The Effectiveness of Adding Multiple Intermittent High-dose Inhalations of Nitric Oxide to Standard Antibacterial Therapy in the Treatment of Pneumonia
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Pneumonia resolution time (days)
研究概览
简要总结
This is a multicenter, prospective randomized controlled trial. At least 2 but no more than 5 centers are expected to participate in the study.
The primary objective is to test the hypothesis that the addition of high-dose inhaled nitric oxide therapy to standard treatment has a positive effect on the clinical course of pneumonia and the structure and function of cardiopulmonary system.
Number of participants: 200, including the subproject NO-PNEUMONIA-CAP - 100 CAP participants, the subproject NO-PNEUMONIA-NP - 100 NP participants.
Number of groups: 4 Inhalation of iNO at a dose of 200 ppm for 30 minutes under the control of methemoglobin level (no more than 5%) three times a day if the patient is allocated to the main group. The general course of iNO therapy will last until the pneumonia resolves, but no more than 7 days. Recording of vital signs and safety assessment will be carried out immediately before the initiation of NO therapy and every 15 minutes after its start (pulse, blood pressure, respiratory rate, SpO2, temperature, MetHb level).
详细描述
Principal investigator: T.P. Kalashnikova, MD, PhD. Sub-investigators: N.O.Kamenshchikov, MD, PhD, I.V. Kravchenko, MD, Yu.A. Arsenyeva, MD, Yu.K. Podoksenov, MD, PhD, DMedSci, M.S. Kozulin, MD, M.B. Gorchakova, MD, B.N. Kozlov, MD, PhD, DMedSci, A.A. Boshchenko, MD, PhD, DMedSci.
RESEARCH RELEVANCE Pneumonia remains one of the most common infectious respiratory diseases worldwide. Community-acquired pneumonia (CAP) is defined as pneumonia that is acquired outside the hospital or diagnosed in the first 48 hours from hospitalization. Nosocomial pneumonia (NP) is diagnosed in individuals with symptoms of the disease that develop 48 hours or more after the patient's hospitalization. The most common causative agents of CAP are S. pneumoniae, M. pneumoniae, C. pneumoniae, H. influenza, as well as viruses and microbial associations. In recent years, there has been an increase in the resistance of CAP pathogens to antibiotics of the group of aminopenicillins, cephalosporins, and macrolides.
In the etiological structure of NP, the leading role belongs to gram-negative microorganisms. The main pathogens are representatives of Enterobacteriaceae (including Klebsiella pneumoniae and E.coli), Acinetobacter baumannii, Pseudomonas aeruginosa, characterized by a high level of resistance to antimicrobial drugs.
Considering the high prevalence of pneumonia, the continuous increase in the resistance of microorganisms to antimicrobial agents, the high mortality rate from adverse reactions caused by multidrug-resistant bacteria, the lack of development of new drugs with proven antibacterial effectiveness, and the high economic costs of treatment, it is urgent to search for alternative ways to increase efficiency in the treatment of pneumonia . From this point of view, the addition of inhaled high doses of nitric oxide (iNO) to standard antibacterial therapy seems promising.
The positive results of using NO have been proven in the treatment of patients with pulmonary hypertension, chronic obstructive pulmonary disease, acute respiratory distress syndrome (ARDS), and in the treatment of wound processes. There is a cardioprotective and nephroprotective effect of this molecule that has been described. In recent years, data have appeared on the successful use of iNO in the treatment of viral pneumonia, in particular in pneumonia caused by the Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV2). High concentrations of nitric oxide cause cytotoxic, antibacterial, antiviral, and antifungal effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •An established diagnosis of Nosocomial Pneumonia (NP) after cardiac surgery under cardiopulmonary bypass (CPB) or hospitalization for Community-acquired pneumonia (CAP).
- •Spontaneous breathing.
- •Age > 18 years.
- •Signed informed consent.
- •Negative result of immunochromatographic Severe acute respiratory syndrome-related coronavirus 2 rapid antigen test on the day of diagnosis of pneumonia.
- •Diagnostic criteria for NP The diagnosis of NP is considered established when the number of points on the
- •Clinical Pulmonary Infection Score (CPIS) is greater than 6:
- •Diagnostic criteria for CAP:
- •Radiologically confirmed focal pulmonary opacity and at least 2 clinical symptoms and signs of the following:
- •acute fever at the onset of the disease (t° > 38.0°C);
- •cough with sputum;
- •physical signs (crepitus/fine rales, bronchial breathing, shortening of percussion sound);
- •leukocytosis > 10x109/l and/or left shift (> 10%)
排除标准
- •Diagnosed infectious process of another localization (surgical site infection (SSI), acute and chronic urinary tract infection (active), catheter-related bloodstream infection, peritonitis, infective endocarditis etc.).
- •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 the development of pneumonia.
- •History of malignancy or other irreversible diseases/conditions with a life expectancy of less than 1 year.
- •Presence of HIV infection
研究组 & 干预措施
Control group with nosocomial pneumonia
Standard antibacterial therapy + medical air without Nitric Oxide 3 times a day for 30 minutes until the pneumonia resolves, but no more than 7 days.
干预措施: Sham treatment (Drug)
Main group with nosocomial pneumonia
Standard antibacterial therapy + Nitric Oxide 200 ppm 3 times a day for 30 minutes under the control of methemoglobin level (no more than 5%). The general course of Nitric Oxide therapy will last until the pneumonia resolves, but no more than 7 days.
干预措施: 200 ppm Nitric Oxide (Drug)
Main group with community acquired pneumonia
Standard antibacterial therapy + Nitric Oxide 200 ppm 3 times a day for 30 minutes under the control of methemoglobin level (no more than 5%). The general course of Nitric Oxide therapy will last until the pneumonia resolves, but no more than 7 days.
干预措施: 200 ppm Nitric Oxide (Drug)
Control group with community acquired pneumonia
Standard antibacterial therapy + medical air without Nitric Oxide 3 times a day for 30 minutes until the pneumonia resolves, but no more than 7 days.
干预措施: Sham treatment (Drug)
结局指标
主要结局
Pneumonia resolution time (days)
时间窗: 30 days from the date of randomization
Pneumonia resolution time is assessed as number of days from the date of randomization till pneumonia resolution.
次要结局
- Fever higher than 37˚C (days)(30 days from the date of randomization)
- Right atrial volume index (RAVI) (mL/m2)(72 hours from the start of therapy)
- Right ventricular volume index (mL/m2)(72 hours from the start of therapy)
- Pneumonia resolution-associated right atrial volume index (RAVI) (mL/m2)(30 days from the date of randomization)
- Pneumonia resolution-associated right ventricular volume index (mL/m2)(30 days from the date of randomization)
- Increased peak tricuspid regurgitation velocity (percentage)(30 days from the date of randomization)
- Total leukocyte counts (10*9/L)(72 hours from the start of therapy)
- Immature cell counts (percentage)(72 hours from the start of therapy)
- Procalcitonin (PCT) level (ng/mL)(72 hours from the start of therapy)
- Pneumonia resolution-associated change in procalcitonin (PCT) level (ng/mL)(30 days from the date of randomization)
- Respiratory support time (days)(30 days from the date of randomization)
- Pneumonia resolution-associated change in total leukocyte counts (10*9/L)(30 days from the date of randomization)
- Pneumonia resolution-associated change in immature cell counts (percentage)(30 days from the date of randomization)
- C-reactive protein (CRP) level(72 hours from the start of therapy)
- Pneumonia resolution-associated change in C-reactive protein level (mg/L)(30 days from the date of randomization)
- Incidence of sepsis (percentage)(30 days from the date of randomization)
- Incidence of septic shock (percentage)(30 days from the date of randomization)
- Incidence of oxygen saturation decrease (percentage)(30 days from the date of randomization)
- Frequency of changing antibacterial treatment regimens (times)(30 days from the date of randomization)
- Incidence of adverse computer tomography (CT) findings (percentage)(72 hours from the start of therapy)
- Six-minute walk test (6MWT) distance (meters)(30 days from the date of randomization)
- Lung vital capacity (L)(30 days from the date of randomization)
- Forced vital capacity (L)(30 days from the date of randomization)
- Forced expiratory volume (L/s)(30 days from the date of randomization)
- Peak expiratory flow (L/s)(30 days from the date of randomization)
- Quality of life (score)(30 days from the date of randomization)
- Mortality caused by pneumonia or its complications (percentage)(30 days from the date of randomization)
- Increased peak tricuspid regurgitation velocity (percentage)(72 hours from the start of therapy)
- Quality of life (score)(72 hours from the date of randomization)
研究者
Tatiana P. Kalashnikova
MD, PhD, senior researcher of Laboratory
Tomsk National Research Medical Center of the Russian Academy of Sciences