Endothelial Dysfunction and Nitric Oxyde During Laparoscopic Surgery

NCT07638124 | Completed DMC

• 1 other identifier: ED-NOanesth
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This single-centre, pilot, prospective, randomized, open-label clinical trial evaluated the effect of intraoperative inhaled nitric oxide (iNO) on endothelial function, intestinal and renal injury biomarkers, and early clinical outcomes in high-risk cardiovascular patients undergoing prolonged laparoscopic abdominal surgery (\>120 minutes). Forty adults with cardiovascular disease and an RCRI ≥2 were randomized 1:1 to receive either iNO at 40 ppm via the ventilator circuit from post-intubation to the end of surgery or standard anaesthetic management without iNO. The primary endpoint was the 12-hour postoperative change in endothelial dysfunction markers (total nitric oxide, endothelin-1, von Willebrand factor); secondary endpoints included markers of intestinal and renal injury (I-FABP, LBP, creatinine), tissue expression of VCAM-1 and iNOS, postoperative complications, gastrointestinal recovery, and hospital length of stay.

Conditions

Laparoscopic Abdominal Surgeries

Keywords

Laparoscopic Abdominal Surgeries;; Endothelium; Nitric Oxide; Intra-Abdominal Pressure; Сardiovascular Diseases; Biomarkers

Outcome Measures

Primary Outcomes (3)

• Markers of endothelial dysfunction

  Total nitric oxide (NOtotal; sum of nitrites and nitrates, nmol/ml)

  from baseline (1 hour pre-operatively) to 12 hours postoperatively

• Markers of endothelial dysfunction

  Endothelin-1 (ET-1, fmol/ml)

  from baseline (1 hour pre-operatively) to 12 hours postoperatively

• Markers of endothelial dysfunction

  von Willebrand factor (vWF, %)

  from baseline (1 hour pre-operatively) to 12 hours postoperatively

Secondary Outcomes (5)

• Postoperative complications

  28 days

• length of hospital stay

  28 days

• Biomarkers

  12 hours

• Biomarkers

  12 hours

• Biomarkers

  12 hours

Study Arms (2)

NO group

EXPERIMENTAL

Patients receive inhaled nitric oxide at 40 ppm administered via the inspiratory limb of the anaesthesia ventilator circuit using the AIT-NO-01 "Tianox" generator (RFNC-VNIIEF, Russia). iNO is initiated immediately after tracheal intubation and continued until the end of surgery; the median iNO exposure in the pilot cohort was approximately 168 minutes. Inspired NO and NO₂ concentrations are continuously monitored according to device instructions.

Procedure: Inhaled nitric oxide at 40 ppm administered via the inspiratory limb of the anaesthesia ventilator circuit

Control group

NO INTERVENTION

Patients receive standard anaesthetic management and mechanical ventilation without iNO

Interventions

Inhaled nitric oxide at 40 ppm administered via the inspiratory limb of the anaesthesia ventilator circuit PROCEDURE

Patients receive inhaled nitric oxide at 40 ppm administered via the inspiratory limb of the anaesthesia ventilator circuit. iNO is initiated immediately after tracheal intubation and continued until the end of surgery; the median iNO exposure in the pilot cohort was approximately 168 minutes. Inspired NO and NO₂ concentrations are continuously monitored according to device instructions.

NO group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Documented cardiovascular disease, including at least one of the following: coronary artery disease, stable angina pectoris (II-III functional class), chronic heart failure (NYHA I-III), prior myocardial infarction, or cerebrovascular disease.
• Revised Cardiac Risk Index (RCRI) ≥2 (moderate/high perioperative risk).
• Scheduled for elective laparoscopic abdominal surgery (e.g., colorectal, gastric, hepatic resections) with expected duration \>120 minutes.
• Ability to provide written informed consent.

You may not qualify if:

• Pregnancy or lactation.
• Baseline methemoglobin level \>3%.
• Known hypersensitivity or contraindication to inhaled NO.
• Chronic intake of NO donors (e.g., nitroglycerin, isosorbide) or drugs known to increase methemoglobin (e.g., lidocaine, prilocaine, benzocaine).
• Severe neutropenia (neutrophils \<500/mm³) or severe thrombocytopenia (platelets \<30,000/mm³).
• Haemoglobin \<7 g/dl.
• Severe renal failure (estimated GFR \<30 ml/min/1.73 m²).
• Poorly controlled diabetes mellitus (HbA1c \>9% or frequent hypoglycaemia).
• Significant electrolyte disorders (K⁺ \<3.0 or \>5.5 mmol/l; Na⁺ \<125 or \>155 mmol/l).
• Any acute exacerbation of chronic disease on the day of surgery.
• Requirement for extracorporeal life support or other advanced organ support not compatible with protocol procedures.
• Participation in another interventional clinical trial.
• Withdrawal of consent by the patient at any point.
• Development of an allergic or severe adverse reaction to the study intervention

Sponsors & Collaborators

• Alexander Averyanov: lead
• I.M. Sechenov First Moscow State Medical University: collaborator

Study Sites (1)

First Moscow State Medical University named after I.M. Sechenov (Sechenov University)

Moscow, 119048, Russia

Location

Study Officials

• Irina A Mandel, MD, PhD

  First Moscow State Medical University named after I.M. Sechenov (Sechenov University)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The study is open-label with respect to the intervention, because iNO administration cannot be masked for the personnel delivering anaesthesia. Patients and investigators who collect and analyse clinical and laboratory data are blinded to group assignment; laboratory analyses are performed by staff unaware of treatment allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia

Study Record Dates

• First Submitted: May 31, 2026
• First Posted: June 10, 2026
• Study Start: November 19, 2024
• Primary Completion: April 24, 2026
• Study Completion: May 15, 2026
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)