Acute Respiratory Distress Syndrome (ARDS) MedDRA version: 21.1 Level: LLT Classification code 10003083 Term: ARDS System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 24.0 Level: LLT Classification code 10085269 Term: ARDS disease progression System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
F4-Pharma GmbH i.G.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Hospitalised patients with mild to moderate ARDS according to the Berlin Definition of ARDS or patients with assisted breathing (without the use of PEEP) and high oxygen demand (e.g., HFNO = 30 L/min) who fulfil the other criteria of the Berlin Definition of ARDS (modified Berlin criteria) (for clarification see Table 1) 2. Patients = 18 years 3. Randomization within 48h of ARDS diagnosis 4. Written informed consent obtained prior to the initiation of any protocol-required procedures by the patient or his/her legal representative 5. Patients or their legal representatives able to understand the requirements of the study and give written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 217 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 46
Exclusion criteria
Exclusion criteria: 1. >48 hours of invasive mechanical ventilation before randomization 2. Severe ARDS according to the Berlin Definition 3. Evidence of other significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases with a bad prognosis that are likely to interfere with the evaluation of the patient’s safety and with the study outcome as judged by the treating physician, e.g.: o Other severe advanced or chronic lung diseases (e.g., COPD Gold = 3, severe silicosis) o Acute respiratory failure due to cardiac failure (NYHA = III) or fluid overload o Advanced hepatic insufficiency or severe liver disease (e.g., liver cirrhosis CHILD C) o Use of chronic (> 3 months) long-term oxygen therapy before randomization o Exacerbation of asthma o Septic shock 4. Any contraindications to use the IMP (e.g., allergy or intolerance against the IMP or its ingredients) 5. Is currently being detained in an institution by a governmental or judicial order 6. Do not intubate order 7. Women pregnant or breastfeeding 8. Males or females of reproductive potential not willing to use effective contraception for the duration of the study period (defined as PEARL index –1 - e.g., contraceptive pill, IUD or true sexual abstinence, bilateral tubal occlusion or male partner with vasectomy; also see chapter 19.2 for guidance) 9. Current participation in another interventional clinical trial with IMP or participation within the last 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate a difference in the time to initial unassisted breathing (UAB) in patients receiving FX06 compared to patients receiving placebo until day 28. • Time to initial unassisted breathing (UAB) until day 28 in both treatment groups Unassisted breathing is defined as: Without invasive ventilation for 48h consecutively for patients with invasive ventilation at BL and neither invasive nor non-invasive ventilation (including HFNO) for 48h consecutively for patients with non-invasive ventilation (including HFNO) at BL. Continuous or bilevel positive airway pressure (CPAP, BIPAP) solely for sleep-disordered breathing management is not defined as assisted breathing. Also, non-mechanical oxygen supplementation will not be defined as assisted breathing. ;Secondary Objective: - Disease progression/improvement based on Berlin Definition - Proportion of patients with respiratory support - days with ventilation and ventialtor-free days - days on ECMO - patients alive and UAB - patients that achieved initial UAB - patients achieving extubation - patients that needed intubation - patients returning to assisted breathing or mechanical ventilation - patients needing catecholamine hemodynamic support - patients receiving kinetic therapy - Lung function (e.g. PaO2, FiO2, Horowitz Index, pCO2, LPEEP, Pinsp, FiO2, vasodilator use, high-flow oxygen, oxygen saturation) - inflammation markers and their change and normalization - Mortality rate - Survival censored - normal and pathological capillary refill time - Length of hospital and ICU stay - Location where patients have been discharged to - Subgroup analysis by concomitant medication, age, sex, and ARDS cause - AEs/SAEs, type, severity and their relatedness to IMP - injection-related AEs;Primary end point(s): The primary objective is to demonstrate a difference in the time to initial unassisted breathing (UAB) in patients receiving FX06 compared to patients receiving placebo until d | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary objectives and endpoints: Assessment and treatment comparison of the following objectives at all available visits and time points between the FX06 and placebo group: • Disease progression/improvement - Proportion of patients with improved or worsened disease state compared to baseline based on Berlin Definition (mild, moderate, severe, or no ARDS) - Proportion of patients with each Berlin Definition classification (mild, moderate, severe, or no ARDS) - Proportion of patients with respiratory support (non-invasive, invasive, ECMO, HFNO, low flow oxygen, non-mechanical oxygen supplementation) - Number of days with ventilation (invasive vs non-invasive ventilation (incl. HFNO)) until day 28 and day 60 - Number of days on ECMO unitl day 28 and day 60 - Number of ventilator-free days until day 28 - Number and proportion of patients alive and breathing without assistance at day 28 and day 60 - Proportion of patients that achieved initial UAB within 28 days -Proportion of patients achieving extubation until day 28 and day 60 (for those patients intubated at BL) - Proportion of patients that needed intubation (invasive ventilation) until day 28 (for those patients that were not intubated at BL) - Proportion of patients returning to assisted breathing or mechanical ventilation (after achievement of initial UAB as defined above) - Proportion of patients needing catecholamine hemodynamic support to achieve target blood pressure and cumulative dosage of catecholamine drugs - Proportion of patients receiving kinetic therapy to improve pulmonary function and cumulative duration of prone positioning up to day 28 • Lung function (partial oxygen pressure in the blood, fraction of inspired oxygen, Horowitz index) at BL, D3, D6, D10 and D28 - Absolute PaO2 (mmHg) values - Absolute FiO2 (mmHg, fraction of inspired oxygen) - Horowitz Index (mmHg) and change to BL - pCO2 value and change to baseline - Lung compliance (ml/cm H2O) and change to BL - R | — |
Countries
Germany, Italy, Lithuania, Netherlands, Portugal, Romania, Spain
Contacts
Public ContactClinical Research
Fraunhofer ITMP
Outcome results
None listed