High-dose Inhaled NO Therapy for the pREvention of nosoCOmial Pneumonia After Cardiac Surgery Under caRDiopulmonary Bypass
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Incidence of nosocomial pneumonia (percent)
研究概览
简要总结
The primary aim of this single-center, prospective, randomized, controlled, study is to test the hypothesis that inhalation of NO 200 ppm prevents the development of nosocomial pneumonia in patients at risk after cardiac surgery under CPB. 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 National Research Medical Center for elective surgery with CPB.
详细描述
NOSOCOMIAL PNEUMONIA AFTER CARDIAC SURGERY WITH CADIOPULMONARY BYPASS. Nosocomial pneumonia (NP) is one of the most common complications of cardiac surgery with cardiopulmonary bypass (CPB), its frequency according to various sources ranges from 2 to 10% . This complication is accompanied by higher mortality (0.7-4% in patients without pneumonia vs. 25.1-28.2% in patients with pneumonia) , prolonged hospital stay and increased economic costs. In the retrospective analysis of medical histories of patients operated on CPB for 2020, 2021 and 2022, 3 main risk factors for the development of NP in the postoperative period were identified: time of CPB ≥ 96 minutes, duration of mechanical ventilation ≥ 14 hours, and the presence of atrial fibrillation (AF) before surgery. STUDY NATURE In relation to medical procedures, this study is observational. The examination and treatment of patients will be carried out in accordance with the approved standards of medical care for the respective diseases. In this study, no experimental or unregistered (not approved for use) medical or diagnostic procedures on the territory of the Russian Federation will be carried out. STUDY TYPE Single-center, prospective, double-blind, randomized, controlled, parallel group study. STUDY OBJECTIVES PRIMARY OBJECTIVE OF THE STUDY To test the hypothesis that inhalation of NO 200 ppm prevents the development of NP in patients after cardiac surgery under CPB and has a positive effect on the structural and functional state of the external respiration.
SECONDARY OBJECTIVES OF THE STUDY
- To test the hypothesis that inhalation of NO 200 ppm twice a day for 30 minutes for 5 days is safe for patients.
- To test the hypothesis that prophylactic inhalation of NO 200 ppm twice a day for 30 minutes increases the duration of manifestation of nosocomial pneumonia (in case of its development) after cardiac surgery under CPB.
- To test the hypothesis that prophylactic inhalation of NO 200 ppm twice a day for 30 minutes reduces the time of resolution of NP (in case of its development) after cardiac surgery under CPB.
- To assess the differences in pulmonary function according to the 6-minute walk test (6MWT), spirometry and ergospirometry and their dynamics in the main and control groups.
- To assess the morphological picture of the lungs and its dynamics according to lung ultrasound in the main and control groups.
- To compare the level of acute phase reactants and their dynamics in the main and control groups.
- To compare plasma levels of surfactant proteins SP-D and sRAGE and their dynamics in the main and control groups.
RATIONALE FOR RANDOMIZATION There is currently no convincing evidence of benefits or harms of NO inhalation as part of the prevention of NP after cardiac surgery with CPB. Thus, there is no reason to believe that randomization to study groups creates additional risks / benefits for patients. Nevertheless, regardless of the results of randomization, the decision on the possibility of prophylactic NO inhalation after cardiac surgery in each case will be made by a special medical commission consisting of a cardiac surgeon, anesthesiologist and cardiologist, immediately after the patient is enrolled in the study.
PATIENT RANDOMIZATION Patients eligible for this study will be randomized to the intervention group (NO group) and Control group in a 1: 1 ratio according to the randomization sequence generated by a computer program with random numbers by 80 people in each group. Patients will be randomized immediately after screening and signing the informed consent. Patients in both groups will not receive NO outside of the study protocol until discharged from the hospital. Patient randomization will be performed by a non-blinded NO delivery investigator who is not involved in the clinical management of the patient and the evaluation of treatment outcomes. Patients in the intervention group will receive inhaled NO therapy at a dose of 200 ppm 2 times a day for 5 days or until pneumonia is detected. In the control group, instead of inhaled NO therapy, patients will receive "Sham treatment": similar equipment and observation protocol during the intervention will be used as in the main group, but NO will not be added to the delivered gas mixture. BLINDING The gas supply systems will look the same for patients of both NO group and Control group. Patients, treating physicians, investigators and other professionals involved in the interpretation of the results will not be aware of the nature of the therapy until the end of the study. The investigating doctor who is responsible for the delivery and monitoring of the investigated gas will remain unblinded and will be responsible for blinding the gas delivery systems, monitoring and securing the delivery, and maintaining the randomization codes. Randomization codes will be sealed in sequentially numbered opaque envelopes. The sequential envelope numbers will serve as randomization numbers that will be recorded in patient's case report form (CRF) and used when necessary, for example, to treat complications. DOSAGE REGIMEN AND DURATION OF THERAPY When choosing the dose and timing of NO exposure, clinicians should be guided by 2 basic principles:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cardiac surgery with CPB at current hospitalization.
- •Age > 18 years.
- •Signed informed consent
排除标准
- •Emergency surgery.
- •Acute coronary syndrome 30 days before surgery.
- •Surgery for active infective endocarditis requiring antibiotic therapy.
- •Diagnosed infectious process of another localization (surgical site infection (SSI), acute and chronic urinary tract infection (active), catheter-related bloodstream infection, peritonitis, etc.).
- •Taking antibacterial drugs for 14 days preceding surgery
- •Other complications of the postoperative period (pneumothorax requiring pleural drainage, perioperative myocardial infarction accompanied by pulmonary edema, shock of any etiology during the current hospitalization).
- •Potentially dialysis-dependent stage 2 and higher acute kidney injury (according to KDIGO) in the early postoperative period (the criteria for potentially dialysis-dependent acute kidney injury will include patients with stage 2 acute kidney injury and: oliguria against the background of normo-hypervolemia and resistance to loop diuretics and/ or oliguria against the background of conducting infusion therapy due to hypovolemia and resistance to loop diuretics).
- •Continued mechanical ventilation.
- •Presence of tracheostomy.
- •Patient's participation in another clinical trial at the time of screening or within the previous 3 months.
- •Concomitant pulmonary disease with the need for respiratory support before surgery.
- •History of malignancy or other irreversible diseases/conditions with a 6- month mortality rate >50%.
研究组 & 干预措施
200 ppm
NO will be supplemented at 200-ppm concentration after extubation within 5 days after surgery 2 times a day for 30 min
干预措施: 200-ppm NO (Drug)
Control group
Oxygen-air mixture without NO after extubation within 5 days after surgery 2 times a day for 30 min
干预措施: Sham treatment (Drug)
结局指标
主要结局
Incidence of nosocomial pneumonia (percent)
时间窗: From the date of randomization until the date of discharge from hospital (from 2 to 4 weeks)
The difference in the incidence of nosocomial pneumonia development (percent).
次要结局
- Interleukin-6 (IL-6) levels (pg/mL)(7 days from the date of randomization)
- Interleukin-8 (IL-8) levels (pg/mL)(7 days from the date of randomization)
- Forced vital capacity (L)(7 days from the date of randomization)
- VE-minute ventilation (L/min)(10 days from the date of randomization)
- PetO2 - partial pressure of oxygen in exhaled air (mm Hg)(10 days from the date of randomization)
- PetCO2 - partial pressure of carbon dioxide in exhaled air (mmHg)(10 days from the date of randomization)
- Exhaled NO levels (ppm)(Every day from the date of randomization until day 7)
- Heart rate (HR) (bpm)(Every day from the date of randomization until day 7)
- Respiratory rate (RR) (brpm)(Every day from the date of randomization until day 7)
- Saturation of peripheral oxygen (SpO2) levels (percentage)(Every day from the date of randomization until day 7)
- Total leukocyte counts (10*9/L)(7 days from the date of randomization)
- Asymmetric dimethylarginine (ADMA) levels (ng/mL)(7 days from the date of randomization)
- Immature cell counts (percentage)(7 days from the date of randomization)
- C-reactive protein (CRP) level (mg/L)(7 days from the date of randomization)
- PCT (procalcitonin) test (ng/mL)(7 days from the date of randomization)
- Presepsin levels (pg/mL)(7 days from the date of randomization)
- Ferritin levels (ng/mL)(7 days from the date of randomization)
- LDH (lactate dehydrogenase) levels (IU/L)(7 days from the date of randomization)
- Vascular endothelial growth factor A (VEGF-A) levels (pg/mL)(7 days from the date of randomization)
- Angiopoietin-1 levels (ng/mL)(7 days from the date of randomization)
- Angiopoietin-2 levels (ng/mL)(7 days from the date of randomization)
- Lung vital capacity (L)(7 days from the date of randomization)
- Peak expiratory flow (L/s)(7 days from the date of randomization)
- S/F index (ratio)(7 days from the date of randomization)
- Incidence of adverse lung ultrasound findings (percentage)(7 days from the date of randomization)
- Six-minute walk test (6MWT) distance (meters)(10 days from the date of randomization)
- Surfactant protein SP-D plasma levels (ng/mL)(7 days from the date of randomization)
- sRAGE levels (pg/mL)(7 days from the date of randomization)
- endothelin-1 levels (pg/mL)(7 days from the date of randomization)
- Forced expiratory volume (L/s)(7 days from the date of randomization)
- VT-tidal volume (L)(10 days from the date of randomization)
- VE/VO2 - ventilatory equivalents for oxygen (ratio)(10 days from the date of randomization)
- VE/VСO2 - ventilatory equivalent for carbon dioxide(10 days from the date of randomization)
- Systolic blood pressure (SBP) levels (mmHg)(Every day from the date of randomization until day 7)
- Diastolic blood pressure (DBP) levels (mmHg)(Every day from the date of randomization until day 7)