Curosurf® in Adult Acute Respiratory Distress Syndrome Due to COVID-19 (Caards-1)

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

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.

Study Overview

• Status: Recruiting
• Conditions: COVID-19; ARDS, Human
• Intervention / Treatment: Drug: poractant alfa

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sandrine ROUX; Phone Number: +33139239777; Email: sroux@ch-versailles.fr

Study Locations

• France
  • Mantes la Jolie, France
    • Recruiting
    • CH Francois Quesnay
    • Contact: Christophe LENCLUD, MD
    • Principal Investigator: Chrstophe LENCLUD, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surfactant arm; patient receiving the surfactant	Drug: poractant alfa; 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.
No Intervention: Control arm; patient not receiving the surfactant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Dr Christophe LENCLUD
• Investigators: Principal Investigator: Christophe LENCLUD, MD, Hospital of Mantes-la-Jolie, France

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2020
• Primary Completion (Anticipated): May 29, 2021
• Study Completion (Anticipated): July 31, 2021

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 12, 2020

Study Record Updates

• Last Update Posted (Actual): February 3, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Respiratory System Agents; Pulmonary Surfactants; Poractant alfa
• Other Study ID Numbers: P20/06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No