Early Nintedanib Deployment in COVID-19 Interstitial Lung Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 121
- 试验地点
- 7
- 主要终点
- Change in Forced Vital Capacity (FVC)
研究概览
简要总结
This is a collaborative study between Icahn School of Medicine at Mount Sinai, Boehringer Ingelheim Pharmaceuticals and up to 9 other clinical centers across the US to determine the effect of nintedanib on slowing the rate of lung disease in patients who have been diagnosed with COVID-19, and have ongoing lung injury more than 30 days out from their diagnosis. Required one of the following after diagnosis with SARS-CoV-2: supplemental oxygen by nasal cannula, high flow oxygen, non invasive ventilation such as CPAP or BIPAP, or mechanical ventilation or a history of desaturation below 90%.
详细描述
The purpose of this study is to determine the efficacy of the study drug, nintedanib, on slowing the rate of lung disease in patients who are noted to have infiltrates, or ongoing lung injury, on chest x-ray/CT 30 days or longer from their initial symptoms. In addition, the study will also investigate patient reported outcomes using questionnaires, and the safety and tolerability of the study drug. Blood specimens will be collected to assess biomarkers and monitor drug safety.
The trial will be randomized 1:1 between nintedanib and placebo.
Nintedanib has been approved by the FDA for the treatment of chronic fibrosing ILD with a progressive phenotype, but has not been studied in patients with post COVID 19 lung disease.
Subjects participating in this study will:
- Attend in person visits to the study doctor's office on the date of enrollment, 15 days after enrollment, 45 days after enrollment, 90 days after enrollment, 135 days after enrollment, and 180 days after enrollment. If the participant is being enrolled in the study while hospitalized, the study doctor will travel to the hospital room. There will also be a follow-up phone call 30 days after finishing study drug.
- Undergo a HRCT (High-resolution computed tomography) scan of the chest within 6 weeks of enrollment, and then again at 180 days after enrollment.
- Have Pulmonary Function Tests within 14 days of enrollment, and then again 45, 90, 135 and 180 days after enrollment.
- Have a six-minute walk test at baseline, day 90 and day 180 after enrollment.
- Have blood drawn routinely while participating in this study (within 14 days of randomization, 15 days after starting medication, then again on day 45, 90, 135 and 180).
- Participants will not pay for physician visits, blood draws, breathing tests, CT scans or the medication for this study. Participants will receive a stipend to cover the transportation costs for your visits.
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
- Patients will be assigned to nintedanib or placebo by random chance in a 1:1 allocation. There is 50% chance to receive the study drug and a 50% chance to receive the placebo.
- Randomization will be stratified by site and subgroup (fibrotic and non-fibrotic) to ensure treatment balance. I.e., within the fibrotic subgroup, the randomization will ensure 50% are assigned to the nintedanib arm and 50% are assigned to the placebo arm. Similarly, treatment balance within the non-fibrotic subgroup will be ensured.
- The study will be double blinded. No one (including the patient or the study team) will know who is receiving the study drug or the placebo. If it becomes urgently necessary for a patient's care, the study doctor will be able to find out whether the patient is taking the placebo or the study drug, nintedanib.
- Patients will be told whether they received the study drug, nintedanib, or the placebo once the study is finished.
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
- •Willing and able to provide written informed consent
- •Subjects Age ≥ 18
- •Initial SARS-CoV-2 infection confirmed by PCR test or positive serologies
- •Have findings consistent with interstitial lung disease found on CT scan (these may include ground glass opacities, reticulations, traction bronchiectasis, septal thickening, and early honeycombing)
- •Required one of the following after diagnosis with SARS-CoV-2: supplemental oxygen by nasal cannula, high flow oxygen, non invasive ventilation such as CPAP or BIPAP, or mechanical ventilation or a history of desaturation below 90%
- •Are at least 30 days from onset of initial SARS-CoV-2 symptoms
- •Forced Vital Capacity less than or equal to 90% predicted based on ATS/ERS criteria or DLCO less than or equal to 70%
- •Women of childbearing potential who agree to use of highly effective contraception during treatment and for three months following the last dose of nintedanib
排除标准
- •Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of the Screening Visit (prior to randomization):
- •Co-administration of other investigational agents against COVID-19
- •Active SARS-CoV-2 infection based on clinical judgment
- •Currently Pregnant or Breast Feeding
- •Current Use of Prednisone or equivalent > 10 mg/daily or immunosuppressive therapy or disease modifying agents
- •Use of full dose anticoagulation therapy or high dose anti platelet drug therapy at screening (at the discretion of the investigator, anticoagulation therapy may be added if clinically indicated)
- •History of myocardial infarction within past 90 days
- •Life threatening bleed
- •Hemodynamic instability or shock
- •Superimposed pulmonary bacterial infection
- •Pre-existing interstitial lung disease
- •Active Hep A/B/C hepatitis as measured with PCR for viral load and/or serologies
- •Pre-existing liver disease: Including Abnormal Laboratory Liver Function: Childs Pugh B/C, AST/ALT > 3 times the upper limit of normal (ULN). If Child Pugh A, can participate on nintedanib 100 mg by mouth twice daily.
- •Subjects with a Creatinine clearance <30 ml/min or currently on hemodialysis
- •Inability to tolerate orally administered medication (medication must be taken with meals)
- •Patients who are in the intensive care unit (ICU) or in the step-down unit on invasive or non-invasive mechanical ventilation, ECMO, or high flow nasal cannula oxygen, will not be included.
- •Any condition that in the opinion of the Investigator, constitute a risk or a contraindication for the participation of the patient into the study or that could interfere with the study objectives, conduct or evaluation.
- •Patients with known hypersensitivity to nintedanib, peanut, soy, or to any of the excipients.
研究组 & 干预措施
Nintedanib
150 mg PO twice a day, taken with food, (or, for Child-Pugh A patients, 100 mg by mouth twice daily).
干预措施: Nintedanib (Drug)
Placebo
placebo equivalent 150mg PO twice a day, taken with food food (or, for Child-Pugh A patients, 100 mg by mouth twice daily).
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Forced Vital Capacity (FVC)
时间窗: Baseline and 180 days
Change in Forced Vital Capacity (FVC) at 180 days as compared to baseline. Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from your lungs after taking the deepest breath possible, as measured by spirometry.
次要结局
- St. George's Respiratory Questionnaire (SGRQ)(Day 180)
- King's Brief Interstitial Lung Disease Questionnaire(KBILD)(Day 180)
- Number of deaths due to respiratory cause(within 90-180 days)
- King's Brief Interstitial Lung Disease Questionnaire (KBILD)(Day 90)
- Short Form (SF) 36 Health Survey(Day 180)
- Chest CT visual score(180 days)
- Number of participants with Increase in liver transaminases (AST and ALT) > 3 times the upper limit of normal(day 180)
- Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)(Baseline and Day 180)
- Leicester Cough Questionnaire (LCQ)(Day 180)
- Number of participants with Thrombotic events(day 180)
- Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F)(Day 180)
- Hospital Anxiety and Depression Scale (HADS)(Day 180)
- Number of participants with GI events(day 180)
- Change in Forced Vital Capacity (FVC)(Baseline and Day 90)
- Number of deaths due to any cause(within 90-180 days)
- Number of participants with 10% weight loss over 90 days(day 180)
- Change in 6 minute walk test(Baseline and day 180)
研究者
Maria L Padilla
Professor
Icahn School of Medicine at Mount Sinai