Coronary Artery DiseasePhase 1/2NephroNONCT03527381
Nitric Oxide in Cardiopulmonary Bypass for Renal Protection in Cardiac Surgery
A Phase 1/2 study testing Nitric Oxide and Standard CPB in people with Coronary Artery Disease and Heart Valve Diseases, run by Nikolay Kamenshchikov.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Heart Valve Diseases, Cardiomyopathies
- What is being tested?
- Nitric Oxide and Standard CPB
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2015to 14 Apr 2017
- Phase
- Phase 1/2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: Nitric Oxide Supplementation to the Extracorporeal Circulation Line as a Method of Nephroprotection in Cardiac Surgery
This prospective randomized study evaluates the nephroprotective effects of exogenous nitric oxide delivered to the extracorporeal circulation circuit during cardiac surgery with cardiopulmonary bypass.
Read the detailed description
The aim of this work is to study nephroprotective effects of nitric oxide (NO) supplementation to the cardiopulmonary bypass (CPB) circuit during cardiac surgery with normothermic CPB in adult patients. The prospective randomized study is performed in the settings of Federal Cardiology Center. A total of 96 adult patients who underwent cardiac surgery with CPB are enrolled in the study. Patients are randomized to two groups: main group receive NO treatment; control group undergoes sham procedure. In the main group, NO is supplied to the CPB line in a dose of 40 ppm throughout the entire CPB period. The primary endpoint is the frequency of acute kidney injury (AKI). The secondary endpoints are urine output during CPB; uNGAL level 4 h after surgery; plasma concentration of free hemoglobin (Hb); concentrations of NO metabolites (nitrite (NO2-) and nitrate (NO3-)) and the total concentration of metabolites of NO (NOx, μM/mL) in blood plasma in the intraoperative period; concentration of proinflammatory (TNF-α, IL-1β, -6, and -8) and anti-inflammatory mediators (IL-1ra, IL-4) in blood plasma in the intraoperative period. Cumulative fluid balance, diuresis, and Lasix doses are assessed within the first 48 h of the postoperative period. The dynamics of serum creatinine is assessed during the first week following the intervention.
- Being tested
- Nitric Oxide, Standard CPB
- Keywords
- Cardiopulmonary Bypass, Nitric Oxide, Kidney Function Tests, Renal Insufficiency, Protective Agents, Coronary Artery Bypass, Cardiac Surgery
- Medical subject headings
- Coronary Artery Disease, Heart Valve Diseases, Cardiomyopathies, Acute Kidney Injury, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
40 ppm of exogenous gaseous nitric oxide is supplied directly to the oxygenator in the cardiopulmonary bypass circuit during cardiac surgery.
Standard CPBOther
Standard CPB protocol of delivery of air gas mixture to the cardiopulmonary bypass circuit during cardiac surgery.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Standard CPB |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 hours after surgery
Secondary outcomes (6)
Urine output measure
Urine output values (mL/kg/h) are assessed during cardiopulmonary bypass (CPB).
Measured: During cardiopulmonary bypass
Urine neutrophil gelatinase-associated lipocalin concentration measure (uNGAL)
The level of uNGAL (ng/mL) is assessed 4 hours after the surgery.
Measured: 4 hours after surgery
Free hemoglobin (Hb) concentration measure
Plasma concentrations of Hg (g/L) are assessed during intraoperative period: before sternotomy, 5 minutes after aortic clamping, 5 minutes after aortic declamping, at the end of surgery, and 24 hours after surgery.
Measured: 24 hours after surgery
Nitric oxide metabolite concentration measure
Concentrations of NO metabolites (nitrite (NO2-) and nitrate (NO3-)) (μM/mL) and the total concentration of metabolites of NO (NOx) (μM/mL) in blood plasma are assessed in the intraoperative period: before sternotomy, 5 minutes after aortic clamping, 5 minutes after aortic declamping, at the end of surgery, and 24 hours after surgery.
Measured: 24 hours after surgery
Proinflammatory mediator concentration measure
Concentrations of proinflammatory (TNF-α, IL-1β, -6, and -8) (pg/mL) in blood plasma are assessed in the intraoperative period: before sternotomy, at the end of surgery, 6 hours after surgery, and 24 hours after surgery.
Measured: 24 hours after surgery
Anti-inflammatory mediator concentration measure
Concentrations of anti-inflammatory mediators (IL-1ra, IL-4) (pg/mL) in blood plasma are assessed in the intraoperative period: before sternotomy, at the end of surgery, 6 hours after surgery, and 24 hours after surgery.
Measured: 24 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2018
- Study start1 Sep 2015
- Primary completion25 Dec 2016
- Study completion14 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies 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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-center prospective, randomized, placebo-controlled study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nikolay Kamenshchikov
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nikolay Kamenshchikov, Tomsk National Research Medical Center of the Russian Academy of Sciences
- Investigators
- Sergey V. Popov, MD, PhD, Study director, Tomsk NRMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03527381
- Sponsor's protocol ID
- CRI-133/2
- Acronym
- NephroNO
- Status last verified
- Oct 2026
- First submitted
- 3 May 2018
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant data (text, tables, figures, and appendices), underlying the results of the trial, will be shared with researchers to achieve the aims in the approved proposal.
Publications
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.
PubMed 32718702