Patients 2 to 6 months after Covid-19 acute pneumonia
Conditions
Interventions
Trade Name: OFEV 150 mg
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Nintedanib
CAS Number: 656247-17-5
Current Sponsor code: Nintedanib
Other descriptive name: NINTEDANIB
Concentration uni
Sponsors
Assistance Publique - Hôpitaux de Paris
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age > 18 years and =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: - Pre-existing lung disorder with abnormal HRCT (including COPD, lung cancer, or pulmonary fibrosis) - Recent surgery with wound healing in progress - 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: a. Previous clinical or echocardiographic evidence of significant right heart failure b. History of right heart catheterisation showing a cardiac index =2 L/min/m² c. PAH requiring parenteral therapy with epoprostenol/treprostinil. - History of cardiovascular diseases, any of the following: a. Severe hypertension, uncontrolled under treatment (=160/100 mmHg), within 6 months of Visit 1 b. Myocardial infarction within 6 months of Visit 1 c. Unstable cardiac angina within 6 months of Visit 1. - Bleeding risk, any of the following: a. Known genetic predisposition to bleeding. b. Patients who require i. Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin) ii. High dose antiplatelet therapy. - Pregnancy or lactation (women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using at least two methods of birth control from the date of consent to three months after the end of the patient study participation). - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to assess whether nintedanib slows the progression of lung fibrosis in COVID-19 survivors as assessed by the decline in the forced vital capacity (FVC) over 12 months compared to placebo;Secondary Objective: 1. To compare the rate of decline of DLCO over 12 months 2. To compare exercise capacity at 12 months 3. To compare high resolution CT (HRCT) lung fibrosis extension at 12 months 4. To compare change in health-related quality of life 5. To compare the evolution of dyspnea over time 6. To compare change in Depression and anxiety over time 7. To compare change in lung injury, pulmonary hypertension and inflammation biomarkers 8. To assess pulmonary hypertension prevalence at inclusion and 12 months 9. To assess association between genetic susceptibility (MUC5B polymorphism) and lung fibrosis in COVID-19 survivors 10. To assess safety of nintedanib;Primary end point(s): annual rate of decline in FVC from inclusion to 12 months, assessed by spirometry in accordance with international guidelines. Annual rate of decline in FVC will be estimated by linear regression from FVC measurements at inclusion and at 3, 6, 9 and 12 months.;Timepoint(s) of evaluation of this end point: LSLV | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Rate of decline in DLCO estimated by linear regression of DLCO from baseline to 12 months from DLCO measurement at inclusion, 6 and 12 months 2. Absolute change from baseline in the Six-minute walk test (6MWT) at 12 months 3. HRCT fibrosis score and HRCT fibrosis extension (visual and computer-based assessment) at inclusion and 12 months 4. Absolute change from baseline in the total score on the St. George’s Respiratory Questionnaire questionnaire at 12 months 5. Absolute change from baseline in the Dyspnea score (Multidimensional Dyspnea Profile and mMRC score) at 3, 6, 9 and 12 months 6. The absolute change from baseline Hospital Anxiety and Depression score at 3, 6, 9 and 12 months 7. Biomarker assay (KL-6, NT-proBNP, CRP, D-dimers) at inclusion and 12 months 8. Percentage of patients with a tricuspid regurgitation velocity > 2.5, 2.8 and 3.4 m/sec evaluated at baseline and at 12 months. 9. MUC5B at risk allele detection at inclusion 10. Incidence of clinical or biological adverse events with nintedanib versus placebo over 12 months ;Timepoint(s) of evaluation of this end point: LSLV | — |
Countries
France
Contacts
Public ContactProject Manager
Assistance Publique - Hôpitaux de Paris
Outcome results
None listed