Poractant Alfa - Curosurf and SARS-COV-19 ARDS (Covid-19)
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 |
---|---|---|
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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
Arms and Interventions
Arm | Intervention/Treatment |
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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 |
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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
- 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
- Number of days alive and free from invasive ventilation [at Day 21 day and at Day 28]
- Number of alive and free days from non-invasive ventilation (NIV) [at Day 21 day and at Day 28]
- 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]
- 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]
- Length of ICU stay (days) [up to 28 days]
- Change from baseline in ventilatory parameter (Tidal volume- TV) [up to 28 days]
- 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
- 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]
- 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
- 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]
- 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]
- 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]
- Change from baseline in ventilatory parameter (respiratory rate (RR)) [up to 28 days]
- Change from baseline in ventilatory parameter (dynamic compliance (Cdyn)) [up to 28 days]
- Change from baseline in ventilatory parameter (static compliance (Cstat)) [up to 28 days]
- Change from baseline in ventilatory parameter (positive end-expiratory pressure (PEEP) [up to 28 days]
- Change from baseline in ventilatory parameter (peak inspiratory pressure (PIP)) [up to 28 days]
- Change from baseline in ventilatory parameter (plateau pressure (Pplat)) [up to 28 days]
- Change from baseline in blood gas analysis acid-base balance parameter (pCO2) [up to 28 days]
- Change from baseline in blood gas analysis acid-base balance parameter (pO2) [up to 28 days]
- Change from baseline in blood gas analysis acid-base balance parameter (HCO3) [up to 28 days]
- Change from baseline in blood gas analysis acid-base balance parameter (lactate) [up to 28 days]
- Mortality [up to day 28]
- 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]
- Percentage of patients alive and out of ICU [Day 28]
- Percentage of patients alive and free of organ failure [at day 28 or discharge whichever comes first]
- Percentage of patients alive and free of respiratory failure [at Day 28]
- Number of days alive and ventilatory-free [at day 28]
Other Outcome Measures
- 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
- 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
- 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
- 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
Inclusion Criteria:
Participants are eligible to be included in the study if the following criteria apply:
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Male or female ≥18 and ≤ 80 years of age
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Informed consent for participation in the study (refer to section 15 for detailed inform consent procedure)
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Positive 2019-nCoV rt-PCR before randomisation
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PaO2/FiO2 ratio < 150 mmHg
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Lung compliance ≤45 ml/cmH20
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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:
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Any contraindications to surfactant administration e.g., pulmonary hemorrhage and pneumothorax)
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Weight < 40kg
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Stage 4 severe chronic kidney disease (i.e., eGFR < 30)
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Pregnancy
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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.- CLI-050000-04
- 2020-002632-75