Perioperative Nitric Oxide Prevents Acute Kidney Injury in Cardiac Surgery Patients With Chronic Kidney Disease

NCT05757557 | Completed Phase 1 DMC

• 1 other identifier: DEFENDER
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

The protective nitric oxide (NO) effects are mediated by selective pulmonary vasodilation and improvement of arterial oxygenation in hypoxemic patients by reducing intrapulmonary shunting and improving ventilation-perfusion coordination. Inhaled NO has been used for years to treat acute respiratory failure and pulmonary hypertension in anesthesia and intensive care. The nephroprotective role of NO was studied in an experimental model of contrast-induced nephropathy. The primary aim of this prospective, double-blind, randomized, parallel-group, controlled trial is to test the hypothesis that perioperative conditioning of patients with NO at a dose of 80 ppm, obtained by plasma-chemical synthesis technology, through a ventilator and an extracorporeal circulation circuit reduces the incidence of acute kidney injury (AKI) in patients with an initially high risk of kidney damage due to the presence of preoperative chronic kidney disease (CKD). The study is interventional. Examination and treatment of patients is carried out in accordance with the approved standards of medical care for the relevant diseases. During the study, no experimental or unregistered (not approved for use) medical or diagnostic procedures in the territory of the Russian Federation will be carried out. The study includes patients admitted to the Cardiac Surgery Department of Cardiology Research Institute of Tomsk NRMC for elective surgery with high risk of AKI in the perioperative period

Conditions

Acute Kidney Disease; Chronic Kidney Disease; Cardiac Surgery; Cardiopulmonary Bypass

Keywords

Acute Kidney Disease; Nitric Oxide; Chronic Kidney Disease; Cardiopulmonary Bypass; Cardiac Surgery; Prevention

Outcome Measures

Primary Outcomes (1)

• Incidence of AKI (%)

  Difference between groups in the incidence of AKI in patients with CKD are assessed as percentage after cardiac surgery according to KDIGO criteria.

  7 days

Secondary Outcomes (23)

• Incidence of low cardiac output syndrome (%)

  24 hours

• Regional tissue oxygen saturation levels (rSO2, %)

  24 hours

• ΔPCO2/ΔContO2 (ratio)

  24 hours

• AKI Severity (degree)

  7 days

• AKI duration (hours)

  Seven days

Other Outcomes (3)

• Subclinical AKI

  24 hours

• Subclinical intestinal injury

  24 hours

• Subclinical myocardial damage

  24 hours

Study Arms (2)

Control group

ACTIVE COMPARATOR

Oxygen-air mixture without NO after intubation, during CPB, and six hours after surgery.

Drug: Sham treatment

80-ppm NO

EXPERIMENTAL

NO will be supplemented at 80-ppm concentration to cardiac surgery patients perioperative after trachea intubation, during CPB, and six hours after surgery.

Drug: 80-ppm NO

Interventions

Sham treatment DRUG

Sham treatment: Oxygen-air mixture without NO after intubation, during CPB, and for six hours after surgery.

Also known as: Oxygen-Air Mixture

Control group

80-ppm NO DRUG

NO will be supplemented at 80-ppm concentration to cardiac surgery patients perioperatively after trachea intubation, during CPB, and for six hours after surgery.

Also known as: Nitric Oxide

80-ppm NO

Eligibility Criteria

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

You may qualify if:

• Cardiac surgery with CPB
• Age \> 18 years
• Signed informed consent
• CKD (cGFR \<60 mL/min/1.73 m2)
• Positive decision of council of physicians on individual safety of perioperative administration of NO

You may not qualify if:

• Emergency surgery (including that in ACS)
• cGFR \<15 mL/min/1.73 m2
• Administration of potentially nephrotoxic drugs within 24 hours before surgery (radiocontrast agents, antimicrobial therapy with aminoglycosides and / or amphotericin)
• Critical preoperative status (preoperative need for mechanical ventilation, inotropes, circulatory support)
• Pregnancy
• Ongoing enrolment in other randomized clinical trial
• Previous randomization in DEFENDER trial
• Active endocarditis and/or sepsis
• Pulmonary hypertension higher than stage II (systolic pulmonary pressure over 65 mmHg according to data of preoperative transthoracic echocardiography
• Condition after kidney transplantation
• Ongoing AKI caused by glomerulonephritis, interstitial nephritis, renal artery occlusion, or postrenal occlusion
• Cardiac surgery with hypothermic circulatory arrest
• Left ventricular ejection fraction \< 30%
• Single kidney

Sponsors & Collaborators

• Tomsk National Research Medical Center of the Russian Academy of Sciences: lead

Study Sites (1)

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Tomsk, Russia, 634012, Russia

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Nitric Oxide

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals

Study Officials

• Nikolay O Kamenshchikov, MD, PhD

  Cardiology Research Institute, Tomsk National Research Medic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Head of Laboratory

Study Record Dates

• First Submitted: February 11, 2023
• First Posted: March 7, 2023
• Study Start: February 25, 2023
• Primary Completion: December 31, 2024
• Study Completion: January 31, 2025
• Last Updated: April 10, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Proposals may be submitted up to 36 months following publication of the results of the trial. After 36 months, the data will be available in the Center's data ware house but without investigator support other than deposited metadata.
• Access Criteria: Information regarding submitting proposals and accessing data may be requested from the principal investigator by e-mail.

Locations

RU (1)