Nitric Oxide in Cardiopulmonary Bypass for Renal Protection in Cardiac Surgery

NCT03527381 | Completed Phase 1 DMC

• 1 other identifier: NephroNO
• Study Type: interventional
• Target: 96
• Locations: 0 countries
• Sites: N/A

Brief Summary

This prospective randomized study evaluates the nephroprotective effects of exogenous nitric oxide delivered to the extracorporeal circulation circuit during cardiac surgery with cardiopulmonary bypass.

Conditions

Coronary Artery Disease; Heart Valve Diseases; Cardiomyopathies; Acute Kidney Injury

Keywords

Cardiopulmonary Bypass; Nitric Oxide; Kidney Function Tests; Renal Insufficiency; Protective Agents; Coronary Artery Bypass; Cardiac Surgery

Outcome Measures

Primary Outcomes (1)

• Acute kidney injury rate measure

  The presence of acute kidney injury (AKI) is assessed during 48 hours after surgery. AKI is defined as follows: an increase in serum creatinine ≥ 0.3 mg/dL (≥ 26.5 μM/L) during 48 hours after surgery; an increase in serum creatinine by ≥ 1.5 times compared with the initial preoperative level for seven days after intervention; and urine output \< 0.5 mL/kg/h for 6 hours during the first 48 h after surgery.

  48 hours after surgery

Secondary Outcomes (6)

• Urine output measure

  During cardiopulmonary bypass

• Urine neutrophil gelatinase-associated lipocalin concentration measure (uNGAL)

  4 hours after surgery

• Free hemoglobin (Hb) concentration measure

  24 hours after surgery

• Nitric oxide metabolite concentration measure

  24 hours after surgery

• Proinflammatory mediator concentration measure

  24 hours after surgery

Study Arms (2)

Nitric Oxide

EXPERIMENTAL

Patients of this group receive treatment with exogenous gaseous nitric oxide supplied directly to the oxygenator in the cardiopulmonary bypass circuit during cardiac surgery.

Drug: Nitric Oxide

Standard CPB

PLACEBO COMPARATOR

Patients of this group receive sham-treatment without supplying nitric oxide to the cardiopulmonary bypass circuit (Standard CPB) during cardiac surgery. Considering dilution of nitric oxide at a high ratio of 1 to 25,000 in the gas mixture of the cardiopulmonary bypass circuit (CPB), no addition of any inert gas to the CPB circuit is required in sham-treatment group.

Other: Standard CPB

Interventions

Nitric Oxide DRUG

40 ppm of exogenous gaseous nitric oxide is supplied directly to the oxygenator in the cardiopulmonary bypass circuit during cardiac surgery.

Nitric Oxide

Standard CPB OTHER

Standard CPB protocol of delivery of air gas mixture to the cardiopulmonary bypass circuit during cardiac surgery.

Standard CPB

Eligibility Criteria

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

You may qualify if:

• Age above 18 years; planned primary cardiac intervention with cardiopulmonary bypass including coronary artery bypass grafting, valve surgery, and surgical reconstructions of the left ventricle.

You may not qualify if:

• Preoperative anemia; the intake of nephrotoxic drugs or the use of X-ray contrast within 72 h before surgery; active phase of endocarditis; emergency surgery; chronic kidney disease; hematologic diseases accompanied by hemolysis; complications of the surgery and the early postoperative period.

Sponsors & Collaborators

• Nikolay Kamenshchikov: lead

Related Publications (1)

• Kamenshchikov NO, Anfinogenova YJ, Kozlov BN, Svirko YS, Pekarskiy SE, Evtushenko VV, Lugovsky VA, Shipulin VM, Lomivorotov VV, Podoksenov YK. Nitric oxide delivery during cardiopulmonary bypass reduces acute kidney injury: A randomized trial. J Thorac Cardiovasc Surg. 2022 Apr;163(4):1393-1403.e9. doi: 10.1016/j.jtcvs.2020.03.182. Epub 2020 Jun 25.

  PMID: 32718702 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Heart Valve Diseases; Cardiomyopathies; Acute Kidney Injury; Renal Insufficiency

Interventions

Nitric Oxide

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Sergey V. Popov, MD, PhD

  Tomsk NRMC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Trial participants, data analysts, and report writers are blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Physician Anesthesiologist

Model Details: Single-center prospective, randomized, placebo-controlled study

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: May 17, 2018
• Study Start: September 1, 2015
• Primary Completion: December 25, 2016
• Study Completion: April 14, 2017
• Last Updated: January 23, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.