Clinical trial NCT04384731: Curosurf® in Adult Acute Respiratory Distress Syndrome Due to COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19
ARDS, Human
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
First posted: 2020-05-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Evolution of the PaO2 / FiO2 ratio between the measurements taken before (t0) and one hour after the end of the invasive procedure (H1).
timeFrame: 1 hour post treatment
Secondary outcomes:
measure: Oxygenation : PaO2 / FiO2 ratio.
timeFrame: up to Day 1 and up to Day 7
measure: Oxygenation : area under the PaO2 / FiO2 curve.
timeFrame: up to Day 1 and up to Day 7
measure: Oxygenation : area under the SpO2 curve.
timeFrame: up to Hour 1 and up to Hour 24
measure: Evolution of thoraco-pulmonary compliance (mL / mbar) between before and one hour after the procedure.
timeFrame: 1 hour
measure: Overall survival rate
timeFrame: at 28 days, 56 days.
measure: Mortality rate at discharge from the intensive care unit.
timeFrame: through study completion, an average of 6 months.
measure: Mortality rate at discharge from the hospital.
timeFrame: through study completion, an average of 6 months.
measure: Number of ventilator-free days
timeFrame: Day 28, Day 56
measure: Number of prone position sessions.
timeFrame: up to 56 days
measure: Time between inclusion and the last prone position session.
timeFrame: up to 56 days
Other outcomes:
Locations:
city: Mantes la Jolie
country: France
facility: CH Francois Quesnay
Study officials:
affiliation: Hospital of Mantes-la-Jolie, France
name: Christophe LENCLUD, MD
role: PRINCIPAL_INVESTIGATOR
References: