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

Sponsor
Chiesi Farmaceutici S.p.A. (Industry)
Overall Status
Terminated
CT.gov ID
NCT04502433
Collaborator
(none)
22
6
2
14.3
3.7
0.3

Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
22 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).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 :
Jan 6, 2021
Actual Primary Completion Date :
Mar 18, 2022
Actual Study Completion Date :
Mar 18, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Number of days alive and ventilator-free days [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 [at Day 21 day and at Day 28]

  2. Number of alive and free days from non-invasive ventilation (NIV) [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 [6, 12, 30, 36, 54 and 60 hours after randomisation]

  4. Change from baseline in PaO2/FiO2 ratio at additional timepoints [every 24 hours after treatment/randomisation until the patient is discharged from the ICU . Up to 28 days]

  5. Length of ICU stay (days) [up to 28 days]

  6. Change from baseline in ventilatory parameter (Tidal volume- TV) [up to 28 days]

  7. Delta Sequential Organ Failure Assessment (SOFA) Score and sub-component measure [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 [up to 28 days]

  9. Change from baseline in blood gas analysis acid-base balance parameters (pH) [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 [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 [through study completion, up to 28 days]

  12. Change from baseline in FiO2 [(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)) [up to 28 days]

  14. Change from baseline in ventilatory parameter (dynamic compliance (Cdyn)) [up to 28 days]

  15. Change from baseline in ventilatory parameter (static compliance (Cstat)) [up to 28 days]

  16. Change from baseline in ventilatory parameter (positive end-expiratory pressure (PEEP) [up to 28 days]

  17. Change from baseline in ventilatory parameter (peak inspiratory pressure (PIP)) [up to 28 days]

  18. Change from baseline in ventilatory parameter (plateau pressure (Pplat)) [up to 28 days]

  19. Change from baseline in blood gas analysis acid-base balance parameter (pCO2) [up to 28 days]

  20. Change from baseline in blood gas analysis acid-base balance parameter (pO2) [up to 28 days]

  21. Change from baseline in blood gas analysis acid-base balance parameter (HCO3) [up to 28 days]

  22. Change from baseline in blood gas analysis acid-base balance parameter (lactate) [up to 28 days]

  23. Mortality [up to day 28]

  24. Percentage of patients with improvement in severity status defined as a decrease in the severity score [up to day 28 or discharge, whichever comes first]

  25. Percentage of patients alive and out of ICU [Day 28]

  26. Percentage of patients alive and free of organ failure [at day 28 or discharge whichever comes first]

  27. Percentage of patients alive and free of respiratory failure [at Day 28]

  28. Number of days alive and ventilatory-free [at day 28]

Other Outcome Measures

  1. Change from baseline in lowest and dynamic surface tensions (mN/m) from Tracheal Aspirate (TA) samples [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 [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 [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 [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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Henry Ford Health System Detroit Michigan United States 48202
2 Chiesi site # 14 Bologna Italy 40138
3 Chiesi site #13 Modena Italy 41124
4 UCLH and UCL 250 Euston Road London United Kingdom NW1 2BU
5 Chiesi site #4 London United Kingdom SW10 9NH
6 Chiesi site # 12 Southampton United Kingdom SO16 6YD

Sponsors and Collaborators

  • Chiesi Farmaceutici S.p.A.

Investigators

  • Principal Investigator: Clark Howard, Prof. /MD, University College, London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier:
NCT04502433
Other Study ID Numbers:
  • CLI-050000-04
  • 2020-002632-75
First Posted:
Aug 6, 2020
Last Update Posted:
Apr 6, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 6, 2022