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

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

Interventions

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

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.

Sponsors & Collaborators

• Botkin Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-05-13

Primary Completion

2026-07-20

Completion

2026-12-20

Countries

• Russia

Study Locations