Phase-II Randomized Clinical Trial to Evaluate the Effect of Pirfenidone Compared to Placebo in Post-COVID19 Pulmonary Fibrosis
试验速览
- 阶段
- 2 期
- 入组人数
- 148
- 试验地点
- 8
- 主要终点
- To investigate the effect of pirfenidone on fibrotic signs induced by COVID19 infection
研究概览
简要总结
Study population: Patients with fibrotic lung sequelae after recovery from acute phase of severe COVID19 pneumonia Objectives: To evaluate the effect of pirfenidone administered for 24 weeks in patients who have pulmonary fibrotic changes after suffering severe COVID19 pneumonia, analysed by
- % change in forced vital capacity (FVC)
- % fibrosis in high resolution computed tomography (HRCT) of the lung
详细描述
Has been designed a clinical trial with an experimental and a control arm, with 2 experimental subjects per control (2:1), we will have to study 98 experimental subjects and 50 control subjects, in total 148 patients. Randomization will be performed using a centralized electronic system (IVRS) with 2: 1 randomized concealed assignment. This randomization will be done by permuted blocks.
The study population will be patients with fibrosing lung sequelae after recovery from severe COVID19 pneumonia.
This is a double-blind, masked, placebo-controlled clinical trial: the patient and the investigator are unaware of the assigned treatment the patient receives.
Patients will follow a total of 5 clinic visits; V0 (screening, -1 days - +42 days from signing the Informed Consent), V1 (randomization), V2 (week 12), V3 (week 24 or end of treatment), V4 (week 28 or follow-up).
Visits Plan
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, Investigator)
盲法说明
doble blinded, IVRSystem
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
- •Signed Informed Consent Form
- •Ability to comply with the study protocol in the opinion of the Investigator
- •Confirmation of SARS-COV2 infection in previous weeks (Confirmation of negativity or no activity of SARS-COV2 before randomization using the usual tests performed in the hospital), which induced severe pneumonia and ARDS, with subsequent torpid recovery and/or incipient clinical-radiological signs of pulmonary fibrosis.
- •HRCT with fibrotic radiological changes of at least 5% after recovery from the acute process (HRCT chest during the screening period, performed minimum after 1 month of the acute phase and maximum 90 days after hospital discharge)
- •Be able to understand the information given and sign the informed consent
- •For women or men of childbearing age who are not sterile, a commitment to use non-hormonal contraception during the 24-week treatment period will be required.
排除标准
- •Use of systemic steroids (oral or intravenous) at doses greater than 15 mg/day one month prior to randomisation.
- •Severe or moderate myopathy that may associate a decrease of FVC.
- •Severe or life-limiting chronic disease prior to COVID19 infection, including severe asthma, cancer, clinical dementia, IPF, or uncontrolled ischemic cardiomyopathy.
- •Treatment with pirfenidone or nintedanib prior to Covid19
- •Concomitant treatment with significant interactions with pirfenidone (such as fluvoxamine).
- •Participation in any other investigational trial throughout the study
- •Active smoking.
- •Relevant blood alterations in the analysis made during the screening period:
- •Total bilirubin > 2 ULN
- •AST/SGOT or ALT/SGPT > 2.5 ULN
- •Alkaline phosphatase >3.0 ULN
- •Creatinine Clearance <40 mL/min, calculated by the Cockcroft-Gault formula
- •Pregnancy or lactation
- •Concomitant treatments that can cause severe digestive problems.
- •Gastric surgery in the last 3 months or similar procedures that may increase gastric intolerance.
- •Inability to complete required visits.
- •Previous intolerance or allergy to pirfenidone or hypersensitivity to any of its excipients.
- •History of angioedema
研究组 & 干预措施
Placebo
No anti-fibrotic treatment. Patients in placebo and treatment arm may be on corticosteroid treatment
干预措施: Placebo (Drug)
Treatment
Pirfenidone
干预措施: Pirfenidone (Drug)
结局指标
主要结局
To investigate the effect of pirfenidone on fibrotic signs induced by COVID19 infection
时间窗: 24 weeks
To investigate the effect of pirfenidone administered for 24 weeks measuring the number of patients who have pulmonary fibrotic changes from baseline after suffering severe COVID19 pneumonia, analysed by * Change From Baseline in % in forced vital capacity (FVC) * Change From Baseline % fibrosis in high resolution computed tomography (HRCT) of the lung
次要结局
- Maintenance of stability or functional improvement FVC(24 weeks)
- Lung transplantation(24 weeks)
- Decreased oxygen requirement for physical activity(24 weeks)
- Improved exercise capacity (> 50 meter improvement or less decrease in% oxygen saturation) in the TM6m(24 weeks)
- Hospitalizations (general and due to respiratory problems)(24 weeks)
- Death(24 weeks)
- Visits to the Emergency or Day Hospital for respiratory causes(24 weeks)
研究者
Maria Molina
Coordinating Investigator
Institut d'Investigació Biomèdica de Bellvitge