Single-center, Prospective, Open-label, Comparator Study, Blind for Central Accessor to Access the Efficacy, Safety, and Tolerability of Inhalations of Low-doses of Melphalan in Patients With Pneumonia With Confirmed or Suspected COVID-19
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- The changes of COVID Ordinal Outcomes Scale
研究概览
简要总结
This single-center, prospective, open-label, comparator study, blind for central accessor evaluates the efficacy, safety of inhalations of low-doses of melphalan in patients with pneumonia with confirmed or suspected COVID-19. All patients will receive 0,1 mg of melphalan in 7-10 daily inhalations 1 time per day.
详细描述
It was previously shown that in ultra-low (more than 100 times lower than conventional therapeutic) doses inhalations of alkylating drug (melphalan) are effective in severe steroid-resistant bronchial asthma, a form of the disease often characterised by neutrophilic type of inflammation. The exacerbation frequency reduced after the treatment, steroid-sparing effect was shown, morphological signs of bronchial epithelial regeneration were revealed and quality of life of asthmatic patients, treated with ultra-low doses of melphalan, improved. In preclinical studies and studies with volunteers, it was found that inhalations of ultra-low doses of melphalan do not have cytotoxic properties, but have local and systemic anti-inflammatory effects and decrease the activation of lymphocytes due to blockade of heavy β-chain of the interleukin (IL)-2 surface receptor. In addition, in ultra-low concentrations, alkylating agents are able to disrupt the cell signalling through the receptor for tumor necrosis factor (TNF), thereby exerting a protective effect from the cytotoxic activity of TNF-α, which leads to the anti-inflammatory response.
Taking into account, that severe cases of COVID are characterised with hyperergic inflammatory response (and in some cases even with the development of "cytokine storm") it can be assumed that the inhalation use of low-doses of melphalan due to its anti-inflammatory properties can be effective treatment for patients with COVID-associated pneumonia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
An independent central blinded assessor will be blinded to study treatment and will review the clinical response assessments. In case of a discrepancy with the Investigator's assignment of clinical response, the adjudication committee's assessment will prevail.
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
- •Age ≥18 years
- •A patient must have confirmed the diagnosis of bi-lateral moderate / severe pneumonia ( viral or viral-bacterial with confirmed of suspected COVID-19).
- •Presence new infiltrates or increase already available infiltrates of pulmonary infiltrates on lung CT within 48 hours before baseline.
- •A patient has as minimum one of the following symptoms:
- •fever >38 degrees Celsius, cough, dyspnea, SaO2 (arterial oxygen saturation) <95% (with room air)
排除标准
- •Informed consent is withdrawn by the patient.
- •The patient doesn't follow the instructions of the research staff regarding the requirements of the research protocol.
- •Unable to contact the patient.
- •The researcher believes that participation in the study is not in the interests of the patient and / or further participation in the study is unsafe for the patient's health.
- •There is a violation of the criteria for inclusion and / or non-inclusion in the study.
- •The patient has developed an adverse event, which, according to the researcher, makes further participation in the study unsafe for the patient.
- •The licensing authority or ethics committee, for any reason, decides to discontinue the entire study or close this research center.
- •A female patient becomes pregnant, is planning a pregnancy, or is breastfeeding while participating in this study.
研究组 & 干预措施
Melphalan inhalations
Inhalations with Melphalan 0,1 mg dissolved in 2 ml sodium chloride (NaCl) 0,9% 1 per day for 7-10 consequent days
干预措施: Melphalan (Drug)
Standard of care group
Patients assigned to the standard of care group will not receive any additional therapy.
干预措施: Standard of care (Other)
结局指标
主要结局
The changes of COVID Ordinal Outcomes Scale
时间窗: baseline vs Day 14, day 28
The number of patients with the clinical improvement is defined as an improvement of two points (from the status at baseline) on an ordinal scale of clinical improvement on day 28 or discharge from hospital ( whatever occurs earlier) 1. Death 2. Hospitalized with Invasive mechanical ventilation plus additional organ support - ECMO / pressors / RRT 3. Hospitalized with intubation and mechanical ventilation 4. Hospitalized on non-invasive ventilation or high flow oxygen. 5. Hospitalized on a mask or nasal prongs. 6. Hospitalized no oxygen therapy. 7. Ambulatory, with limitation of activities. 8. Ambulatory, no limitation of activities. I. No clinical or virological evidence of infection.
Percentage of the patients with Clinical Recovery
时间窗: baseline vs day 7, day 14, day 28
Percentage of the patients with clinical recovery which is defined as a normalisation of fever, respiratory rate, and oxygen saturation, and improvement of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first. Normalization and improvement criteria: * Fever - \<37°C, * Respiratory rate - ≤24/minute on room air, * Oxygen saturation - \>94% on room air, * Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.
The changes of the Borg's scale
时间窗: Baseline vs day 7, day 14, day 28
The evaluation of changes in modified Borg dyspnea scale. From 0 to 10 units.A lower score means a better clinical result (0 is the absence of dyspnea, and 10 - is maximal dyspnea). Minimal clinically important difference is 1 unit.
次要结局
- CRP level(baseline, day 7, Day 14, Day 28)
- Lymphocyte count(baseline, day 7, Day 14, Day 28)
- D-dimer(baseline, day 7, Day 14, Day 28)
- IL-6(baseline, day 7, Day 14, Day 28)
- Percentage of patients without artificial lung ventilation(baseline, day 7, Day 14, Day 28)
研究者
Kirill Zykov
Deputy director for Science and Innovations
Federal State Budgetary Institution, Pulmonology Scientific Research Institute