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

Study Purpose

Currently, there is no approved treatment for COVID-19 in France, either for the acute phase, nor for the late chronic phase. the investigator suggest that nintedanib has the potential to block the development of lung fibrosis when initiated early enough to inhibit the activation of mesenchymal cells and the progression of virus-induced pulmonary fibrosis. Computerized Tomography (CT) manifestations of fibrosis or fibrous stripes are described in COVID-19 (Ye, Eur Radiol 2020). Pan et al observed fibrous stripes in 17% patients in the early phase of the disease (Pan, Eur Radiol 2020). Ye et al observed bronchiectasis in 2 patients (15.4%) and evidence of pulmonary fibrosis in 3 patients (23.7%) at HRCT performed at 4 weeks (Ye, Eur Radiol 2020). Long term data are still lacking in patients with COVID-19 and the investigators do not know how many patients will have fibrotic sequelae from the acute illness.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 89 Years
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04541680
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Assistance Publique - Hôpitaux de Paris
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries France
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

SARS-Cov-2 Induced Pulmonary Fibrosis
Additional Details

At present, investigators have a very limited view on the long-term pulmonary sequelae after COVID-19 pneumonia, particularly in the most severe forms requiring hospitalization. Early thoracic HRCT is a useful tool for the evaluation of patients suspected of COVID-19 pneumonia. Typical features are evocative of the disease in an epidemic context, with multifocal ground-glass opacities, being nodular or not, or crazy-paving with or without consolidations, with a bilateral, peripheral or mixed distribution and involvement of the posterior zones. CT manifestations of fibrosis or fibrous stripes are described in COVID-19. Pan et al observed fibrous stripes in 17% patients in the early phase of the disease. Ye et al observed bronchiectasis in 2 patients (15.4%) and evidence of pulmonary fibrosis in 3 patients (23.7%) at HRCT performed at 4 weeks. Long term data are still lacking in patients with COVID-19 and the investigators do not know how many patients will have fibrotic sequelae from the acute illness.

Arms & Interventions

Arms

Experimental: Nintedanib

Experimental group will receive nintedanib 150mg BID for 12 months in addition to standard of care (SoC). Nintedanib dose could be reduced to 100mg BID depending on tolerance according to investigator in charge of the patient. The prescription of SoC drugs or procedure will be let to the choice of the investigator in charge of the patient.

Placebo Comparator: Placebo

Control group will receive Placebo BID for 12 months in addition to SoC. The prescription of SoC drugs or procedure will be let to the choice of the investigator in charge of the patient. Standard of care may include pulmonary rehabilitation.

Interventions

Drug: - Nintedanib 150 MG [Ofev]

Experimental group will receive nintedanib 150mg BID for 12 months in addition to standard of care (SoC). Nintedanib dose could be reduced to 100mg BID depending on tolerance according to investigator in charge of the patient. The prescription of SoC drugs or procedure will be let to the choice of the investigator in charge of the patient.

Other: - Placebo

Placebo

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Pneumologie, Paris, France

Status

Recruiting

Address

Pneumologie

Paris, , 95018

Site Contact

Crestani Bruno, MD

bruno.crestani@aphp.fr

0140256863