses, suggest that early intervention using modern endoscopic techniques can be performed safely, even when undertaken within the first four weeks of disease onset. We believe that, in appropriately selected patients, early endoscopic intervention may prevent clinical deterioration, reduce complications, shorten hospital stay, and decrease overall healthcare utilization compared with a delayed approach.

To formally evaluate this strategy, an international, multicenter randomized trial is being conducted, entitled Strategic Timing of Endoscopic Procedural Interventions in Infected Necrotizing Pancreatitis (STEP-IN Trial).

Full description

Acute pancreatitis imposes a significant burden on the US health-care system, resulting in approximately 300,000 hospital admissions annually and generating costs exceeding $2 billion. Necrotizing pancreatitis develops in approximately 20 to 30% of patients with acute pancreatitis. It can mature into a contained necrotic collection, typically four weeks into the disease course. While some collections may resolve without an intervention, persistent collections can result in symptoms such as pain, abdominal fullness restricting nutrition, vomiting due to gastric outlet obstruction, obstructive jaundice due to a large collection in the pancreatic head, new-onset or persisting organ failure, continued unwellness or infection that is associated with a mortality of 15-20%, and requires drainage and necrosectomy.

International guidelines recommend that, when possible, treatment should be delayed in patients with suspected or confirmed infected necrotizing pancreatitis, to allow for the collection to be walled-off with better demarcation and liquefaction of the necrosis, which generally takes around 4 weeks. The main rationale for postponement of an invasive intervention is to prevent complications, but this rationale originated from an era when open surgical necrosectomy was performed.

Recently, there has been a shift away from open surgery towards minimally invasive treatment approaches. The current standard approach for treatment is a minimally invasive step-up approach with percutaneous catheter or transluminal endoscopic drainage as the first step, followed by video-assisted retroperitoneal/sinus-tract or transgastric necrosectomy. The development of cautery-enhanced lumen-apposing metal stents (LAMS) for endoscopic drainage has significantly simplified the technical aspects of the procedure that facilitates its performance even in very sick patients.

Although international guidelines recommend postponing treatment until 4-weeks when the necrosis is better demarcated, in an international survey of expert pancreatologists, 45% of the respondents reported that they recommend immediate catheter drainage as soon as infected pancreatic and peripancreatic necrosis is diagnosed. In addition, a recent clinical practice guideline from the American Gastroenterological Association states that catheter drainage should be strongly considered when there is a concern of infection, even in the early phase of disease. However, a multicenter, randomized trial did not show superiority for immediate over postponed catheter drainage in reducing complications in patients with infected necrotizing pancreatitis.

Prospective data from our institution and from the meta-analysis suggest that interventions can be undertaken safely adopting state-of-the-art endoscopic methods even when the onset of pancreatitis is less than 4 weeks. Our data also suggest that although a significant proportion of patients undergoing early interventions (adopting an endoscopic approach) do not have a fully encapsulated collection, their treatment outcomes are not negatively impacted by such approach. If an early intervention, adopting an endoscopic approach, can be undertaken safely, it potentially can prevent further clinical deterioration and therefore complications, decrease length of hospitalization as patients may not have to wait for 3 to 4 weeks and overall treatment costs as compared to postponing the intervention until 4-weeks when the necrosis is fully walled-off.

The STEP-IN trial therefore is a natural step in the advancement of our understanding of timing of interventions in necrotizing pancreatitis as it answers an important clinical question: can early interventions be undertaken safely without subjecting patients to an arbitrary time frame of 4-weeks? In this study we challenge the existing paradigm of delayed intervention in attempt to further improve the clinical outcomes in patients with infected necrotizing pancreatitis.

Enrollment: 104 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years

2. Patients with symptomatic necrotic collection diagnosed on MRI or CT abdomen/pelvis, defined as fluid collection in the setting of documented pancreatic necrosis that contains necrotic material and encased within a partial or complete wall.

3. Documented or suspected infected necrotizing pancreatitis 1) Documented infected necrotizing pancreatitis, defined as: i. Positive culture obtained with percutaneous fine needle aspiration from the pancreatic necrotic collection (if intervention is undertaken ≤14 days of onset of acute pancreatitis) ii. OR gas in the necrotic collection on imaging at any time. 2) Suspected infected necrotizing pancreatitis, if >14 days after onset of disease, defined as: i. Persistent organ failure in patients admitted to the ICU ii. OR presence of at least three of the following six clinical/laboratory parameters (SIRS criteria or elevated CRP or elevated procalcitonin) with no other infection focus. These clinical criteria are considered sufficiently reliable only after the initial 14 days of acute pancreatitis:

   1. Temperature >100.4 °F or <96.8 °F
   2. Heart rate > 90 beats/min
   3. Respiratory rate >20 breaths/min or PaCO2 < 32 mmHg
   4. WBC count >12,000/mm³, or <4,000/mm³, or more than 10% immature band cells
   5. CRP ≥ 30mg/L
   6. Procalcitonin ≥ 1ng/mL

4. Endoscopic drainage of the necrotic collection is technically feasible as deemed by the treating physician.

Exclusion criteria

1. Age < 18 years
2. > 26 days after the onset of acute pancreatitis
3. Indication for emergency laparotomy for abdominal catastrophe (e.g. bleeding, bowel perforation, abdominal compartment syndrome).
4. Necrotic collection is not amenable for endoscopic intervention.
5. Pregnancy.
6. Unable to obtain informed consent from the patient or legally authorized representative.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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104 participants in 2 patient groups

Early endoscopic intervention in infected necrotizing pancreatitis

Active Comparator group

Description:

In the early treatment group, EUS-guided drainage is undertaken within 72 hours of randomization, earlier than 28 days after the onset of acute pancreatitis.

Treatment:

Procedure: EUS-guided transluminal drainage of necrotic collection

Postponed endoscopic intervention in infected necrotizing pancreatitis

Active Comparator group

Description:

In the postponed treatment group, EUS-guided drainage is undertaken only from 28 days after the onset of acute pancreatitis when the collection is fully or predominantly walled-off (encapsulated).

Treatment:

Procedure: EUS-guided transluminal drainage of necrotic collection