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Timing of Necrosectomy After Endoscopic Drainage of Walled-off Pancreatic Necrosis (WON)

Primary Purpose

Pancreatic Necrosis

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Endoscopic necrosectomy with step up approach
Endoscopic necrosectomy with direct approach
Sponsored by
Chinese University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Necrosis focused on measuring walled off pancreatic necrosis, endoscopic drainage, direct endoscopic necrosectomy, endoscopic step up approach

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adult (≥18 years of age) patients
  2. Diagnosis of walled-off pancreatic necrosis (WON) based on imaging criteria based on the revised Atlanta classification5
  3. Documented history of acute pancreatitis
  4. Suspected or confirmed infected WON and/or symptomatic WON causing (i) persistent pancreatic-type pain, and/or ii) gastric outlet or biliary obstruction, and/or (iii) ongoing systemic illness, anorexia, and weight loss, and/or (iv) rapidly enlarging WONs, and/or (v) infected WON*
  5. WON identified at contrast-enhanced computed tomography (CECT) and deemed amenable for EUS-guided drainage
  6. WON with a solid component >30% and/ or percentage of necrosis >= 30%

Exclusion Criteria:

  1. Previous invasive interventions for necrotising pancreatitis
  2. An acute flare up of chronic pancreatitis
  3. Recurrent acute pancreatitis
  4. Indicated for emergency laparotomy (i.e. abdominal compartment syndrome, perforation of a visceral organ, bleeding and bowel ischaemia)
  5. Contraindications to endoscopic drainage: previous total gastrectomy, gastric bypass surgery, prior surgery for pancreas-related diseases
  6. WON not adherent to the GI wall or not accessible for endoscopic drainage
  7. Coagulopathy (INR >1.5), and/or thrombocytopenia (platelets <50,000/mm3)
  8. Pregnancy

Sites / Locations

  • Royal Adelaide HospitalRecruiting
  • The Chinese University of Hong KongRecruiting
  • Medanta Institute Of Digestive & Hepatobiliary SciencesRecruiting
  • Asian Institute of GastroenterologyRecruiting
  • Deenanath Mangeshkar Hospital & Research CentreRecruiting
  • Asan Medical CentreRecruiting
  • SoonChunHyang University School of MedicineRecruiting
  • Hospital Universitario Rio HortegaRecruiting
  • King Chulalongkorn Memorial HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Endoscopic step-up approach

Direct endoscopic necrosectomy approach

Arm Description

After endoscopic drainage of WON, patients will be reassessed 72 hours after the procedure. If there is no clinical improvement 72 hours after drain placement, a CECT is performed to check the adequacy of the drainage. Irrigation of the WON via a nasocystic drain or endoscopic irrigation (step 1) is performed in case of inadequate drainage. If a nasocystic drain is inserted, 500ml of normal saline, twice a day will be used to irrigate the WON. If endoscopic irrigation is performed, only irrigation with normal saline without necrosectomy is allowed. Patients are again evaluated 72 hours after step 1. In case of improvement, treatment is conservative; otherwise step 2 will be initiated, which is endoscopic necrosectomy. Further endoscopic necrosectomy will be performed until there is clinical improvement.

Patients in the DEN group will undergo an immediate endoscopic necrosectomy after LAMS placement and balloon dilatation. A 10Fr 5cm double pigtail plastic stent will be inserted within the LAMS after necrosectomy. Patients will be assessed in 72 hours after the procedure. If there is no clinical improvement, a CECT is performed to check the adequacy of the drainage. DEN will be repeated in case of inadequate drainage. Patients will be reassessed every 72 hours and DEN repeated until there is clinical improvement. Subsequently, necrosectomy is performed weekly until a reassessment CECT at 3 weeks.

Outcomes

Primary Outcome Measures

A composite of major complications or death within 6 months after randomisation
Major complications include new onset multi-organ failure, multiple organ failure, persistent organ failure, bleeding requiring intervention, perforation of visceral organ requiring intervention, gas embolism

Secondary Outcome Measures

The individual components of the primary endpoint
The individual components include new onset multi-organ failure, multiple organ failure, persistent organ failure, bleeding requiring intervention, perforation of visceral organ requiring intervention, gas embolism
Time to resolution of WOPN
LAMS insertion to LAMS removal
Exocrine pancreatic insufficiency
Exocrine pancreatic insufficiency defined as Oral pancreatic-enzyme supplementation required to treat clinical symptoms of steatorrhea 6 months after randomization; this requirement was not present before onset of acute pancreatitis
Biliary strictures
Presence of biliary strictures on cholangiogram/ CT/ MRI
Total no. of interventions
The total number of interventions including necrosectomy or other surgical/ radiological interventions
Length of hospital
The total length of hospital stay
Recurrence of WOPN
The recurrence of WOPN detected on imaging (CT/ USG/ MRI/ EUS)
Unplanned readmissions related to WOPN
The no. of unplanned readmissions related to WOPN
Endocrine pancreatic insufficiency
Insulin or oral antidiabetic drugs required 6 months after randomization; this requirement was not present before onset of acute pancreatitis
The no. of necrosectomies
The number of necrosectomies required
Total ICU stay
No. of days for ICU stay

Full Information

First Posted
February 14, 2022
Last Updated
February 22, 2022
Sponsor
Chinese University of Hong Kong
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1. Study Identification

Unique Protocol Identification Number
NCT05252897
Brief Title
Timing of Necrosectomy After Endoscopic Drainage of Walled-off Pancreatic Necrosis (WON)
Official Title
Direct Endoscopic Necrosectomy Versus Endoscopic Step-up Approach After Endoscopic Drainage of Walled-off Pancreatic Necrosis (WON)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2022 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
June 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese University of Hong Kong

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Walled-off pancreatic necrosis (WON) is associated with a mortality of 20-30%. The current evidence supports a minimally invasive drainage approach to infected WON. The current suggested approach in international guidelines is the endoscopic step-up approach. However, recent evidence from large national cohorts support the use of direct endoscopic necrosectomy (DEN) at the time of stent placement, resulting in earlier resolution of WON and less number of necrosectomies. This study aims to investigate the clinical outcomes of the DEN versus the step-up approach for necrosectomy after endoscopic drainage of WON.
Detailed Description
INTRODUCTION Acute pancreatitis is one of the most common gastrointestinal diseases requiring emergency admissions to the hospital. 10-20% of these patients develop pancreatic necrosis and subsequent walled-off pancreatic necrosis (WON) and is associated with a mortality of 20-30%. Grade 1A evidence exists to support an initial minimally invasive drainage approach to infected WON. However, the optimal approach and timing of necrosectomy remains unaddressed. The current suggested approach in international guidelines is the endoscopic step-up approach. However, recent evidence from large national cohorts support the use of direct endoscopic necrosectomy (DEN) at the time of stent placement, resulting in earlier resolution of WON and less number of necrosectomies. OBJECTIVE This study aims to investigate the clinical outcomes of the DEN versus the step-up approach for necrosectomy after endoscopic drainage of WON. HYPOTHESIS The hypothesis is that DEN at the time of LAMS placement improves clinical outcomes after endoscopic drainage of WON as compared to the endoscopic step-up approach. DESIGN AND SUBJECTS This is a multicentre international randomized controlled trial. Patients with suspected or confirmed infected or symptomatic WON on computed tomography (CT) and who are deemed feasible for endoscopic drainage will be included in the study. Endoscopic drainage with lumen-apposing metal stents (LAMS) will be performed. Patients will be randomised to either the endoscopic step-up approach or direct endoscopic necrosectomy (DEN) approach. The primary endpoint is a composite of major complications or death within 6 months after randomisation. Secondary endpoints include time to resolution of WON, pancreatic functions, biliary strictures, need for necrosectomy, total number of interventions, length of hospital and ICU stay, recurrence of WON and unplanned readmissions related to WON. A reduction in cumulative primary endpoint with the DEN approach by 22.4% (32.2% to 9.8%) in comparison to endoscopic step-up approach was assumed. With a 2-sided significance level of 5% and power of 80%, taking into account a 5% drop-out rate, a total of 108 patients was required to demonstrate this effect. Study collaboration has been established with four other international centres. A estimation of 3 years is required to complete study recruitment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Necrosis
Keywords
walled off pancreatic necrosis, endoscopic drainage, direct endoscopic necrosectomy, endoscopic step up approach

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
randomised controlled 2 arm trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
108 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Endoscopic step-up approach
Arm Type
Active Comparator
Arm Description
After endoscopic drainage of WON, patients will be reassessed 72 hours after the procedure. If there is no clinical improvement 72 hours after drain placement, a CECT is performed to check the adequacy of the drainage. Irrigation of the WON via a nasocystic drain or endoscopic irrigation (step 1) is performed in case of inadequate drainage. If a nasocystic drain is inserted, 500ml of normal saline, twice a day will be used to irrigate the WON. If endoscopic irrigation is performed, only irrigation with normal saline without necrosectomy is allowed. Patients are again evaluated 72 hours after step 1. In case of improvement, treatment is conservative; otherwise step 2 will be initiated, which is endoscopic necrosectomy. Further endoscopic necrosectomy will be performed until there is clinical improvement.
Arm Title
Direct endoscopic necrosectomy approach
Arm Type
Active Comparator
Arm Description
Patients in the DEN group will undergo an immediate endoscopic necrosectomy after LAMS placement and balloon dilatation. A 10Fr 5cm double pigtail plastic stent will be inserted within the LAMS after necrosectomy. Patients will be assessed in 72 hours after the procedure. If there is no clinical improvement, a CECT is performed to check the adequacy of the drainage. DEN will be repeated in case of inadequate drainage. Patients will be reassessed every 72 hours and DEN repeated until there is clinical improvement. Subsequently, necrosectomy is performed weekly until a reassessment CECT at 3 weeks.
Intervention Type
Procedure
Intervention Name(s)
Endoscopic necrosectomy with step up approach
Intervention Description
Endoscopic necrosectomy will be performed with a forward-viewing gastroscope into the WON cavity. Debridement of necrotic tissue will be performed with irrigation and/or mechanical removal with endoscopic instruments. For this arm, step up approach will be adopted.
Intervention Type
Procedure
Intervention Name(s)
Endoscopic necrosectomy with direct approach
Intervention Description
Endoscopic necrosectomy will be performed with a forward-viewing gastroscope into the WON cavity. Debridement of necrotic tissue will be performed with irrigation and/or mechanical removal with endoscopic instruments. For this arm, the direct approach will be adopted.
Primary Outcome Measure Information:
Title
A composite of major complications or death within 6 months after randomisation
Description
Major complications include new onset multi-organ failure, multiple organ failure, persistent organ failure, bleeding requiring intervention, perforation of visceral organ requiring intervention, gas embolism
Time Frame
6 months
Secondary Outcome Measure Information:
Title
The individual components of the primary endpoint
Description
The individual components include new onset multi-organ failure, multiple organ failure, persistent organ failure, bleeding requiring intervention, perforation of visceral organ requiring intervention, gas embolism
Time Frame
6 months
Title
Time to resolution of WOPN
Description
LAMS insertion to LAMS removal
Time Frame
6 months
Title
Exocrine pancreatic insufficiency
Description
Exocrine pancreatic insufficiency defined as Oral pancreatic-enzyme supplementation required to treat clinical symptoms of steatorrhea 6 months after randomization; this requirement was not present before onset of acute pancreatitis
Time Frame
6 months
Title
Biliary strictures
Description
Presence of biliary strictures on cholangiogram/ CT/ MRI
Time Frame
6 months
Title
Total no. of interventions
Description
The total number of interventions including necrosectomy or other surgical/ radiological interventions
Time Frame
6 months
Title
Length of hospital
Description
The total length of hospital stay
Time Frame
6 months
Title
Recurrence of WOPN
Description
The recurrence of WOPN detected on imaging (CT/ USG/ MRI/ EUS)
Time Frame
6 months
Title
Unplanned readmissions related to WOPN
Description
The no. of unplanned readmissions related to WOPN
Time Frame
6 months
Title
Endocrine pancreatic insufficiency
Description
Insulin or oral antidiabetic drugs required 6 months after randomization; this requirement was not present before onset of acute pancreatitis
Time Frame
6 months
Title
The no. of necrosectomies
Description
The number of necrosectomies required
Time Frame
6 months
Title
Total ICU stay
Description
No. of days for ICU stay
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult (≥18 years of age) patients Diagnosis of walled-off pancreatic necrosis (WON) based on imaging criteria based on the revised Atlanta classification5 Documented history of acute pancreatitis Suspected or confirmed infected WON and/or symptomatic WON causing (i) persistent pancreatic-type pain, and/or ii) gastric outlet or biliary obstruction, and/or (iii) ongoing systemic illness, anorexia, and weight loss, and/or (iv) rapidly enlarging WONs, and/or (v) infected WON* WON identified at contrast-enhanced computed tomography (CECT) and deemed amenable for EUS-guided drainage WON with a solid component >30% and/ or percentage of necrosis >= 30% Exclusion Criteria: Previous invasive interventions for necrotising pancreatitis An acute flare up of chronic pancreatitis Recurrent acute pancreatitis Indicated for emergency laparotomy (i.e. abdominal compartment syndrome, perforation of a visceral organ, bleeding and bowel ischaemia) Contraindications to endoscopic drainage: previous total gastrectomy, gastric bypass surgery, prior surgery for pancreas-related diseases WON not adherent to the GI wall or not accessible for endoscopic drainage Coagulopathy (INR >1.5), and/or thrombocytopenia (platelets <50,000/mm3) Pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shannon Chan
Phone
852-35052627
Email
shannonchan@surgery.cuhk.edu.hk
First Name & Middle Initial & Last Name or Official Title & Degree
Anthony Teoh
Phone
852-35052627
Email
anthonyteoh@surgery.cuhk.edu.hk
Facility Information:
Facility Name
Royal Adelaide Hospital
City
Adelaide
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nam Nguyen
Email
QuocNam.Nguyen@sa.gov.au
Facility Name
The Chinese University of Hong Kong
City
Hong Kong
ZIP/Postal Code
0000
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shannon Chan
Phone
35052627
Email
shannonchan@surgery.cuhk.edu.hk
Facility Name
Medanta Institute Of Digestive & Hepatobiliary Sciences
City
Haryana
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rajesh Puri
Email
purirajesh1969@gmail.com
Facility Name
Asian Institute of Gastroenterology
City
Hyderabad
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sundeep Lakhtakia
Email
drsundeeplakhtakia@gmail.com
Facility Name
Deenanath Mangeshkar Hospital & Research Centre
City
Pune
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amol Bapaye
Email
amolbapaye@gmail.com
Facility Name
Asan Medical Centre
City
Asan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tae Jun Song
Email
drsong@amc.seoul.kr
Facility Name
SoonChunHyang University School of Medicine
City
Asan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jong Ho Moon
Email
jhmoonsch@gmail.com
Facility Name
Hospital Universitario Rio Hortega
City
Valladolid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manuel Pérez-Miranda
Email
mpmiranda5@hotmail.com
Facility Name
King Chulalongkorn Memorial Hospital
City
Bangkok
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pradermchai Kongkam
Email
kongkam@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Timing of Necrosectomy After Endoscopic Drainage of Walled-off Pancreatic Necrosis (WON)

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