Nintedanib for treating lung fibrosis caused by COVID-19

"Nintedanib for the Treatment of SARS-Cov-2 Induced Pulmonary Fibrosis"

This study is testing if the drug nintedanib can help people with lung fibrosis caused by COVID-19 feel better and stop their condition from getting worse.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 250 (estimated)
• Ages: 18 Years to 89 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 1 site (Paris)
• Trial ID: NCT04541680 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy of nintedanib in patients who have developed pulmonary fibrosis as a result of SARS-CoV-2 infection. The study aims to determine if early intervention with nintedanib can inhibit the progression of lung fibrosis by blocking the activation of mesenchymal cells. Participants will be evaluated based on their hospitalization history for COVID-19 and lung opacities observed through high-resolution computed tomography (HRCT). The trial will compare the effects of nintedanib against a placebo in a Phase 3 setting.

Who should consider this trial

Good fit: Ideal candidates are individuals who were hospitalized for COVID-19 within the last 2 to 12 months and exhibit lung opacities with fibrotic features on HRCT.

Not a fit: Patients with pre-existing lung disorders or significant renal and liver dysfunction may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could significantly improve lung function and quality of life for patients suffering from COVID-19 induced pulmonary fibrosis.

How similar studies have performed: While there is limited data on the long-term effects of COVID-19 on lung health, similar approaches using antifibrotic agents have shown promise in other forms of pulmonary fibrosis.

Eligibility criteria

Inclusion Criteria:

* History of hospitalization for COVID-19 infection documented with positive PCR or positive serology in the previous 2 to 12 months
* Lung opacities on HRCT involving more than 10% of the lung volume, with fibrotic features
* DLCO≤ 70% of the predicted value

Exclusion Criteria:

* Pre-existing lung disorder with abnormal HRCT (including COPD, lung cancer, or pulmonary fibrosis)
* Laboratory parameter thresholds:
* renal insufficiency with following criteria: Creatinine clearance \<30 ml/min estimated by the Cockcroft-Gault equation.
* any of the following liver test criteria above the specified limit: Total bilirubin \> 1.5 above the upper limit of the normal range (ULN), except in patients with predominantly unconjugated hyperbilirubinemia (e.g., Gilbert's syndrome). Aspartate or alanine aminotransferase (AST or ALT) \>3 × ULN (refer to the protocol, Table 3 p 34 for the management of liver enzyme elevation).
* Recent surgery with wound healing in progress(\<7days )
* Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment).
* Significant pulmonary arterial hypertension (PAH) defined by any of the following:

  1. Previous clinical or echocardiographic evidence of significant right heart failure
  2. History of right heart catheterisation showing a cardiac index ≤2 L/min/m²
  3. PAH requiring parenteral therapy with epoprostenol/treprostinil.
* History of cardiovascular diseases, any of the following:

  1. Severe hypertension, uncontrolled under treatment (≥160/100 mmHg), within 6 months of Visit 1
  2. Myocardial infarction within 6 months of Visit 1
  3. Unstable cardiac angina within 6 months of Visit 1.
* Bleeding risk, any of the following:

  1. Known genetic predisposition to bleeding.
  2. Patients who require

  i. Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin) ii. High dose antiplatelet therapy.
* Alcohol or drug abuse which in the opinion of the treating physician would interfere with treatment.
* Ongoing or past antifibrotic treatment with pirfenidone or nintedanib
* Hypersensitivity to nintedanib, peanut or soya or to any of the excipients of the specialty Ofev®
* Patients not able to understand and follow study procedures including completion of self-administered questionnaires without help.
* No written informed consent from the patient
* Absence of affiliation to the French social security
* Participation in another interventional research

Where this trial is running

Paris

• Pneumologie — Paris, France (Recruiting)

Study contacts

• Study coordinator: Bruno Crestani, MD,PHD

Conditions SARS-Cov-2 Induced Pulmonary Fibrosis