Perioperative Nitric Oxide Prevents Acute Kidney Injury in Acute Type a Aortic Dissection Patients

Phase 4

Recruiting

• Conditions: Acute Kidney Injury; Nitrous Oxide; Acute Type a Aortic Dissection
• Interventions: Drug: Nitric Oxide; Other: Placebo

• Registration Number: NCT06622291
• Lead Sponsor: Beijing Anzhen Hospital

Brief Summary

The goal of this clinical trial is to determine the effectiveness of exogenous nitric oxide therapy in reducing the occurrence of acute kidney injury in patients with acute type A aortic dissection. Additionally, it aims to assess the safety of exogenous nitric oxide therapy.

Detailed Description

The incidence of acute kidney injury following acute type A aortic dissection is significantly high, thereby exerting a substantial impact on patient prognosis. Nitric oxide, an endogenous gaseous molecule with potential therapeutic effects, has been investigated in clinical studies as a treatment for acute kidney injury following cardiac surgery. However, there is currently no clinical study exploring the application of nitric oxide in patients with acute type A aortic dissection. Therefore, this study aims to investigate whether exogenous nitric oxide therapy has renal protective effects and its mechanism.

This prospective randomized study is conducted at Beijing Anzhen Hospital in Beijing, China. A total of 216 adult patients with acute type A aortic dissection are enrolled in this study. The patients are randomly divided into two groups: the experimental group received NO combined with conventional treatment, and the control group is only given conventional treatment. In the experimental group, 60 ppm NO is administered during intraoperative CPB and continued until within 12 hours after surgery.

The primary endpoint is the incidence of acute kidney injury (AKI). The secondary endpoints include AKI grade (KDIGO); urine volume during surgery, within 12 and 24 hours after surgery; blood flow grade, resistance index, and pulsatility index in renal ultrasound at ICU admission, 12 and 24 hours after surgery; SOFA score at 24 hours after surgery; VIS score at ICU admission, 12 and 24 hours after surgery; duration of mechanical ventilation, non-invasive ventilation, and high-flow oxygen therapy; length of ICU stay and hospital stay; renal adverse events within 90 days; volume of drainage from the pleural and pericardial cavities after surgery. Additionally, dosage of diuretics and recombinant human brain natriuretic peptide during surgery and within 48 hours after surgery; oxygenation index and near-renal infrared oxygen saturation; levels of free hemoglobin, methemoglobin, nitrite (NO2-) and the total of NO metabolites (NOt); neutrophil gelatinase-associated lipocalin concentration; levels of the neutrophils lymphocytes ratio (NLR), the platelet lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), and systemic immune response index (SII) ; CVP and PEEP, the volume of transfusions with plasma and stored or autologous RBCs will also be measured in both groups.

Study Timeline

• Study First Submitted: 2024-09-24
• Study First Submitted QC: 2024-09-27
• Status Verified: 2024-10
• Study First Posted: 2024-10-02
• Study Start: 2024-11-30
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-12
• Primary Completion: 2025-10-01
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 216

Inclusion Criteria

1. Provide written informed consent;
2. Participants must be over 18 years of age;
3. Participants should meet the diagnostic and treatment guidelines for thoracic aortic diseases jointly issued by ACC/AHA in 2022, have received clinical and radiological diagnosis of acute type A aortic dissection, and undergone surgical thoracotomy within two weeks after symptom onset.

Exclusion Criteria

1. Missing baseline value or missing postoperative serum creatinine value (Scr);
2. Preoperative eGFR less than 30ml/min/1.73m2 or receive renal replacement therapy;
3. History of kidney disease, including glomerular diseases: acute glomerulonephritis, rapidly progressive glomerulonephritis, chronic glomerulonephritis, nephrotic syndrome, etc., secondary nephropathy: lupus nephritis, diabetic nephropathy, interstitial nephritis, renal tubular disease, chronic renal failure, renal replacement therapy, etc.;
4. Previous renal tumor, kidney transplantation, and other related surgery;
5. Patients with single kidney;
6. History of malignant tumor or received radiotherapy and chemotherapy;
7. Severe skeletal muscle disease and autoimmune disease;
8. Preoperative dissection rupture or hemodynamic instability (systolic blood pressure <90mmHg);
9. Life expectancy less than 90 days;
10. Pregnant and lactating women, patients with mental disorders;
11. With intravascular or extravascular hemolytic disease;
12. Have participated in other clinical trials.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nitric Oxide	Nitric Oxide	Patients in this group receive treatment with exogenous nitric oxide (NO) via the CPB machine. After CPB, NO is administered through the inspiratory limb of the anesthetic or ventilator circuit and then via the mechanical ventilator in the ICU. Once patients are extubated, they will breathe NO through a facemask or nasal cannula. NO administration begins at the start of CPB and continues for 12 hours post-operation.
Usual care	Placebo	Patients in this group receive a sham treatment without the supply of nitric oxide during CPB and for 12 hours post-operation.

Primary Outcome Measures

Name	Time	Method
Acute kidney injury (AKI)	48 hours	Incidence of Acute Kidney injury. 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; or an increase in serum creatinine by ≥ 1.5 times compared with the initial preoperative level for seven days after intervention; or urine output \< 0.5 mL/kg/h for 6 hours during the first 48 h after surgery.

Secondary Outcome Measures

Name	Time	Method
AKI grade	48 hours after surgery	Grade I: an increase in serum creatinine ≥ 0.3 mg/dL (≥ 26.5 μM/L) during 48 hours after surgery; or an increase in serum creatinine by ≥ 1.5 times compared with the initial preoperative level for seven days after the intervention; or urine output \< 0.5 mL/kg/h for 6 hours during the first 48 h after surgery. Grade II: an increase in serum creatinine by 2-2.9 times compared with the initial preoperative level for seven days after the intervention. Grade III: an increase in serum creatinine by ≥ 3 times compared with the initial preoperative level for seven days after the intervention; or an increase in serum creatinine ≥ 4.0 mg/dL (≥ 353.6 μM/L) during 48 hours after surgery; or start RRT.
Urine output	During surgery, 12 and 24 hours after surgery	Urine output values (mL/kg/h) are assessed during CPB and 24 hours after surgery.
Vasoactive-inotropic score	immediate admission to ICU, 12 and 24 hours after surgery	Difference between groups of vasoactive-inotropic score. VIS is calculated as Dopamine dose (mg/kg/min) + Dobutamine dose (mg/kg/min) + 100 x Epinephrine dose (mg/kg/min) + 100 x Norepinephrine dose (mg/kg/min) + 10 x Milrinone dose (mg/kg/min) + 10,000 x Vasopressin dose (units/kg/min).
Neutrophil gelatinase-associated lipocalin concentration	before surgery, immediate ICU admission, 12 and 24 hours after surgery	Neutrophil gelatinase-associated lipocalin concentrations will be measured in the two groups.
Multiple organ failure	24 hours after surgery	Assessment of multiple organ failure through the Sequential organ failure score. The scoring system is mainly divided into 6 parts, namely respiratory function, coagulation function, liver, cardiovascular system, central nervous system, and renal function. The scores range from 0 to 4, with a score of 0 indicating normal function in all organs. The higher the score, the worse the prognosis.
Duration of mechanical ventilation (hours)	90 days after surgery	Difference of duration of mechanical ventilation defined as number of hours.
Duration of non-invasive ventilation and High flow oxygen therapy	90 days after surgery	Difference of duration of non-invasive ventilation and high flow oxygen therapy defined as number of hours.
ICU stay	90 days after surgery	Difference between groups of intensive care unit length of stay defined as number of days.
Hospital stay	90 days after surgery	Difference between groups of hospital length of stay defined as number of days.
Major Adverse Kidney Events	90 days after surgery	Difference between groups of major adverse kidney events at 90 days after surgery. MAKE is a composite outcome of death, new dialysis and worsened renal function (defined as a 25% or greater decline in eGFR compared to the baseline).
Postoperative pleural and pericardial drainage	24 hours after surgery	Difference values between groups of postoperative pleural and pericardial drainage.

Trial Locations

Locations (1)

Beijing Anzhen Hospital; 🇨🇳 Beijing, Beijing, China