NCT07404358

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

A Randomized, Double-Blind, Placebo-Controlled Trial of Dalargin for the Prevention of Postoperative Organ Dysfunction in Patients Undergoing High-Risk Abdominal Surgery

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 200 (actual)
• Sponsor: Botkin Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is a prospective, randomized, double-blind, placebo-controlled clinical trial. The study investigates the effects of a synthetic leucine-enkephalin analog (Dalargin) on oxidative distress, systemic inflammatory response, organ failure, and infectious complications in patients undergoing high-risk abdominal surgery (e.g. on the stomach, pancreas, or colon). Objectives: The primary objective is to evaluate whether perioperative infusion of Dalargin reduces the incidence of a composite endpoint of postoperative organ dysfunction (including acute respiratory destress syndrome, acute kidney injury, and sepsis) . Secondary objectives include assessing its effects on biomarkers of oxidative stress (malondialdehyde, carbonylated proteins), inflammation (procalcitonin, interleukin-6, HMGB-1), and myocardial injury (high-sensitivity troponin T), as well asthe length of ICU and hospital stay. Methods: A total of 200 patients aged 18-85 years (ASA I-III) scheduled for elective high-risk abdominal surgery ander general anesthesia will be randomized to recieve either Dalargin or placebo (0,9% sodium chloride). The study drug will be administered as a continious intravenous: 8 ml/hour for the first 24 hour, followed be 4 ml/hour for the next 48 hours, startinf after anesthesia induction. Patient outcomes will be evaluated using clinical scales (e.g., CPIS, KDIGO, APACHE II) and laboratory assessments. Additionally, genetic polymorphismis (NRF2, OLR1, TLR9, AGTR1, AQP1) will be analyzed to identify predictors of organ dysfunction and enable personalized risk stratification. Scientific Navelty: This is the first study to comprehensively evaluate the organoprotective potential a synthetic enkephalin analog via pharmacological preconditioning in high-risk non-cardiac surgery, combining clinical endpoints with biomarker and genetic analysis to develop a personalized prevention strategy. Sample Size Justification: The sample size of 200 participants (100/group) was calculated based on the anticipated incidence of the primary composite endpoint (postoperative organ dysfunction) in the control group. Based on previous similar studies and meta-analyses, we assume an event rate of 35% in the placebo group. We hypothesize that Dalargin will reduce this incidence to 20% (absolut risk reduction of 15%). With a two-sided alpha of 0.05 and 80% power, using a chisquared test, the required sample size is 178 participants. To account for a potential dropout rate of approximately 10%, the total sample size was increased to 200 partipitants. This sample size also provides adequate power (\>80%) to detect clinically meaningful differences in key secondary endpoints, including the incidence of MINS (Myocardial Injury after non-cardiac Surgery) and changes in biomarker levels (e.g., interleukin-6)

Conditions

• Postoperative Complications
• Multiple Organ Failure
• Abdominal Surgery

Interventions

Type	Name	Description
DRUG	Dalargin	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.
OTHER	0.9 % NaCl	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

Timeline

• Start date: 2025-05-13
• Primary completion: 2026-07-20
• Completion: 2026-12-20
• First posted: 2026-02-11
• Last updated: 2026-02-11

Locations

1 site across 1 country: Russia