Postoperative ComplicationsPhase 3Dal-PROTECTNCT07404358
Dalargin for Prevention of Organ Disfunction in High-Risk Abdominal Surgery
A Phase 3 study testing Dalargin and 0.9 % NaCl in people with Postoperative Complications and Multiple Organ Failure, run by Botkin Hospital at 1 site in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Postoperative Complications, Multiple Organ Failure, Abdominal Surgery
- What is being tested?
- Dalargin and 0.9 % NaCl
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteRussia
- Study dates
- 13 May 2025to 10 Sep 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Russia1 site
S.P. Botkin Moscow Multidisciplinary Scientific and Clinical Center
Moscow, 125284
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Trial of Dalargin for the Prevention of Postoperative Organ Dysfunction in Patients Undergoing High-Risk Abdominal Surgery
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.
Read the 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)
- Being tested
- Dalargin, 0.9 % NaCl
- Keywords
- Dalargin, Leu-enkephalin, Organ protection, Pharmacological preconditioning, Oxidative stress, Genetic polymorphis, High-risk surgery
- Medical subject headings
- Postoperative Complications, Multiple Organ Failure, Spinocerebellar ataxia 23
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DalarginDrug
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.
0.9 % NaClOther
Also called Normal saline, Placebo, 0.9% sodium chloride
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
| Study group | Role | What they receive |
|---|---|---|
| Dalargin | Experimental | Patients in this arm receive a continuous intravenous of the study drug Dalargin (synthetic leucine-enkephalin analog) according to the predefined protocol Receives: 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. Receives: Other: 0.9 % NaCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
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),
Measured: 7 days postoperatively
Secondary outcomes (11)
Incident of acute respiratory distress syndrome (ARDS)
Diagnosed according to the Berlin Definition (timing, origin, chest imaging, oxygenation)
Measured: 7 days postoperatively
Incidence of acute kidney injury (AKI)
Defined and staged according to the kidney disease: improving Global Outcomes (KDIGO) criteris, based on serum creatinine and urine output.
Measured: 7 days postoperatively
Incident of sepsis
Defined accorging to hte Sepsis-3 criteria as a life-threatening organ dysfunction caused by a dysregulated host response to infection
Measured: 7 days postoperatively
Plasma level of Interleukin-6 (IL-6)
Concentration measured in picograms per milliliter (pg/ml) using enzyme-linked immunosorbent assay (ELISA).
Measured: 24 hours postoperatively
Plasma level of procalcitonin
Concentration measured in nanograms per milliliter (ng/ml)
Measured: 24 hours postoperatively
Length of intensive care unit (ICU) stay
Total number of days spent in ICU from the day of surgery until discharge
Measured: From surgery until ICU discharge, up to 30 days
Length of hospital stay
Total numbers of days spent in the hospital from the day of surgery until discharge.
Measured: From surgery until hospital discharge, 30 days.
30-days all-cause mortality
Death from any cause occurring within 30 days after the index surgery
Measured: 30 days postoperatively
Incidence of postoperative delirium
Assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the 3-Minute Diagnostic Interview for (3D-CAM)
Measured: 7 days postoperatively
Level of oxidative stress marker (Malondialdehyde, MDA)
Plasma concentration of malondialdehyde measured in micromoles per liter as a marker of lipid peroxidation
Measured: 2 days postoperatively
Chande in insulin resistance (HOMA-IR)
Change in the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index from baseline to the postoperative period.
Measured: 5 days postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2026
- Study start13 May 2025
- Primary completion10 Sep 2026
- Study completion10 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative ComplicationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Botkin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anatolii Anatolievich Malyshev, Botkin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07404358
- Sponsor's protocol ID
- BOTKIN-DAL-PROTECT-01
- Other IDs
- EC #6/25/5
- Acronym
- Dal-PROTECT
- Status last verified
- Sep 2026
- First submitted
- 5 Feb 2026
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Trial of Dalargin for the Prevention of Postoperative Organ Dysfunction in Patients Undergoing High-Risk Abdominal Surgery
- ClinicalTrials.gov ID
- NCT07404358
- Acronym / sponsor ID
- Dal-PROTECT / BOTKIN-DAL-PROTECT-01
- Keywords
- Dalargin, Leu-enkephalin, Organ protection, Pharmacological preconditioning, Oxidative stress, Genetic polymorphis, High-risk surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Botkin HospitalUniversity, hospital or other
- Study start
- 13 May 2025 (actual)
- Primary completion
- 10 Sep 2026 (actual)
- Study completion
- 10 Sep 2026 (actual)
- First posted
- 11 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dalargin | Experimental | Drug: DalarginPatients in this arm receive a continuous intravenous of the study drug Dalargin (synthetic leucine-enkephalin analog) according to the predefined protocol |
| Placebo | Placebo comparator | Other: 0.9 % NaClPatients 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DalarginDalargin 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. | Drug | Dalargin |
| 0.9 % NaClAlso: Normal saline, Placebo, 0.9% sodium chlorideA 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 | Other | Placebo |
Primary outcome
Incidence of Major Postoperative Complications
Time frame: 7 days postoperatively
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),
11 secondary outcomes
Incident of acute respiratory distress syndrome (ARDS)
Time frame: 7 days postoperatively
Incidence of acute kidney injury (AKI)
Time frame: 7 days postoperatively
Incident of sepsis
Time frame: 7 days postoperatively
Plasma level of Interleukin-6 (IL-6)
Time frame: 24 hours postoperatively
Plasma level of procalcitonin
Time frame: 24 hours postoperatively
Length of intensive care unit (ICU) stay
Time frame: From surgery until ICU discharge, up to 30 days
Length of hospital stay
Time frame: From surgery until hospital discharge, 30 days.
30-days all-cause mortality
Time frame: 30 days postoperatively
Incidence of postoperative delirium
Time frame: 7 days postoperatively
Level of oxidative stress marker (Malondialdehyde, MDA)
Time frame: 2 days postoperatively
Chande in insulin resistance (HOMA-IR)
Time frame: 5 days postoperatively
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dalargin and 0.9 % NaCl in people with Postoperative Complications and Multiple Organ Failure, run by Botkin Hospital at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Major Postoperative Complications (time frame: 7 days postoperatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.