Treatment With Pirfenidone for COVID-19 Related Severe ARDS An Open Label Pilot Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Severe adverse events (SAEs) rate
研究概览
简要总结
A randomized, open label, two arm, pilot trial of Pirfenidone 2,403 mg administered per nasogastric tube or orally as 801mg TID for 4 weeks in addition to Standard of Care (SoC), compared to SoC alone, in a population of COVID-19 induced severe ARDS. Patients will be randomized according to 1:1 ratio to one of the trial arms: Pirfenidone (intervention arm) or SoC (control arm).
详细描述
The objective of the trial is to evaluate the safety and efficacy of treatment with Pirfenidone vs SoC in COVID-19 induced severe Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation.
Following initial diagnosis of COVID-19, severe ARDS patient will be admitted to a dedicated intensive care unit (ICU) at Soroka University Medical Center (Day 0). Upon admission, patients will be randomized according to 1:1 ratio to one of the trial arms and receive either Pirfenidone 2,403mg administered through nasogastric tube as 801mg TID (intervention arm) plus SoC or only SoC treatment (control arm).
Patients' vital signs (temperature, blood pressure, pulse rate per minute, breath rate per minute, oxygen saturation) urine output, ventilation settings, and respiratory parameters will be monitored according to SoC. Symptom will be captured daily from patients as well as adverse events (AEs) assessment and recording of the need for any supportive care during the period of ICU admission.
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
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women between the ages 18-80 years
- •Diagnosis of COVID19 with severe ARDS (PaO2/FIO2 <150mmHg)
- •Admission to the ICU and in need of mechanical ventilation
- •Able to give informed consent according to local regulations. If the patient is unable to give written informed consent, the form will be read to them and their verbal consent will be documented. If the patient is sedated, an impartial ICU physician will approve eligibility.
排除标准
- •Previous use of nintedanib or pirfenidone
- •Administration of fluvoxamine 7 days prior to admission to ICU
- •Severe hepatic impairment (liver enzymes and bilirubin>2 of normal upper limit, at day 0) or end stage liver disease
- •Severe renal impairment (CrCl <30 ml/min) or end stage renal disease requiring dialysis
- •Pregnancy
- •Participation in any other clinical trial 30 days prior to enrollment
研究组 & 干预措施
Standard of Care - Control
Standard of care (Soc) according to current guidelines and the discretion of treating physician.
干预措施: Standard of care (Other)
Pirfenidone Treatment
In addition to SoC, Pirfenidone 2,403 mg administered orally or per nasogastric tube as 801mg TID, for 4 weeks.
Pirfenidone dose will be 2,403mg daily, from day one of admission to the ICU, titrated over 3 days:
Day 1 - 801mg x 1/d (801mg) Day 2 - 801mg x 2/d (1,602 mg) Day 3 - 801mg x 3/d (2,403 mg) Feeding and medication delivery will be upon the discretion of the treating physician according to tolerability. Powdered 801mg tablets will be administered through the nasogastric tube: Each tablet will be crushed and dissolved in 20cc of water. The nasogastric tube will be flushed afterwards to avoid obstruction..
If the patient is able to swallow and the nasogastric tube is removed, pirfenidone will continue to be delivered orally.
干预措施: Pirfenidone (Drug)
结局指标
主要结局
Severe adverse events (SAEs) rate
时间窗: Through study completion, an average of 1 year
Number of SAEs divided to number of patients
Ventilation free days to day 28 (VFD28)
时间窗: Up to 28 days from admission to ICU
Measured in number of days
次要结局
- Tidal Volume(Through study completion, an average of 1 year)
- Positive End Expiratory Pressure (PEEP)(Through study completion, an average of 1 year)
- Driving Pressure(Through study completion, an average of 1 year)
- Quality of life questionnaire(on admission and 6 months after discharge)
- Mortality(Through study completion, an average of 1 year)
- ICU length of stay(Through study completion, an average of 1 year)
- Lung compliance(Through study completion, an average of 1 year)
- Vital Capacity (VC)(On admission (if possible) and 6 months after discharge)
- Forced Vital Capacity (FVC)(On admission (if possible) and 6 months after discharge)
- Forced Expiratory Volume at first second (FEV1)(On admission (if possible) and 6 months after discharge)
- Diffusing Capacity for Carbon Monoxide (DLCO)(On admission (if possible) and 6 months after discharge)
- 6 minutes walking test(6 months after discharge from hospital)
研究者
Yasmeen Abu Fraiha
Internal Medicine resident, MD
Soroka University Medical Center