Pulmonary FibrosisPhase 4ENDCOV-INCT04619680
The Study of the Use of Nintedanib in Slowing Lung Disease in Patients With Fibrotic or Non-Fibrotic Interstitial Lung Disease Related to COVID-19
A Phase 4 study testing Nintedanib in people with Pulmonary Fibrosis and Interstitial Lung Disease, run by Icahn School of Medicine at Mount Sinai at 7 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Fibrosis, Interstitial Lung Disease, Respiratory Disease
- What is being tested?
- Nintedanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 7 sitesUnited States
- Study dates
- 18 Nov 2020to 2 Mar 2024
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Emory Healthcare Network
Atlanta, Georgia, 30322
The Johns Hopkins Hospital
Baltimore, Maryland, 21287
Baylor University Medical Center Dallas
Dallas, Texas, 75246
Baylor College of Medicine
Houston, Texas, 77030
Mount Sinai Beth Israel
New York, New York, 10003
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
University of Utah
Salt Lake City, Utah, 84108
About this study
Official title: Early Nintedanib Deployment in COVID-19 Interstitial Lung Disease
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%.
Read the detailed description
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.
The main risks to participants are:
- Common side effects include: nausea, vomiting, diarrhea, stomach discomfort
- Loss of appetite and weight loss
- Liver function abnormalities (blood work will be monitored periodic intervals at scheduled blood draws as listed above)
- Slightly higher risk of bleeding
- 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
- Kidney disease resulting in protein/and or albumin being lost through urine
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.
- Being tested
- Nintedanib, Placebo
- Keywords
- COVID-19, Infiltrates, SARS CoV-2, lung, scarring, fibrosis
- Medical subject headings
- Pulmonary Fibrosis, Lung Diseases, Interstitial, Respiration Disorders, COVID-19, Cicatrix, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NintedanibDrug
150 mg PO twice a day, taken with food food (or, for Child-Pugh A patients, 100 mg by mouth twice daily).
PlaceboDrug
placebo 150 mg equivalent twice a day, taken with food food (or, for Child-Pugh A patients, 100 mg by mouth twice daily).
| Study group | Role | What they receive |
|---|---|---|
| Nintedanib | Experimental | 150 mg PO twice a day, taken with food, (or, for Child-Pugh A patients, 100 mg by mouth twice daily). Receives: Drug: Nintedanib |
| Placebo | Placebo comparator | placebo equivalent 150mg PO twice a day, taken with food food (or, for Child-Pugh A patients, 100 mg by mouth twice daily). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Forced Vital Capacity (FVC)
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.
Measured: Baseline and 180 days
Secondary outcomes (17)
Number of Deaths Due to Respiratory Cause
Death within 90 days and 180 days from enrollment due to a respiratory cause
Measured: within 90-180 days
Number of Participants With Change in Chest CT Visual Score
Quantitative Change in chest CT visual score graded by blinded chest radiologists. Data driven texture analysis (DTA) is a patented deep learning method to quantify lung fibrosis. DTA score is reported in percentage ranging from 0% to 100%. A minimally clinical important difference when comparing CT scans from the same subject is 4%. A higher percentage suggests worsening lung injury.
Measured: 180 days
Chest CT Visual Score
Quantitative Change in chest CT visual score graded by blinded chest radiologists. Data driven texture analysis (DTA) is a patented deep learning method to quantify lung fibrosis. DTA score is reported in percentage ranging from 0% to 100%. A minimally clinical important difference when comparing CT scans from the same subject is 4%. A higher percentage suggests worsening lung injury.
Measured: 180 days
Change in St. George's Respiratory Questionnaire (SGRQ)
The Saint George's Respiratory Questionnaire (SGRQ) is a self-reported disease-specific, health-related quality of life (QOL) questionnaire. 50-item instrument. Scores range from 0 to 100, with higher scores indicating more limitations. Change in SGRQ at Day 180 as compared to baseline
Measured: Baseline and Day 180
Change in King's Brief Interstitial Lung Disease Questionnaire (KBILD)
The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a self-administered, ILD-specific measure of health-related quality of life, comprising 15 items with three domains (Psychological (KBILD-P), Breathlessness and activities (KBILD-B), and Chest symptoms (KBILD-C)) combined in a total score (KBILD-T). The KBILD domain and total score ranges are 0-100; 100 represents best health status. Change in KBILD score at Day 180 as compared to baseline.
Measured: Baseline and Day 180
Change in Leicester Cough Questionnaire (LCQ)
The LCQ is a 19 item questionnaire that assesses cough-related QOL. It has 3 domains (physical, psychological and social). The domain scores range from 1-7 and total score range is 3-21 with a higher score indicating a better quality of life. Change in LCQ at Day 180 as compared to baseline
Measured: Baseline and Day 180
Short Form (SF) 36 Health Survey
The (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status in 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Raw scale scores range from 0 - 100, with higher scores indicating less disability. Scores are averaged and converted to T scores to two composites: Physical Health and Mental Health. T score is a conversion of scores to a standardized scale with a mean of 50 and a standard deviation of 10. A higher score indicates better health.
Measured: Day 180
Change in Hospital Anxiety and Depression Scale (HADS)
Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4-point response 0 - 3.
Scores for each subscale from 0 (normal) to 21 (severe symptoms). Scores for the entire scale is 0 to 42, with higher score indicating more symptoms for anxiety or depression.
Change in HADS at Day 180 as compared to baseline.
Measured: Baseline and Day 180
Number of Participants With Increase in Liver Transaminases (AST and ALT) > 3 Times the Upper Limit of Normal
Number of participants with Increase in liver transaminases
Measured: day 90 and 180
Number of Participants With Thrombotic Events
Number of participants with Thrombotic events: venous or arterial thrombosis
Measured: day 180
Number of Participants With 10% Weight Loss at 90 Days and 180 Days
Number of participants with 10% weight loss
Measured: Day 90 and 180
Number of Participants With GI Events
Number of participants with Nausea/emesis/diarrhea not responsive to anti-emetics and anti-motility agents
Measured: day 180
Change in 6 Minute Walk Test (6MWT)
The distance covered over a time of 6 minutes at day 180 as compared to baseline.
Measured: Baseline and day 180
Change in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F)
The FACIT-F is a 40-item measure that assesses self-reported fatigue and its impact upon daily activities and function. Questions are scored on a 5-point Likert scale. The total score range is from 0-52, with higher score indicating lower fatigue level. Change in FACIT-F at Day 180 as compared to baseline.
Measured: Baseline and Day 180
Change in Forced Vital Capacity (FVC)
Change in Forced Vital Capacity (FVC) at 90 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.
Measured: Baseline and Day 90
Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) at 180 days as compared to baseline. Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) measures the transfer of carbon monoxide from alveolar gas to hemoglobin in pulmonary capillary blood. DLCO is measured by having the patient fully inhale a low concentration of carbon monoxide and an inert tracer gas.
The results of a lung diffusion test are given in a percentage of what is the expected DLCO to be (predicted value).
Normal DLCO: Between 75% and 140% of the predicted value. Mildly reduced DLCO: 60% to 75% or the lower limit of normal (LLN) predicted value.
Severely reduced DLCO: Less than 40% of the predicted value.
Measured: Baseline and Day 180
Number of Deaths Due to Any Cause
Number of deaths within 90 days and 180 days from enrollment due to a any cause
Measured: within 90-180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2020
- Study start18 Nov 2020
- Primary completion1 Feb 2024
- Study completion2 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary FibrosisStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Principal investigator, Maria L Padilla, Icahn School of Medicine at Mount Sinai
- Investigators
- Maria Padilla, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04619680
- Sponsor's protocol ID
- GCO 20-2147
- Acronym
- ENDCOV-I
- Status last verified
- Apr 2025
- First submitted
- 5 Nov 2020
- Last updated
- 30 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after deidentification.
Publications
Santibanez V, Mathur A, Zatakia J, Ng N, Cohen M, Bagiella E, Brown SA, Rosas IO, Patel NM, Olson A, Li P, Padilla M. Early nintedanib deployment in COVID-19 interstitial lung disease (ENDCOV-I): study protocol of a randomised, double-blind, placebo-controlled trial. BMJ Open Respir Res. 2025 Apr 10;12(1):e002323. doi: 10.1136/bmjresp-2024-002323.
PubMed 40216412