Clinical trial NCT06553651: Necrosectomy With Cryotechnology for Accelerated Removal
Official title: Necrosectomy With Cryotechnology for Accelerated Removal
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pancreatic Necrosis
Acute Pancreatitis
Acute Pancreatic Necrosis
Necrosis
Necrosis Pancreas
Walled-Off Pancreatic Necrosis
Keywords: Direct Endoscopic Necrosectomy (DEN)
Endoscopic Necrosectomy
Pancreatic Necrosectomy
Necrosectomy
Cryotherapy
Cryotechnology
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Erbe Elektromedizin GmbH
First posted: 2024-08-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Pilot, single-center, open-label, prospective, single-arm clinical study
Primary purpose: TREATMENT

Brief summary: Pancreatic necrosis is a serious complication of acute pancreatitis. Pancreatic necrosis involves the irreversible death of pancreatic tissue, which can lead to severe health issues, including infections and an increased risk of death. An endoscopic procedure called direct endoscopic necrosectomy (DEN) is typically performed to remove this necrotic pancreatic tissue as a minimally invasive treatment. This procedure is performed using a thin, flexible, lighted tube called an endoscope and endoscopic instruments that are used with working channels through the scope. Current methods for removing necrotic tissue involve using endoscopic devices such as snares, baskets, nets, and forceps. However, these standard methods are often not very effective because the necrotic tissue can be sticky and hard to grasp. This DEN procedure is part of regular clinical care to treat this condition and remove necrotic tissue from the pancreas.

For this research study, the same DEN procedure will be followed with the exception of the device used for the removal of the necrotic tissue. Instead of using forceps, snares, or other traditional tools, a cryoprobe will be used. Cryoprobes work by using extremely cold temperatures to freeze and adhere to the necrotic tissue, making it easier to remove. This method might be better because it can secure larger tissue samples and potentially reduce complications associated with traditional methods. Cryotechnology is successfully used in endoscopy to remove necrotic tissue, foreign bodies and more, but has not been extensively tested in pancreatic necrosis. Cryoprobes are FDA approved medical devices with an established safety record. They are used successfully in very sensitive areas such as the lungs. This study aims to evaluate the safety and effectiveness of cryotechnology for DEN.

Detailed description: Acute pancreatitis is the most common gastrointestinal disease requiring acute hospital admission. Pancreatic necrosis, a serious complication of acute pancreatitis, is the irreversible death of pancreatic tissue and, in some cases, surrounding abdominal tissue. Worldwide, the incidence of acute pancreatitis ranges from 13 to 45 cases per 100,000 people per year, with a subset progressing to necrotizing pancreatitis. Approximately 5-10% of acute pancreatitis cases progress to this severe form, which carries a significant morbidity and mortality burden, with mortality rates escalating to as high as 32% in cases complicated by infection. The management of pancreatic necrosis is challenging and requires several therapeutic interventions to mitigate the high morbidity and mortality associated with this condition.

The treatment of pancreatic necrosis includes several therapeutic strategies, each with varying degrees of invasiveness, efficacy, and associated risks:

Surgical debridement: Traditionally, surgical debridement has been the cornerstone of treatment for pancreatic necrosis, with the goal of removing necrotic tissue. Although effective, this approach is associated with significant risks, including high morbidity and mortality rates, as high as 39% in some studies. Surgical debridement is a very invasive procedure and often not suitable for patients with severe pancreatitis and their often compromised health status.

Percutaneous Catheter Drainage (PCD): A less invasive alternative to surgery, PCD facilitates drainage of infected necrotic fluid collections. However, its effectiveness is limited by its inability to effectively remove solid necrotic debris. This limitation often requires additional interventions or procedures.

Endoscopic necrosectomy: This minimally invasive technique involves the endoscopic removal of necrotic tissue through the stomach or duodenum. Endoscopic necrosectomy, particularly when used in a step-up approach that may combine PCD with endoscopic drainage and debridement, has been shown to reduce morbidity compared to surgery. Despite the better outcome of the endoscopic technique, there is a gap in effective devices for necrotic tissue removal. Primarily, devices that are utilized include polypectomy snares, biliary baskets, food bolus nets (Roth nets), and forceps. As they are not designed for this indication, their use is often sophisticated and not always successful. As a result, fragmentation and removal as well as a complete debridement of the necrotic tissue is not always achieved, and multiple sessions are required. In a large multicenter trial in the United States, the total number of interventions ranged from 3.1 (immediate direct endoscopic necrosectomy DEN) to 3.9 (delayed DEN). This reflects a significant limitation in the current management of pancreatic necrosis and requires alternative approaches.

Cryotechnology:

In contrast to conventional methods, cryotechnology provides a method for obtaining large tissue samples by utilizing the Joule-Thompson effect for the production of extremely cold temperatures at the probe tip.This involves the internal flow of carbon dioxide (CO2) from a high pressure source to a small nozzle at the tip of the instrument where it expands. The gas expansion causes a large temperature drop (Joule-Thomson effect) and as a result, the surrounding instrument tip is cooled. The expanded gas is returned internally from the tip to the cryosurgical unit via the return tube.

This technology is widely available and used in endoscopy, particularly in the field of pulmonology. Cryoprobes are flexible endoscopic instruments that are currently available in different diameters, 1.1 mm, 1.7 mm, and 2.4 mm. The longstanding safety and efficacy profile have demonstrated results in the safe and efficient management of the following clinical applications, biopsy, extraction and devitalization. They are intended for applications such as the removal of foreign bodies, mucus plugs, blood clots, necrotic tissue, tissue tumors (palliative recanalization) and tissue biopsies. Tissue samples obtained with this technique (cryoadhesion) have been shown to be heavier and larger than those obtained with conventional forceps.

Potential for Pancreatic Necrosis and Significance:

The successful implementation of cryotechnology for extraction suggests its potential applicability for pancreatic necrosectomy. The use of cryoprobes for minimally invasive endoscopic removal of necrotic pancreatic tissue may represent a novel approach that overcomes the limitations of existing strategies. The ability of cryotechnology to secure larger tissue samples without significant bleeding risks, coupled with its safety profile, provides an opportunity to improve the management of necrotizing pancreatitis. This study aims to investigate the safety, efficacy, and feasibility of cryoprobe use for the endoscopic removal of necrotic tissue, setting the stage for future clinical advances in the management of necrotizing pancreatitis.

Eligibility criteria: Inclusion Criteria:

* Subjects aged 18 years and above, inclusive of both males and females.
* Patients with symptomatic pancreatic necrosis resulting from acute pancreatitis, indicated for endoscopic necrosectomy following endoscopic ultrasound (EUS)-guided drainage.
* Imaging indicative of ≥30% necrotic material within the pancreas.
* Walled-off pancreatic necrosis (WOPN) size ≥6 cm.
* Subjects able to tolerate repeated endoscopic procedures.
* Capacity for providing informed consent.
* Understanding of study requirements, provision of written informed consent, and willingness and ability to attend required follow-up assessments through 21 (+/- 7) days.

Exclusion Criteria:

* Inability to provide informed consent.
* Unwillingness to undergo repeated endoscopies.
* Presence of documented Pseudoaneurysm \> 1cm within the WOPN.
* Intervening gastric varices or unavoidable blood vessels within the access tract.
* Use of dual antiplatelet therapy or therapeutic anticoagulation that cannot be temporarily discontinued.
* Any condition deemed by the investigator to compromise the safety of undergoing an endoscopic procedure.
* Pregnancy, lactation, or absence of reliable contraception in women of childbearing potential.
* Current enrollment in another investigational trial with potential to interfere with this study's endpoint analyses.

Primary outcomes:
measure: Technical Success Rate
timeFrame: Baseline, Follow-up Visit Day 21
Secondary outcomes:
measure: Safety and Procedure-Related Adverse Events
timeFrame: Procedure Day 0, Follow-up Visit Day 21
measure: Mean Total Procedure Time
timeFrame: Procedure Day 0, Reintervention (if needed)
measure: Total Number of Reinterventions
timeFrame: From Procedure Day 0 through Follow-up Visit Day 21
measure: Clinical Improvement within 72 Hours
timeFrame: Baseline, Procedure Day 0, up to 3 days post-procedure
measure: Duration of Hospital Stay
timeFrame: From Procedure Day 0 through date of discharge
measure: Quality of Life (QOL)
timeFrame: Baseline, Follow-up Day 21
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Womens Hospital
name: Christopher C. Thompson, MD, MSc
role: PRINCIPAL_INVESTIGATOR
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