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Poractant Alfa - Curosurf and SARS-COV-19 ARDS (Covid-19)

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ClinicalTrials.gov Identifier: NCT04502433
Recruitment Status : Recruiting
First Posted : August 6, 2020
Last Update Posted : August 6, 2021
Sponsor:
Information provided by (Responsible Party):
Chiesi Farmaceutici S.p.A.

Brief Summary:
The purpose of this Phase II -Proof of Concept study is to evaluate the efficacy and safety of poractant alfa (Curosurf®), administered by endotracheal (ET) instillation in adult hospitalized patients with SARS-COV-19 acute respiratory distress syndrome (ARDS)

Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Drug: CUROSURF® (poractant alfa) Phase 2

Detailed Description:

This is a multicentre, open-label, randomized phase II proof of concept study. The efficacy and safety of poractant alfa will be evaluated in terms of ventilatory free days during the 21 days after randomization, in adult patients with ARDS due to SARS-COV-19 infection.

Each patient randomized to the study treatment will receive three administrations of Curosurf ® with a 24 hours dosing interval.

The assessment collection will last until day 28 when the evaluation will occur at the ICU, or by phone call if the patient has been discharged before.

Seventy patients will be randomized in the study with a ratio 3:2 (i.e. 42 patients in the poractant alfa arm and 28 in the control arm).

The control arm population is treated as per Standard of Care (SoC).

This study will be conducted in UK, US and Italy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Seventy patients will be randomized in the study with a ratio 3:2 (i.e. 42 patients in the poractant alfa arm and 28 in the control arm).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Open-label, Randomised Trial to Assess the Efficacy and Tolerability of Poractant Alfa(Porcine Surfactant, Curosurf®) in Hospitalized Patients With SARS-COV-19 Acute Respiratory Distress Syndrome (ARDS)
Actual Study Start Date : January 6, 2021
Estimated Primary Completion Date : January 31, 2022
Estimated Study Completion Date : January 31, 2022


Arm Intervention/treatment
No Intervention: Control cohort

Approximately 28 patients will be included in this main control cohort.

The above-mentioned control cohort population will continue receiving the SoC

Experimental: Poractant alfa treated cohort
42 patients will be treated with CUROSURF® (poractant alfa).
Drug: CUROSURF® (poractant alfa)

Three administrations with a 24 hours dosing interval.

Each ET administration 1, 2, and 3 will consist of poractant alfa bolus:

30mg /kg (Lean Body Weight-LBW) = 0.375ml /kg LBW. Dilution with normal saline up to 2ml /kg LBW





Primary Outcome Measures :
  1. Number of days alive and ventilator-free days [ Time Frame: up to 21 days ]
    The primary outcome variable will be the number of days alive and ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation during the 21 days following randomisation.


Secondary Outcome Measures :
  1. Number of days alive and free from invasive ventilation [ Time Frame: at Day 21 day and at Day 28 ]
  2. Number of alive and free days from non-invasive ventilation (NIV) [ Time Frame: at Day 21 day and at Day 28 ]
  3. Change from baseline in PaO2/FiO2 ratio measured at 6 hours and 12 hours following administration of each dose in the treated group and at the similar time points in the control group [ Time Frame: 6, 12, 30, 36, 54 and 60 hours after randomisation ]
  4. Change from baseline in PaO2/FiO2 ratio at additional timepoints [ Time Frame: every 24 hours after treatment/randomisation until the patient is discharged from the ICU . Up to 28 days ]
  5. Length of ICU stay (days) [ Time Frame: up to 28 days ]
  6. Change from baseline in ventilatory parameter (Tidal volume- TV) [ Time Frame: up to 28 days ]
  7. Delta Sequential Organ Failure Assessment (SOFA) Score and sub-component measure [ Time Frame: Day3, and Day 28 or discharge whichever comes first ]
    min score 0 max score 24

  8. Incidence of all the AEs, AEs related to poractant alfa (treated cohort) (ADRs), serious AEs (SAEs) and AEs leading to death [ Time Frame: up to 28 days ]
  9. Change from baseline in blood gas analysis acid-base balance parameters (pH) [ Time Frame: up to 28 days ]
    Measured at 6-12-24h after each poractant alfa administration up to 72 hours and at similar timepoints in the control group (6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation) and then every 24 hours till the patient is discharged from the ICU

  10. Percentage of patients alive and with PaO2/ FiO2 improvement of >20% following administration of each dose in the treated group and at similar timepoints in the control group [ Time Frame: at 6 and 12 hours following administration each dose in the treated group and at similar timepoints in the control group = up to 60 hours after the randomization ]
  11. Percentage of patients alive and with PaO2/ FiO2 improvement of >20% following at the additional timepoints administration of each dose in the treated group and at similar time points in the control group [ Time Frame: through study completion, up to 28 days ]
  12. Change from baseline in FiO2 [ Time Frame: (6, 12, 30, 36, 54 and 60 hours after randomisation + every 24 hours after treatment/randomisation until the patient is discharged from the ICU = up to 28 days ]
  13. Change from baseline in ventilatory parameter (respiratory rate (RR)) [ Time Frame: up to 28 days ]
  14. Change from baseline in ventilatory parameter (dynamic compliance (Cdyn)) [ Time Frame: up to 28 days ]
  15. Change from baseline in ventilatory parameter (static compliance (Cstat)) [ Time Frame: up to 28 days ]
  16. Change from baseline in ventilatory parameter (positive end-expiratory pressure (PEEP) [ Time Frame: up to 28 days ]
  17. Change from baseline in ventilatory parameter (peak inspiratory pressure (PIP)) [ Time Frame: up to 28 days ]
  18. Change from baseline in ventilatory parameter (plateau pressure (Pplat)) [ Time Frame: up to 28 days ]
  19. Change from baseline in blood gas analysis acid-base balance parameter (pCO2) [ Time Frame: up to 28 days ]
  20. Change from baseline in blood gas analysis acid-base balance parameter (pO2) [ Time Frame: up to 28 days ]
  21. Change from baseline in blood gas analysis acid-base balance parameter (HCO3) [ Time Frame: up to 28 days ]
  22. Change from baseline in blood gas analysis acid-base balance parameter (lactate) [ Time Frame: up to 28 days ]
  23. Mortality [ Time Frame: up to day 28 ]
  24. Percentage of patients with improvement in severity status defined as a decrease in the severity score [ Time Frame: up to day 28 or discharge, whichever comes first ]
  25. Percentage of patients alive and out of ICU [ Time Frame: Day 28 ]
  26. Percentage of patients alive and free of organ failure [ Time Frame: at day 28 or discharge whichever comes first ]
  27. Percentage of patients alive and free of respiratory failure [ Time Frame: at Day 28 ]
  28. Number of days alive and ventilatory-free [ Time Frame: at day 28 ]

Other Outcome Measures:
  1. Change from baseline in lowest and dynamic surface tensions (mN/m) from Tracheal Aspirate (TA) samples [ Time Frame: at 12, 24, 48, 72 and 96 hrs after start of treatment (first dose in the poractant alfa group) or after randomisation (in the control group) ]
    exploratory endpoint for UK patients only

  2. Change from baseline in concentrations of surfactant phospholipids (mg/ml) from TA samples [ Time Frame: at 12, 24, 48, 72 and 96 hrs after start of treatment (first dose in the poractant alfa group) or after randomisation (in the control group) ]
    exploratory endpoint for UK patients only

  3. Change from baseline in concentrations of proteins (ng/ml) from TA samples [ Time Frame: at 12, 24, 48, 72 and 96 hrs after start of treatment (first dose in the poractant alfa group) or after randomisation (in the control group) ]
    exploratory endpoint for UK patients only

  4. Change from baseline in inflammatory indices such as cellular and cytokine (pg/ml) inflammatory markers (e.g. IL-1, IL-6, TNF alpha, IFN gamma, and lymphocyte markers) from TA and blood samples [ Time Frame: at 12, 24, 48, 72 and 96 hrs after start of treatment (first dose in the poractant alfa group) or after randomisation (in the control group) ]
    exploratory endpoint for UK patients only



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants are eligible to be included in the study if the following criteria apply:

  1. Male or female ≥18 and ≤ 80 years of age
  2. Informed consent for participation in the study (refer to section 15 for detailed inform consent procedure)
  3. Positive 2019-nCoV rt-PCR before randomisation
  4. PaO2/FiO2 ratio < 150 mmHg
  5. Lung compliance ≤45 ml/cmH20
  6. Intubated and artificially ventilated less than 48 hours before the first poractant alfa administration

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

  1. Any contraindications to surfactant administration e.g., pulmonary hemorrhage and pneumothorax)
  2. Weight < 40kg
  3. Stage 4 severe chronic kidney disease (i.e., eGFR < 30)
  4. Pregnancy
  5. Administration of any nebulized surfactant in the 48 hours before the first poractant alfa administration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04502433


Contacts
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Contact: Chiesi Clinical trial Info +39 0521 2791 clinicaltrials_info@chiesi.com

Locations
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United States, Michigan
Henry Ford Health System Not yet recruiting
Detroit, Michigan, United States, 48202
Contact: Kurt Kralovich, MD         
Italy
Chiesi site # 14 Not yet recruiting
Bologna, Italy, 40138
Chiesi site #13 Not yet recruiting
Modena, Italy, 41124
Contact: Busani, MD         
United Kingdom
UCLH and UCL 250 Euston Road Recruiting
London, United Kingdom, NW1 2BU
Contact: Howard Clark, MD         
Chiesi site #4 Not yet recruiting
London, United Kingdom, SW10 9NH
Chiesi site # 12 Not yet recruiting
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
Investigators
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Principal Investigator: Clark Howard, Prof. /MD University College, London
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Responsible Party: Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier: NCT04502433    
Other Study ID Numbers: CLI-050000-04
2020-002632-75 ( EudraCT Number )
First Posted: August 6, 2020    Key Record Dates
Last Update Posted: August 6, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Acute Lung Injury
Syndrome
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Poractant alfa
Pulmonary Surfactants
Respiratory System Agents