Curosurf® in Adult Acute Respiratory Distress Syndrome Due to COVID-19

Study Overview
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Brief Summary
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Surfactant replacement therapy (SRT) improves oxygenation and survival in NRDS and some infant ARDS. SRT was tried in adult ARDS with conflicting results. Research by Filoche and Grotberg helped to understand the failure of previous clinical trials and yielded a strong scientific rationale for SRT success, now allowing to design a new administration protocol for SRT in adults, to be tested by this clinical trial in COVID-19 adult ARDS patients. Patients will be randomized to receive either a bronchial fibroscopy alone (with aspiration of secretions) or a bronchial fibroscopy with administration of 3 mL/kg of a solution of poractant alpha diluted to 16 mg/mL and distributed into each of the 5 lobar bronchi.

Official Title
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Randomized Controlled Phase II Trial of Poractant Alfa (Curosurf®) by Fiberoptic Bronchoscopy-directed Endobronchial Administration in Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19 Viral Pneumonia

Conditions
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COVID-19, ARDS, Human

Intervention / Treatment
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* Drug: poractant alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years Intensive care unit admission. Intubation and mechanical ventilation since less than 72h. Positive end-expiratory pressure ≥ 5 cmH2O. Acute respiratory distress syndrome following Berlin definition. COVID-19 PaO2/FiO2 ratio < 150 mmHg during at least 3 hours despite PEP trial. Compliance of the respiratory system < 50 mL/cmH2O Exclusion Criteria: Contraindication to prone position. Pregnancy. Weight < 40 kg height < 140 cm or height > 190 cm. Profuse bronchorrhea (at least 1 succion per hour during 3 hours). Other significant cause than ARDS to the respiratory failure. Decision to limit active therapies. No arterial line in place. Obesity with weight / height ratio > 1 kg / cm. Impossible to give neuromuscular blockers (e.g. drug unavailable owing to global pandemia). Severe chronic respiratory failure with oxygen at home. Other severe acute or chronic organ faillure (eg severe liver cirrhosis, severe chronic cardiac failure). History of pneumonectomy or pulmonary lobectomy. Patient scheduled for extracorporeal membrane oxygenation. Known hypersensibility to Curosurf. Contraindication to bronchial fibroscopy. Person under legal protection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surfactant arm<br>patient receiving the surfactant | Drug: poractant alfa<br>* Patient receiving surfactant (3 mL/kg of a poractant alpha solution diluted to 16 mg/mL, resulting in a total dose of 48mg/kg) administred by bronchial fibroscopy. The total volume will be divided in each of the five lobar bronchi.<br>|
| No Intervention: Control arm<br>patient not receiving the surfactant | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of the PaO2 / FiO2 ratio between the measurements taken before (t0) and one hour after the end of the invasive procedure (H1). |  | 1 hour post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygenation : PaO2 / FiO2 ratio. |  | up to Day 1 and up to Day 7 | 
| Oxygenation : area under the PaO2 / FiO2 curve. |  | up to Day 1 and up to Day 7 | 
| Oxygenation : area under the SpO2 curve. |  | up to Hour 1 and up to Hour 24 | 
| Evolution of thoraco-pulmonary compliance (mL / mbar) between before and one hour after the procedure. |  | 1 hour | 
| Overall survival rate |  | at 28 days, 56 days. | 
| Mortality rate at discharge from the intensive care unit. |  | through study completion, an average of 6 months. | 
| Mortality rate at discharge from the hospital. |  | through study completion, an average of 6 months. | 
| Number of ventilator-free days |  | Day 28, Day 56 | 
| Number of prone position sessions. |  | up to 56 days | 
| Time between inclusion and the last prone position session. |  | up to 56 days |