Corticosteroid Treatment for Post-COVID-19 Persistent Interstitial Lung Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- The rate of radiological, functional and quality of life improvement in prednisolone treatment for persistent interstitial lung disease following SARS-CoV-2.
研究概览
简要总结
Introduction: The new coronavirus (SARS-CoV-2) is a virus with an intense capacity for dissemination and high mortality rate. The main cause of death is viral pneumonia, characterized as organizing pneumonia that responds to treatment with corticosteroids. After 1 month of the acute phase, 25% of patients have complete recovery from lung lesions. However, lung lesions can evolve as persistent interstitial lung disease; it is possible that this persistent disease is also responsive to corticosteroid therapy. There are no controlled and randomized studies on any treatment and its effect on the natural history of this subacute or late manifestation of COVID-19.
Objective: To understand the effect of oral corticosteroid therapy in the treatment of persistent pulmonary manifestations (clinical and radiological) in patients who had moderate, severe, and critical forms of COVID-19. To understand the role of some risk factors in the development of this form of lung disease. To add information on the natural history of interstitial lung disease secondary to SARS-CoV-2 pulmonary infection.
Methodology: Randomized, double-blind, placebo-controlled study of patients who had COVID-19 viral pneumonia. Patients included after 12 weeks of COVID-19 diagnosis with RT-PCR or imaging tests that confirm the infection for inclusion in the protocol 100 patients with changes in high-resolution chest tomography and diffusion spirometry, will be divided into two groups, placebo and treatment; the treatment group will receive prednisolone at a dose of 0.5 mg/kg/day for 1 month and weaning in 30 days. Clinical, laboratory, functional, and imaging evaluations will be performed at the beginning, after 3 and 6 months of treatment and monthly telephone calls.
The evaluation will include a medical evaluation aimed at the cardiopulmonary assessment, arterial blood gas analysis at rest and after 6MWT; functional assessment with spirometry with measurements of FEV1, FVC, TLC, and DLCO; functional assessment during exercise with 6MWT; functionality questionnaires with SF-36, MMRC, and PCFS; and collection of laboratory tests including inflammatory markers - D-dimers, blood count, C-reactive protein and ESR, autoimmunity markers (ANA and RF), and collection of medical and laboratory history data during the acute infection to verify correlation with residual lung disease. Imaging evaluation will be performed with high-resolution chest tomography.
详细描述
The first case of the new coronavirus (SARS-CoV-2) was recorded in Wuhan, China.
A virus with a high capacity for dissemination, after 4 months, there were already 200,000 deaths caused by COVID-19 worldwide, and high incidence has a high lethality rate.
Up to 20% of affected patients require hospitalization and oxygen therapy, more than 5% of those affected will require intensive care and orotracheal intubation or critical cases, and 2 to 3% will die regardless of the treatment instituted.
The coronavirus infects human cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, a receptor present in cells of the lung, heart, kidney, and intestinal tissue (WU et al., 2020).
In lung tissue, it causes damage to the alveolar epithelium, which directly impacts the reduction of the gas exchange area, leading to a decrease in the diffusion capacity of oxygen and carbon dioxide. After the acute phase of the injury, the repair phase of the damaged tissue begins, and the gas exchange area improves, in most cases, enough for the patient to be removed from mechanical ventilation, but there will be extensive lung injury that is still in the recovery phase. At the time, lung tissue injury with characteristics of DAD was already evident, with the presence of multinucleated pneumocytes, which are secondary to the aggression of these cells and proliferation of intrabronchial fibro granular tissue (similar to organizing pneumonia or bronchiolitis obliterans - BOOP) (TSE et al., 2004), evidencing lymphocytic alveolitis, acute fibrinoid injury, and organizing pneumonia (REMMELINK et al., 2020).
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, Investigator)
盲法说明
Numbers 1 to 100 were randomly mixed up using a computer randomizer program. The first fifty were allocated as placebo and the last fifty as Treatment. Included patients received a number consecutively from 1 to 100. Only one researcher (EOV) knew to which group every number (patient) belonged, placebo or treatment. This researcher labeled medicine vials accordingly.
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
- •Over 18 years of age;
- •Diagnosis of COVID-19 by RT-PCR (Reverse transcription polymerase chain reaction), a test that detects the presence of viral antigen in nasal and oropharyngeal secretions or chest tomography typical of COVID-19 according to radiological standardization for COVID-19 cases (Machnicki, 2021);
- •Pulmonary involvement with persistent disease identified on high-resolution computed tomography of the chest;
- •Reduction in DLCO (percentage of predicted), with measurements less than or equal to 80%.
排除标准
- •Previous diagnosis of pulmonary embolism;
- •Previous and decompensated heart failure with electrocardiographic changes, chest X-ray with increased cardiac silhouette, and signs in the clinical examination suggestive of heart failure;
- •History of acute myocardial infarction in the last month or angina pectoris; Absolute contraindications to the use of corticosteroids or other comorbidities that prevent the use of corticosteroids such as uncontrolled diabetes, untreated glaucoma, current infections such as pneumonia or tuberculosis, and untreated psychiatric disorders;
- •Pregnancy and lactation;
- •Inability to perform stress tests such as walking tests and spirometry due to critically ill neuropathy or sequelae of stroke, among other limiting pathologies.
- •The patient will be informed of the risks related to corticosteroid treatment, and this information will be included in the consent form.
研究组 & 干预措施
Treatment
Treatment: corticosteroid therapy with prednisolone at a dose of half a milligram per kilogram per day, lasting 1 month, which will be gradually withdrawn with a 50% reduction in the dose every 7 days, up to a minimum dose of 5 mg for 7 days before stopping completely. The placebo group will receive tablets identical to prednisolone 20 mg for 1 month, and then the reduction will be done with placebo tablets identical to the 20 mg and 5 mg tablets.
The identification of the bottles and the preparation of the placebo tablets will be carried out by a compounding pharmacy that will identify the labels by codes, and a researcher on the team will learn the content related to each code (placebo or prednisolone). This researcher will not have access to the study care or procedures.
干预措施: Prednisolone (Drug)
Placebo
Patients who received placebo took a similar number of tablets for similar time span.
干预措施: Prednisolone (Drug)
结局指标
主要结局
The rate of radiological, functional and quality of life improvement in prednisolone treatment for persistent interstitial lung disease following SARS-CoV-2.
时间窗: 10 months
Rate of improvement, after treatment with prednisolone, of radiological, functional, and quality of life parameters in patients with persistent interstitial lung disease resulting from SARS-CoV-2 infection, in moderate, severe, and critical forms of COVID-19. Assessments were performed at 4, 7, and 10 months after diagnosis, .
次要结局
- The incidence of risk factors that may influence the severe outcome of COVID-19 lung disease.(In the first evaluation, 4 months after diagnosis.)
- Monitoring of post-COVID lung disease.(During recruitment and monitoring.)
研究者
Rosangela Villela Garcia
Medical doctor
University of Sao Paulo