The Study Will Evaluate the Use of Nintedanib in Slowing Lung Fibrosis in Patients With Pulmonary Infiltrates Related to COVID-19

Purpose

This is a collaborative study between Icahn School of Medicine at Mount Sinai and Boehringer Ingelheim Pharmaceuticals to determine the effect of Nintedanib on slowing the rate of lung fibrosis in patients who have been diagnosed with COVID-19, and have ongoing lung injury more than 4 weeks out from their diagnosis.

Conditions

  • Pulmonary Fibrosis
  • Interstitial Lung Disease
  • Respiratory Disease

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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 fibrosis found on CT scan (these may include 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 - Are 30 days from onset of initial SARS-CoV-2 symptoms - Forced Vital Capacity less than 80% predicted based on ATS/ERS criteria or DLCO<60% - Women of childbearing potential who agree to use of highly effective contraception during treatment and for three months following the last dose of nintedanib

Exclusion Criteria

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 - 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)

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
The study compares the effects of the active study drug, Nintedanib with an inactive substance (placebo). 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. 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. This way, the results of the study will not be favored one way or another. 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.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Nintedanib
150 mg po twice a day
  • Drug: Nintedanib
    150 mg PO twice a day, taken with food
Placebo Comparator
Placebo
placebo equivalent po twice a day
  • Drug: Placebo
    placebo equivalent given twice a day

Recruiting Locations

Icahn School of Medicine at Mount Sinai
New York, New York 10029
Contact:
Maria Padilla, MD
Maria.Padilla@mssm.edu

More Details

NCT ID
NCT04619680
Status
Recruiting
Sponsor
Icahn School of Medicine at Mount Sinai

Study Contact

ENDCOVI Study Team
646-992-7222
endcovi@mssm.edu

Detailed Description

The purpose of this study is to determine the efficacy of the study drug, Nintedanib, on slowing the rate of lung fibrosis in patients who are noted to have infiltrates, or ongoing lung injury, on chest x-ray/CT 4 weeks 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 studies in patients with post COVID 19 lung fibrosis. 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 at Mount Sinai, the study doctor will travel to the hospital room. - Undergo a HRCT (High-resolution computed tomography) scan of the chest within 14 days 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 blood drawn routinely while participating in this study (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. The main risks to participants are: 1. Common side effects include: nausea, vomiting, diarrhea, stomach discomfort 2. Loss of appetite and weight loss 3. Liver function abnormalities (blood work will be monitored periodic intervals at scheduled blood draws as listed above) 4. Slightly higher risk of bleeding 5. Slightly higher risk of blood clots that can form in the blood vessels that supply oxygen to vital organs such as the brain and heart Benefits from participation in this research include the possibility that Nintedanib may slow down/prevent progression of lung fibrosis. If the lungs can heal without fibrosis, this may result in fewer symptoms of shortness of breath, cough and need for added oxygen. Instead of participating in this research, subjects may choose to monitor their lung condition with their doctor or participate in another research study.