03 Jan Early on-demand intervention versus sTandard management among acute necrotIzing pancreatitis patients coMplicated by persIsteNt orGan failure: a multi-center randomized trial

Project abbreviation: TIMING research

Overall trial start date: March 01, 2019

Overall trial end date: March13, 2024

Recruitment start date: March13, 2019

Background and Objective

The definition of “severe acute pancreatitis” is now based on the presence of “persistent organ failure” (POF) according to the Revised Atlanta classification (RAC). The RAC also defined “acute necrotic collection” (ANC) as a local pancreatic complication “containing variable amounts of both fluid and necrosis associated with necrotizing pancreatitis”. Both POF and ANC can and commonly occur early in the course of acute pancreatitis. Several guidelines state that intervention should be considered after 3-4weeks in the patients with sterile ANC. If percutaneous catheter drainage (PCD) should be performed for sterile or early infected ANC is justified in the presence of POF and when is the best timing? We have therefore framed a hypothesis that early on-demand PCD in patients with ANP, ANC, and POF will result in improved clinical outcomes. This will be tested in a randomized controlled multi-center, clinical trial designed to compare this approach with currently standard (delayed) percutaneous drainage.

Hypothesis

The hypothesis is that early on-demand PCD in patients with ANP, ANC, and POF will result in improved clinical outcomes.

Primary outcome

Death and/or major complications during the index admission (from randomization to hospital discharge or death) will be the primary endpoint. Major complications refer to new-onset organ failure (cardiovascular, renal and respiratory), bleeding requiring intervention and gastrointestinal perforation or fistula requiring intervention.

Population

In the TIMING trial, the day of onset of symptoms will be defined

as Day 0 and the second day Day 1 and so on. OF in this study will be defined as a modified Marshall score (respiratory and renal) or SOFA score＞2 (cardiovascular) for each organ system. Patients enrolled for screening will be assessed for these three organ systems on a daily basis from Day 8 to Day 21, namely, the second and the third week, to evaluate eligibility for randomization.

The inclusion criteria are:

1. Age between 18 and 70 years;

2.Able to provide informed consent;

3. Confirmed diagnosis of AP;
4. Computed tomography (CT) diagnosis of acute necrotic collection (ANC);
5. Percutaneous drainage of the ANC by ultrasound or CT guidance is technically feasible;
6. Confirmed persistent organ failure (either respiratory, renal and/or cardiovascular lasting for more than 48 h) that has not resolved by Day 7;
7. During Day 8-Day 21, meeting one or more of these criteria:

(a) New-onset organ failure not present on Day 7 (no alleviation within 24 h);

(b) Organ failure (either single or multiple, modified Marshall score or SOFA score＞2) persist for seven natural days from Day 1;

(c) Aggravation of organ failure from that on Day 7 evidenced by increased modified Marshall score or SOFA score (no alleviation within 24 h).

The exclusion criteria are:

1. Pregnant pancreatitis;
2. Chronic pancreatitis;
3. Pancreatic tumor-related pancreatitis;
4. Percutaneous or transluminal drainage or surgery is undertaken before admission(ascites drainage is permitted);
5. Patients have a history of cardio-pulmonary resuscitation during this episode;
6. Patients with a known history of severe cardiovascular, respiratory, renal or hepatic disease defined as (1) greater than New York Heart Association class II heart failure, (2) active myocardial ischemia or (3) cardiovascular intervention within previous 60 days, (4) history of cirrhosis or (5) chronic kidney disease with creatinine clearance< 40 mL/min, or (6) chronic obstructive pulmonary disease with the requirement for home oxygen