Dalargin for Prevention of Organ Disfunction in High-Risk Abdominal Surgery

NCT07404358 | Active Not Recruiting Phase 3

• 2 other identifiers: BOTKIN-DAL-PROTECT-01EC #6/25/5
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Major abdominal surgeries (e.g., gastrectomy, pancreatectomy, colectomy) carry a high risk of life-threatening postoperative complications, including multiorgan disfunction syndrome (MODS), acute kidney injur (AKI), miocardial injury after non-cardiac surgery (MINS) and severe infections. These complications are driven by ischemia-reperfusion injury, leading to oxidative stress and a systemic inflammatory response. Despite advances in surgical and anesthetic techniques, there are no effective pharmacological strategies for personalized prevention of these events, which adversely affect recovery and survival. In this context, opioid receptor agonist, particularly senthetic analogs of Leu-enkephalin such as Dalargin, have emerged as promising agents for pharmacologica preconditioning. Preclinical evidence suggests their ability to mitigate oxidative stress and inflammation by moduating key signaling pathways . The potential for these peptides to protect andothelial function and reduce organ damage presents a novel therapeutic avenue. This study aims to clinically test the hypothesis that perioperative intravenous infusion of Dalargin reduce the incidence and severity of postoperative organ dysfunction. Patients undergoing high-risk abdominal surgery will be randomized to receive either a 72-hour continuous of Dalargin (following a defined dosage regimen) or an identical placebo infusion. the study will also integrate an assessment of genetic polymorphism ( e.g., in NRF2, OLR1, TLR9 genes) to explore personalized approaches to risk stratification and prevention.

Conditions

Postoperative Complications; Multiple Organ Failure; Abdominal Surgery

Keywords

Dalargin; Leu-enkephalin; Organ protection; Pharmacological preconditioning; Oxidative stress; Genetic polymorphis; High-risk surgery

Outcome Measures

Primary Outcomes (1)

• Incidence of Major Postoperative Complications

  Composite endpoin defined as the occurrence of at leats one of the follwing within the first 7 days after surgery: Miocardial injury after non-cardiac Surgery (MINS) (defined as an elevated high-sensitivity cardiac troponin T value with an ischemic feature, without requiring ischemic symptoms), Acute Kidney Injury (according to KDIGO criteria), Acute Respiratory Distress Syndrome (according to Berlin definition) or Sepsis (according to Sepsis - 3 criteria),

  7 days postoperatively

Secondary Outcomes (11)

• Incident of acute respiratory distress syndrome (ARDS)

  7 days postoperatively

• Incidence of acute kidney injury (AKI)

  7 days postoperatively

• Incident of sepsis

  7 days postoperatively

• Plasma level of Interleukin-6 (IL-6)

  24 hours postoperatively

• Plasma level of procalcitonin

  24 hours postoperatively

Study Arms (2)

Dalargin

EXPERIMENTAL

Patients in this arm receive a continuous intravenous of the study drug Dalargin (synthetic leucine-enkephalin analog) according to the predefined protocol

Drug: Dalargin

Placebo

PLACEBO COMPARATOR

Patients in this arm recive a continious intravenous infusion of 0.9% sodium chloride as a placebo, matching the volume and administration schedule of the active arm.

Other: 0.9 % NaCl

Interventions

Dalargin DRUG

Dalargin is a synthetic analog of the endogenous opioid peptide leucine-enkephalin. It is supplied as a lyophilized powder in vials containing 30 mg. For administration, the contents of one vial are reconstituted and diluted to a total volume of 300 ml with 0,9% sodium chloride (normal saline). The solution is administered as a continious intravenous infusion via an elastomeric infusion pump. The infusion starts after induction of anesthesia and continues for a total of 72 hours according to the following regimen: 8ml/hour (delivering 0.8 mg/hour) for the first 24 hours, followed by 4 ml/hour (delivering 0.4 mg/hour) for the subsequent 48 hours.

Dalargin

0.9 % NaCl OTHER

A continious intravenous infusion of 0.9%sodium chloride used as a placebo control. It is prepared and administered in an identical manner (volume, duration, infusion device) as the active drug (Dalargin) to maintain blinding

Also known as: Normal saline, Placebo, 0.9% sodium chloride

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 to 85 years.
• Scheduled for elective high-risk abdominal surgery (e.g., gastrectome, pancreatectomy, colectomy) under general anesthesia.
• American Society of Anesthesiologists (ASA) physical status class I-III.
• Able to provide written informed consent.

You may not qualify if:

• ASA physical status class IV or V.
• Acute myocardial infarction within the past 6 month.
• Acute stroke within the past 6 month.
• Chronic heart failure NYHA class IV.
• Chronic kidney disease stage 3a or higher (according KDIGO)
• Active infectious disease.
• Any diagnosed phychiatric disorder (according ICD-10) confirmed be a psychiatrist.
• Any neuromuscular disease (according to ICD-10)
• Pregnancy or breastfeeding.
• Inability to undergo preoperative assessment.
• Previous enrollment in this trial.

Sponsors & Collaborators

• Botkin Hospital: lead

Study Sites (1)

S.P. Botkin Moscow Multidisciplinary Scientific and Clinical Center

Moscow, 125284, Russia

Location

MeSH Terms

Conditions

Postoperative Complications; Multiple Organ Failure; Spinocerebellar ataxia 23

Interventions

enkephalin-Leu, Ala(2)-Arg(6)-; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Candidate og Medical Sciences, Head of the Department of Anesthesiology and Resuscitationa №62, role in study - principal Investigator

Model Details: This is a standart parallel-group, randomized, double-blind, placebo-controlled trial. Participants are allocated in a 1:1 ratio to either the experimental intervention (Dalargin) or the placebo control group. The study follows a fixed design without adaptive elements.

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 11, 2026
• Study Start: May 13, 2025
• Primary Completion (Estimated): July 20, 2026
• Study Completion (Estimated): December 20, 2026
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)