Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05694988 |
| Other study ID # |
efferon-ct-2022-03 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2022 |
| Est. completion date |
April 30, 2025 |
Study information
| Verified date |
February 2024 |
| Source |
Efferon JSC |
| Contact |
Alexandr Shelehov-Kravchenko, PhD, MD |
| Phone |
+79636564765 |
| Email |
alexandr.shelehov[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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 in the later stages of the disease.
In connection with a pronounced inflammatory reaction ("cytokine storm") in the early phase
of endogenous intoxication of acute pancreatitis, a promising therapeutic approach is the
extracorporeal removal of cytokines.
This prospective study intends to study the effect of hemoperfusion (Efferon CT) in
combination with high-volume hemofiltration (HVHF) on the severity of symptoms of endogenous
intoxication and indicators of organ dysfunction in acute pancreatitis.
Description:
Acute pancreatitis in emergency surgery ranks third in 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.
Mortality in patients with acute pancreatitis reaches 20-60% depending on the nature of the
disease, the phase of the pathological process, the severity of concomitant diseases, the
severity of multiple organ failure syndrome (MODS), purulent-septic complications, and the
development of septic shock. The main factors determining an unfavorable prognosis are the
frequency of multiple organ failure and the development of sepsis, their intensity, as well
as the developed septic shock. In the case of the onset and progression of multiple organ
failure in the first 48 hours, they speak of early severe pancreatitis, which is
characterized by a more unfavorable prognosis.
Acute pancreatitis is a systemic rather than a local critical condition. Associated
complications include sepsis, multiple organ failure, ARDS, acute renal failure, disseminated
intravascular coagulation syndrome, acute liver failure, etc. According to some reports, at
least 50% of deaths in the early stage of acute pancreatitis are associated with multiple
organ failure, and failure of three or more organs, mortality rises to 95%.
The moment when timely treatment can affect the outcome of the disease is often missed.
Against the background of a picture of developed pancreatic necrosis, complications arise at
lightning speed, despite the measures taken to prevent them.
The earliest possible detection of patients with an aggressive, destructive nature of the
disease is very important for the entire complex of intensive care. 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.
To date, the early pathogenetic mechanisms of acute pancreatitis and its complications have
not been sufficiently studied. 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 approach for sterile and infected pancreatic
necrosis. It is known that mortality from infected pancreatic necrosis is 2-3 times higher
than from a sterile process.
"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.
Organ hypoperfusion, tissue hypoxia, endotoxicosis, systemic inflammatory and
anti-inflammatory reactions induced by "mediator aggression" and electrolyte disturbances are
the most important links in the etiopathogenesis of acute pancreatitis and multiple organ
failure. Therefore, the use of detoxification methods aimed at removing toxic substances,
normalizing organ perfusion, reducing systemic inflammation in the treatment of patients with
acute pancreatitis is pathogenetically justified in order to prevent multiple organ failure,
pancreatic shock and sepsis.
In the last 10 years, various methods of extracorporeal detoxification have become widespread
in the practice of intensive care for severe forms of acute pancreatitis.
Nevertheless, there is no consensus among specialists regarding the timing of the application
of certain methods, taking into account the phase course of acute pancreatitis, the required
frequency of procedures and their effectiveness.
In acute pancreatitis, severe endotoxemia occurs early, leading to 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 studies have shown that the use of extracorporeal sorption methods
that eliminate pro-inflammatory cytokines improves the results of treatment of patients with
manifestations of endogenous intoxication.
Accumulated evidence in recent years suggests that continuous veno-venous hemofiltration is
beneficial in acute pancreatitis by removing inflammatory molecules and medium and low
molecular weight toxic substances by convection. Particular attention is paid to high-volume
hemofiltration, which can give a better effect in the treatment of acute pancreatitis.
The 2012 study by La-Ping Chu (China) "Clinical effects of pulsed high-volume hemofiltration
in severe acute pancreatitis complicated by multiple organ dysfunction syndrome" also
confirmed that high-volume hemofiltration has a pronounced beneficial effect on clinical
symptoms and laboratory parameters in acute pancreatitis with multiple organ failure .
In acute pancreatitis, a large number of soluble inflammatory mediators circulate in the
patient's blood. Thus, the elimination of cytotoxins with standard continuous hemofiltration
with a water exchange rate of 35 ml/kg/h may not be adequate for the severity of symptoms of
the disease. The advantage of "high volume" is the removal of substances with a higher
molecular weight, which include many inflammatory mediators. Numerous animal studies have
shown a positive effect of high volume hemofiltration (HVHF) on survival in endotoxic models.
Human studies have shown that HVHF improves hemodynamics in septic shock. But the great
concern of researchers has always been the difficulty of performing high-volume
hemofiltration as a continuous method. That is why it is of interest to study the
effectiveness of short-pulse hemofiltration techniques in acute pancreatitis.
Recently, a search is underway for new approaches to the treatment of patients in the early
stages of acute pancreatitis, even before the development of severe complications that
significantly worsen the prognosis of the disease. One of them may be the extracorporeal
removal of excessively produced inflammatory mediators (cytotoxins) from the systemic
circulation by sorption. Nevertheless, very few studies have been devoted to the use of the
hemosorption method in the early stage of acute pancreatitis, before the appearance of
purulent-septic complications.
Hemosorption is a modern method of removing from the patient's blood substances that are
toxic to body cells. Currently, there are no multicenter randomized studies confirming the
need to use extracorporeal therapy methods as one of the main areas of pathogenetic therapy
for acute pancreatitis. At the same time, there is more and more evidence of a significant
effect of an increase in the level of cytokines on the pathogenesis of the disease and its
progressive deterioration, which suggests a possible positive role of the cytokine
hemosorption method performed in the early phase of acute pancreatitis.
In connection with the above data, it seems interesting to determine the degree of influence
of the combined method of cytokine hemosorption (Efferon CT) and high-volume hemofiltration
on the clinical manifestations of endogenous intoxication and organ dysfunction in acute
pancreatitis. proceeding without septic complications.
