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

NCT04619680 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: GCO 20-2147
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 7

Brief 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 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%.

Conditions

Pulmonary Fibrosis; Interstitial Lung Disease; Respiratory Disease

Keywords

COVID-19; Infiltrates; SARS CoV-2; lung; scarring; fibrosis

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and 180 days

Secondary Outcomes (17)

• Number of Deaths Due to Respiratory Cause

  within 90-180 days

• Number of Participants With Change in Chest CT Visual Score

  180 days

• Chest CT Visual Score

  180 days

• Change in St. George's Respiratory Questionnaire (SGRQ)

  Baseline and Day 180

• Change in King's Brief Interstitial Lung Disease Questionnaire (KBILD)

  Baseline and Day 180

Study Arms (2)

Nintedanib

EXPERIMENTAL

150 mg PO twice a day, taken with food, (or, for Child-Pugh A patients, 100 mg by mouth twice daily).

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).

Drug: Placebo

Interventions

Nintedanib DRUG

150 mg PO twice a day, taken with food food (or, for Child-Pugh A patients, 100 mg by mouth twice daily).

Nintedanib

Placebo DRUG

placebo 150 mg equivalent twice a day, taken with food food (or, for Child-Pugh A patients, 100 mg by mouth twice daily).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Boehringer Ingelheim: collaborator

Study Sites (7)

Emory Healthcare Network

Atlanta, Georgia, 30322, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Mount Sinai Beth Israel

New York, New York, 10003, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Baylor University Medical Center Dallas

Dallas, Texas, 75246, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (1)

• 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.

  PMID: 40216412 DERIVED

MeSH Terms

Conditions

Pulmonary Fibrosis; Lung Diseases, Interstitial; Respiration Disorders; COVID-19; Cicatrix; Fibrosis

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Results Point of Contact

• Title: Dr. Maria Padilla
• Organization: Icahn School of Medicine at Mount Sinai

maria.padilla@mountsinai.org

212-241-5658

Study Officials

• Maria Padilla, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: * 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 6, 2020
• Study Start: November 18, 2020
• Primary Completion: February 1, 2024
• Study Completion: March 2, 2024
• Last Updated: April 30, 2026
• Results First Posted: April 30, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. Proposals should be directed to Maria.Padilla@mssm.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website

Locations

US (7)