Clinical trial NCT05695001: Hemoperfusion Efferon СT for the Treatment of Patients With Acute Pancreatitis
Official title: An Open Observational Prospective Pilot Study of the Efficacy and Safety of Cytokine Hemosorption Using the Efferon CT Device in Acute Endogenous Intoxication in Patients With Acute Pancreatitis and Aseptic Pancreatic Necrosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Pancreatitis With Uninfected Necrosis, Unspecified
Keywords: acute pancreatitis
sepsis
cytokine sorption
endogenous intoxication
Lead sponsor: Efferon JSC
Sponsor class: INDUSTRY
First posted: 2023-01-23
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients of both sexes over 18 years of age with signs of acute pancreatitis no later than 72 hours from the onset of an attack of pain without signs of an infectious process

Brief summary: Mortality from severe acute pancreatitis reaches 42%. The prognosis of acute pancreatitis is associated with the development of acute inflammatory response syndrome (SIRS) and multiple organ failure (MOF). Due to the lack of etiological therapy, the treatment of acute pancreatitis is predominantly symptomatic.

Severity and mortality are associated with early systemic inflammatory response syndrome (SIRS) and septic complications at a later stage of the disease.

With regard to the pronounced inflammatory response ("cytokine storm") during the early phase of endogenous intoxication of acute pancreatitis, extracorporeal removal of cytokines is a promising therapeutic approach.

This prospective study examines the effect of early extracorporeal sorption of cytokines using the Efferon CT device on the severity of clinical symptoms of endogenous intoxication in acute pancreatitis and aseptic pancreatic necrosis.

Detailed description: Acute pancreatitis in emergency surgery takes the 3rd place in terms of the frequency of its manifestation, second only to acute appendicitis and cholecystitis. The incidence of acute pancreatitis is growing from year to year and is more than 38 patients per 10,000 population per year. In 25% of patients, the development of pancreatitis is destructive.

Mortality in this pathology is mainly associated with the development of severe necrotic forms that cause a systemic inflammatory response of the body. The formation of pancreatic necrosis occurs within 1-2 days of illness, and it is at this time that the therapeutic effect is most effective. Quite often, upon admission of a patient, the severity of his condition, the data of laboratory and instrumental methods of examination do not allow us to judge the further course of the disease.

The existing systems and scales for assessing the severity of the patient APACHE II, SAPS, MODS, SOFA, Glasgow, J. Ranson and others provide an acceptable accuracy of about 80% only after 48 hours from the onset of the disease, and before that time they are of little information. This means that the severity of the condition of 20% of patients with necrotizing pancreatitis cannot be assessed in time by these systems until its clinical deterioration is obvious. Thus, often, the time when adequate treatment can affect the outcome of the disease is missed. After that, against the background of the picture of pancreatic necrosis, complications arise at lightning speed and like an avalanche, despite the measures taken to prevent them.

In this regard, the earliest identification of patients with an aggressive, destructive nature of the disease for the entire complex of intensive care seems to be very important. The severity of the patient's condition with acute pancreatitis is largely determined by the severity of endotoxemia. The latter, in turn, depends on the cytokine response of the body. "Cytokine storm", which occurs in the acute phase of pancreatitis, leads to aggravation of intoxication, inadequate and untimely correction of which underlies the development of pancreatogenic shock, multiple organ failure and septic complications.

To date, the early pathogenetic mechanisms of acute pancreatitis and its complications are poorly understood. The question of what happens at the subcellular level, what processes are responsible for the development of severe forms of the disease, extraorganic complications remains insufficiently studied.

Treatment of acute pancreatitis is traditionally divided into conservative and surgical. The start time of conservative measures, their components, an adequate assessment of effectiveness affect the timing and extent of surgical intervention.

At the moment, there is no specific surgical tactics for sterile and infected pancreatic necrosis, as well as for its purulent-septic complications. It is known that lethality from infected pancreatic necrosis is 2-3 times higher than from a sterile process.

The severity of the patient's condition with acute pancreatitis is largely determined by the severity of endotoxemia. The latter, in turn, depends on the cytokine response of the body.

In connection with the increasing spread of the "cytokine theory" in the past 10 years, various methods of extracorporeal detoxification have become widespread in the practice of intensive care for severe forms of acute pancreatitis. Despite this, there is no consensus among specialists regarding the timing of the application of certain techniques in the context of the phase course of acute pancreatitis, the required frequency of procedures, and their effectiveness.

In acute pancreatitis, severe endotoxemia occurs early, which leads to the development of multiple organ failure. Allocate biochemical, immunological and microbial components of endogenous intoxication, which include intermediate and final metabolites of the processes of autolysis and secondary infection.

Detoxification underlies the prevention and pathogenetic treatment of complications of acute pancreatitis. Numerous tests have shown that the use of extracorporeal sorption methods, the eliminirinducing pro-inflammatory cytokines, improves the results of treatment of patients with manifestations of endogenous intoxication.

Many techniques have been described - hemofiltration (HF), enterosorption, ultrahemofiltration (UHF), hemosorption (HS), plasmapheresis (PF). Very few studies have been devoted to the use of the hemosorption method in the early stage of development of acute pancreatitis, before the appearance of septic complications.

Recently, there has been a search for new approaches to the treatment of patients in the early stages of pancreatitis, even before the development of formidable complications, significantly worsening the prognosis of the disease. One of them may be extracorporeal removal from the systemic circulation of excessively produced mediators of the inflammatory response (cytokines) by hemosorption.

Hemosorption is the most modern method of removing substances toxic to body cells from the patient's blood. The procedure is carried out outside the body by pumping the blood flow through a column filled with a sorbent (hemoperfusion procedure). Critical parameters for therapeutic efficacy are the type of sorbent, its volume, the number of repeated procedures; they are individualized depending on the identified pathological disorders and the patient's condition.

Currently, there are no multicenter randomized studies confirming the need for extracorporeal blood purification methods as one of the main areas of pathogenetic therapy for acute pancreatitis. At the same time, the increasing emergence of data on the significant influence of the "cytokine storm" on the pathogenesis of the disease and its progressive deterioration suggests a possible positive role of the cytokine hemosorption method performed in the early phase of acute pancreatitis.

Efferon CT (JSC Efferon, Moscow, Russia) is a device for extracorporeal blood purification using direct hemoperfusion. Detoxification is carried out by sorption of cytokines and other products of endogenous intoxication with a molecular size of up to 55 kDa.

In connection with the above data, the purpose of this clinical study is to determine the degree of influence of the use of the hemosorption device Efferon CT (JSC Efferon, Russia) on the clinical manifestations and laboratory parameters of acute pancreatitis occurring without septic complications.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years old,
* Verified diagnosis of "Acute pancreatitis" according to the Atlanta classification of acute pancreatitis (2012), without signs of infection,
* No more than 72 hours from the onset of an attack of acute pancreatitis to hemosorption,
* The patient's condition allows for therapy with the Efferon CT device for at least 4 hours.

Exclusion Criteria:

* History of chronic pancreatitis (exacerbation of chronic pancreatitis),
* The presence of a focus of non-sanitized surgical infection,
* The use of other methods of extracorporeal removal of inflammatory mediators in the treatment of pancreatitis (hemofilters with highly permeable and surface-modified membranes),
* Inability to achieve or maintain a minimum mean arterial pressure (MAP) ≥ 65 mmHg. Art., despite vasopressor therapy and infusion therapy for 24 hours,
* End-stage renal disease, and the need for chronic dialysis,
* Acute pulmonary embolism,
* Transfusion reaction,
* Severe congestive heart failure,
* The patient has had an acute myocardial infarction within the last 4 weeks,
* Uncontrolled bleeding (acute blood loss in the last 24 hours),
* Severe granulocytopenia (white blood cell count less than 500 cells/mm3) or severe thrombocytopenia,
* Oncopathology out of remission.

Primary outcomes:
measure: Effect of Efferon CT hemoperfusion on SOFA scores (Sequential Organ Failure Assessment) in patients with acute pancreatitis.
timeFrame: 1-72 hours
Secondary outcomes:
measure: The effect of Efferon CT hemoperfusion on length of stay in the intensive care unit
timeFrame: 1-14 days
measure: Effect of Efferon hemoperfusion on interleukin levels (IL-1b, IL-6, IL-8, IL-10, IL-18)
timeFrame: 1-72 hours
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: N.V. Sklifosovsky Moscow Research Institute of Emergency
Study officials:
affiliation: N. V. Sklifosovsky Moscow Research Institute of Emergency, Moscow, Russia
name: Vladimir Kiselev, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: