Condition category
Digestive System
Date applied
21/01/2020
Date assigned
23/01/2020
Last edited
31/01/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Acute necrotic collection (ANC) is one of the complications of acute pancreatitis. In patients with persistent organ failure (POF), namely, the most severe type of AP patients, ANC is very common and it is controversial that if early invasive intervention before confirming infection is beneficial in this entity. Based on the previous studies, most ANC could be well absorbed or demarcated naturally, and percutaneous drainage may lead to bacterial colonization or infection of pancreatic necrosis. So it was suggested to delay intervention in asymptomatic patients. However, considering the pathophysiology of SAP, despite the sterile nature, ANC always contains numerous enzymes and inflammatory mediators, which play important roles in the development of POF and SIRS. It is controversial whether a delayed strategy in patients showing clinical deterioration before clear signs or evidence of infection is beneficial or could even worsen the outcomes. The aim of this study is to compare the effect of organ function-directed and infection-directed intervention in patients with ANC combined with POF (more than a week).

Who can participate?
All adult patients admitted with a primary diagnosis of acute pancreatitis and persistent organ failure to the participating hospital of the Chinese Acute Pancreatitis Clinical Trials Group will be assessed for eligibility on a daily basis during their hospital stay.

What does the study involve?
Patients are randomly allocated to receive either organ function-directed or infection-directed intervention.

What are the possible benefits and risks of participating?
Participants may get some clinical benefit from the trial and some advice from doctors.

Where is the study run from?
Jinling Hospital affiliated to Nanjing University (China)

Who is funding the study?
Jiangsu Province Key Research and Development Program (Social Development) Project (China)

Who is the main contact?
1. Dr Dong Xiaowu
dxw2333@163.com
2. Dr Tong Zhihui
njzyantol@hotmail.com

Trial website

Contact information

Type

Public

Primary contact

Mr Xiaowu Dong

ORCID ID

https://orcid.org/0000-0002-5717-5384

Contact details

305 Zhongshan Road East
Nanjing
210000
China
+86 (0)18512523817
dxw2333@163.com

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

2018NZKY-009-01

Study information

Scientific title

Infection-directed versus organ-function-directed intervention in acute necrotizing pancreatitis complicated with persistent organ failure: a pilot study

Acronym

Study hypothesis

Current study hypothesis as of 31/01/2020:
For severe acute pancreatitis patients complicated with acute necrotic collection and persistent organ failure in the early stages of disease, organ function-directed interventions may improve patient organ function and prognosis. This pilot study aimed to compare the effect of organ function-directed and infection-directed intervention.

Previous study hypothesis:
For severe acute pancreatitis patients complicated with acute necrotic collection and persistent organ failure in the early stages of disease, organ function-directed interventions may improve patient organ function and prognosis. This randomized, controlled, multi-center study aimed to compare the effect of organ function-directed and infection-directed intervention.

Ethics approval

Approved 16/04/2018, Clinical trial ethics committee of the General Hospital of the Eastern Theater (305 Zhongshan Road East, Nanjing, Jiangsu, China; +861 (0)25-80863234; wuqiong80863234@163.com), ref: 2018NZKY-009-01

Study design

Randomized controlled open-label pilot trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a participant information sheet

Condition

Acute pancreatitis

Intervention

Current interventions as of 31/01/2020:
Randomization will occur in a 1:1 fashion with computer-generated random numbers.

Organ function-directed group:
In addition to the standard treatment, ultrasound or CT guided percutaneous drainage would be applied once meeting one of the following conditions:
1. New-onset organ failure (no alleviation within 24 hours)
2. Unalleviated organ failure (either single or multiple, modified Marshall score ≥2) lasting for at least 7 days after randomization
3. Aggravation of organ failure from the baseline (either single or multiple) evidenced by increased modified Marshall score (no alleviation within 24 hours)

Infection-directed group:
Intervention including catheter drainage and necrosectomy would be delayed until suspicion or diagnosis of pancreatic infection and preferably after encapsulation of the necrotic collection (after 4 weeks mostly).

Previous interventions:
Randomization will occur in a 1:1 fashion for each center (sample size of each center was predefined based on its volume) with computer-generated random numbers.

Organ function-directed group:
In addition to the standard treatment, ultrasound or CT guided percutaneous drainage would be applied once meeting one of the following conditions:
1. New-onset organ failure (no alleviation within 24 hours)
2. Unalleviated organ failure (either single or multiple, modified Marshall score ≥2) lasting for at least 7 days after randomization
3. Aggravation of organ failure from the baseline (either single or multiple) evidenced by increased modified Marshall score (no alleviation within 24 hours)

Infection-directed group:
Intervention including catheter drainage and necrosectomy would be delayed until suspicion or diagnosis of pancreatic infection and preferably after encapsulation of the necrotic collection (after 4 weeks mostly).

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

1. All-cause mortality in hospital according to the medical records at the time of discharge
2. Major complications, including organ failure measured using Revised Marshall Score at baseline and daily during observation, complications such as infected pancreatic necrosis, sepsis, abdominal bleeding and fistulas according to diagnosis based on CT, bacterial culture results or the symptoms of the patients

Secondary outcome measures

1. Incidence and timing of infected pancreatic necrosis according to diagnosis based on CT, bacterial culture results or the symptoms of the patients
2. Incidence and timing of sepsis according to diagnosis based on CT, bacterial culture results or the symptoms of the patients
3. Incidence and timing of other common complications such as abdominal bleeding and fistulas according to diagnosis based on CT or the symptoms of the patients
4. Requirement of open surgery taken from the medical records at the time of discharge
5. ICU duration taken from the medical records at the time of discharge
6. Hospital duration taken from the medical records at the time of discharge
7. Total cost taken from billing system at the time of discharge

Overall trial start date

01/06/2016

Overall trial end date

01/05/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Symptoms and signs of acute pancreatitis based on abdominal pain suggestive of AP, serum amylase at least three times the upper limit of normal, and/or characteristic findings of AP on computed tomography
2. The duration of disease up to 1 week (starting with abdominal pain)
3. Confirmed persistent organ failure (respiratory, circulatory, renal) failure (revised Marshall score ≥ 2 points and the duration of up to 48 hours)
4. Age between 18 to 70 years old
5. Necrotic collection with available routes for ultrasound or CT guided percutaneous no matter sterile or infected

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

100

Total final enrolment

30

Participant exclusion criteria

1. Pregnant
2. Chronic pancreatitis, recurrent acute pancreatitis or pancreatic tumor-related pancreatitis
3. Percutaneous or transluminal drainage or surgery undertaken before admission
4. Previous history of cardio-pulmonary resuscitation
5. History of severe cardiovascular, respiratory, renal, hepatic, hematologic, or immunologic disease defined as:
5.1. Greater than New York Heart Association class II heart failure
5.2. Active myocardial ischemia
5.3. Cardiovascular intervention within the previous 60 days
5.4. History of cirrhosis
5.5 Chronic kidney disease with creatinine clearance< 40 mL/min
5.6 Chronic obstructive pulmonary disease with requirement for home oxygen

Recruitment start date

02/07/2018

Recruitment end date

12/08/2019

Locations

Countries of recruitment

China

Trial participating centre

Jinling Hospital affiliated to Nanjing University
305 Zhongshan Road East
Nanjing
210000
China

Sponsor information

Organisation

Jinling Hospital affiliated to Nanjing University

Sponsor details

305 Zhongshan Road East
Nanjing
210000
China
+86 (0)13851948781
njzyantol@hotmail.com

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Jiangsu Province Key Research and Development Program (Social Development) Project (BE2016749)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Intention to publish date

31/12/2020

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

31/01/2020: This is a pilot study followed by the TIMING study (ISRCTN91106416). The following changes have been made: 1. The public title has been changed from "A multi-center randomized controlled study of interventions in severe acute pancreatitis patients complicated with acute necrotic collection and persistent organ failure" to "A comparison of different strategies for early severe acute pancreatitis". 2. The scientific title has been changed from "InfEction-directed Versus Organ-function-directed intervention for acute necrotic coLlection in severe acUte pancreaTitis complIcated with persistent OrgaN failure: a multi-center randomized trial (EVOLUTION trial)" to "Infection-directed versus organ-function-directed intervention in acute necrotizing pancreatitis complicated with persistent organ failure: a pilot study". 3. The acronym "EVOLUTION" has been removed. 4. The study design has been changed from "Multi-center randomized controlled open-label trial" to "Randomized controlled open-label pilot trial". 4. The intervention has been updated. 5. The study hypothesis has been updated. 6. The trial participating centre The First Affiliated Hospital of Nanchang University has been removed. 7. The trial participating centre Xiang Ya Hospital Zhongnan University has been removed. 8. The trial participating centre Sir Run Run Shaw Hospital affiliated with the Zhejiang University School of Medicine has been removed. 9. The trial participating centre Xijin Hospital of the Fourth Military Medical University has been removed. 10. The plain English summary has been updated to reflect these changes. 22/01/2020: Trial's existence confirmed by Clinical trial ethics committee of the General Hospital of the Eastern Theater.