Acute Respiratory Distress SyndromePhase 2NCT04502433
Poractant Alfa (Curosurf®)) -- Effect in Adult Patients Diagnosed With 2019 Novel Coronavirus (SARS-COV-19; (Covid-19)) Acute Respiratory Distress Syndrome (ARDS)
A Phase 2 study testing CUROSURF® (poractant alfa) in people with Acute Respiratory Distress Syndrome, run by Chiesi Farmaceutici S.p.A. at 6 sites in 3 countries.
Trial summary
The purpose of this study was to evaluate the efficacy and safety of poractant alfa (Curosurf®), administered by endotracheal (ET) instillation in hospitalized adult patients diagnosed with SARS-COV-19 acute respiratory distress syndrome (ARDS). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- CUROSURF® (poractant alfa)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 6 Jan 2021to 17 Mar 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants were eligible to be included in the study if the following criteria apply:
- Male or female ≥18 and ≤ 80 years of age
- Informed consent for participation in the study (refer to section 15 for detailed inform consent procedure)
- Positive 2019-nCoV Reverse Transcription Polymerase Chain Reaction (rt-PCR) before randomisation
- Arterial Partial Pressure of Oxygen/Fraction of Inspired Oxygen (PaO2/FiO2) ratio < 150 mmHg
- Lung compliance ≤45 ml/cmH20
- Intubated and artificially ventilated less than 48 hours before the first poractant alfa administration
Who cannot join
- Participants were excluded from the study if any of the following criteria apply:
- Any contraindications to surfactant administration e.g., pulmonary hemorrhage and pneumothorax)
- Weight < 40kg
- Stage 4 severe chronic kidney disease (i.e., Estimated Glomerular Filtration Rate (eGFR) < 30)
- Pregnancy
- Administration of any nebulized surfactant in the 48 hours before the first poractant alfa administration
- Extracorporeal membrane oxygenation (ECMO)
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United Kingdom3 sites
UCLH and UCL 250 Euston Road
London, NW1 2BU
Chiesi site #4
London, SW10 9NH
Chiesi site # 12
Southampton, SO16 6YD
About this study
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)
The purpose of this study was to evaluate the efficacy and safety of poractant alfa (Curosurf®), administered by endotracheal (ET) instillation in hospitalized adult patients diagnosed with SARS-COV-19 acute respiratory distress syndrome (ARDS).
Read the detailed description
This was a multicentre, open-label, randomized phase II proof-of-concept study.
The efficacy and safety of poractant alfa was evaluated in terms of ventilatory free days during the 21 days after randomization, in adult patients diagnosed with ARDS due to SARS-COV-19 infection.
Each patient randomized to the study treatment received 3 administrations of Curosurf ® with a 24 hours dosing interval. The assessment collection was up to Day 28, when the evaluation occurred at the Intensive Care Unit (ICU), or by phone call if the patient has already been discharged.
Seventy patients were planned to 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 received Standard of Care (SoC). This study was conducted in United Kingdom (UK), United States of America (US), and Italy.
Overall, 13 patients (Curosurf ® group) and 8 patients (control group) were randomised in the study. Due to low recruitment rate the study was terminated early for non-safety reasons.
Curosurf® is a pulmonary surfactant of natural origin which, when delivered endotracheally (ET). Curosurf® is currently approved for marketing as treatment of premature neonates with RDS or at risk of Respiratory Distress Syndrome (RDS). Chiesi Farmaceutici S.p.A (Chiesi) conducted this study with its porcine-derived surfactant, Curosurf® (poractant alfa), to evaluate the efficacy and safety in ventilated adult patients who were critically unwell in intensive care with SARS-COV-19 ARDS.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- CUROSURF® (poractant alfa)
- Keywords
- acute respiratory distress syndrome, ARDS, Adults, Surfactant, Poractant alfa (porcine surfactant, Curosurf®),, Curosurf®, Coronavirus disease (COVID-19), Coronavirus 2019 Disease
- Medical subject headings
- Respiratory Distress Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CUROSURF® (poractant alfa)Drug
Three administrations with a 24 hours dosing interval.
Each endotracheal (ET) administration 1, 2, and 3 consisted of poractant alfa bolus:
30mg /kg (Lean Body Weight-LBW) = 0.375ml /kg LBW, diluted with normal saline up to 2ml /kg LBW.
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | Patients treated with standard-of-care (SoC), as control cohort |
| Poractant alfa | Experimental | Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC) Receives: Drug: CUROSURF® (poractant alfa) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Days Alive and Ventilator-free Days
The number of days alive and ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation over the 21 days following randomisation.
Mechanical ventilation was defined as invasive and non-invasive. The patient was defined as free of mechanical ventilation after 12 hours from the suspension of either invasive and non-invasive ventilation. Patients who died or were mechanically ventilated longer than this period were assessed as zero ventilator-free days.
Measured: up to 21 days
Secondary outcomes (26)
Percentage of Patients Alive and Free of Respiratory Failure at Day 28
The percentage of patients alive and free of respiratory failure (i.e. without need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), non-invasive ventilation, or high-flow nasal cannula oxygen delivery) at Day 28.
Measured: at Day 28
Number of Days Alive and Ventilator-Free at Day 28
The number of days alive and ventilator-free (i.e. free of any mechanical ventilation for at least 12 hours) at Day 28.
Measured: at Day 28
Mortality at Day 21 and Day 28
Mortality at Day 21 and Day 28 of the study by treatment group.
Measured: at Day 21 and at Day 28
Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28
The number of days alive and free from invasive ventilation at Day 21 and Day 28 is presented by treatment group.
Measured: Day 21 and Day 28
Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28
The number of days alive and free from non-invasive ventilation at Day 21 and Day 28 is presented by treatment group.
Measured: Day 21 and Day 28
Percentage of Patients With Improvement in Severity Status at Day 28 or Discharge (Severity Score: Mild, Moderate, Severe, or Death)
The severity status of patients at baseline and at Day 28/Discharge and the percentage of patients with improvement in severity status (i.e. a decrease of at least 1 point in severity status) at Day 28/Discharge relative to baseline is presented.
Severity was assessed using a point score system: Severity score was defined as mild, moderate, severe (see below*), or death and was based on PaO2/FiO2 ratio and patient status at Day 28/Discharge and numerically rated from 1-4, respectively. An improvement in severity was defined as a decrease of at least 1 point between baseline and Day 28/Discharge.
At Day 28 the last follow up evaluation took place on the ICU if, still requiring critical care, or by phone call if the patient has been discharged from ICU by that time.
*Mild: 200 mmHg < PaO2/FiO2 ratio ≤300 mmHg; Moderate: 100 mmHg < PaO2/FiO2 ratio ≤200 mmHg; Severe: PaO2/FiO2 ratio ≤100 mmHg
Measured: Day 28 or Discharge, whichever comes first
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint
Change from baseline in PaO2/FiO2 ratio measured at each timepoint following administration of each dose in the treatment and control group.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
Partial pressure of oxygen (PaO2) is the oxygen pressure in arterial blood. The fraction of inspired oxygen (FiO2) is the concentration of oxygen in the gas mixture.
The fraction of inspired oxygen (PaO2/FiO2) ratio is widely used in ICUs as an indicator of oxygenation status.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint
The percentages of patients in categories of PaO2/FiO2 ratio improvement compared to baseline (>20%) at all timepoints post-baseline are summarised by treatment group.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint
The FiO2 at baseline and at selected timepoints post-baseline was measured. Results are shown as changes from baseline, summarised by treatment group.
The change was calculated from two time points as the value at the later time point minus the value at baseline. The unit for the variable is percent (%) and what is reported is an absolute change.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Length of ICU Stay (Days) at Day 28
The length of ICU stay (days) at Day 28 is presented by treatment by treatment group. Patients who died or were mechanically ventilated longer than this period were assigned with 28 days.
Measured: up to 28 days
Percentage of Patients Alive and Out of Intensive Care Unit (ICU) at Day 28
The percentage of patients alive and out of ICU at Day 28 is presented by treatment group.
Measured: Day 28
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28
The Sequential Organ Failure Assessment (SOFA) score is a scoring system that assesses the performance of several organ systems in the body. The SOFA score was used to determine the extent of organ failure at Day 3 and Day 28/Discharge with respect to a pre-randomisation assessment.
The total score was derived from six sub-scores system categories: respiratory, neurological, cardiovascular, hepatic, coagulation, and renal systems; respective sub-scores were calculated primarily considering PaO2/FiO2 ratio, Glasgow Coma Scale, mean arterial pressure (MAP) or requirement for vasopressor administration, bilirubin levels, platelet levels and creatinine levels or daily urine output.
A score of 0, 1, 2, 3, or 4) was assigned to each of the six system category. The total score ranged from 0 (min) to 24 (max) points. To be considered organ failure free, a patient had to have a score of 0.
Measured: Day 3 and Day 28 or discharge -- whichever comes first
Percentage of Patients Alive and Free of Organ Failure (SOFA Score=0)
The percentage of patients alive and organ failure free (defined as SOFA score=0) at Day 28/Discharge is presented by treatment group.
The total score was derived from six sub-scores system categories: respiratory, neurological, cardiovascular, hepatic, coagulation, and renal systems; respective sub-scores were calculated primarily considering PaO2/FiO2 ratio, Glasgow Coma Scale, mean arterial pressure (MAP) or requirement for vasopressor administration, bilirubin levels, platelet levels and creatinine levels or daily urine output.
A score of 0, 1, 2, 3, or 4) was assigned to each of the six system category. The total score ranged from 0 (min) to 24 (max) points. To be considered organ failure free, a patient had to have a score of 0.
Measured: at day 28 or discharge -- whichever comes first
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Change from baseline in tidal volume (mL/kg BW) at all timepoints up to Day 3 (72 hours) and at Day 28.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
Tidal volume is the amount of air that moves in or out of the lungs with each respiratory cycle.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Change from baseline in respiratory rate (breaths/minute) at all timepoints up to Day 3 (72 hours) and at Day 28.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
Respiratory rate is the number of breaths taken per minute.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Change from baseline in dynamic compliance (mL/cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
Dynamic compliance: is the continuous measurement of pulmonary compliance calculated at each point representing schematic changes during rhythmic breathing. Dynamic compliance monitors both elastic and airway resistance.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: static compliance -- change from baseline in static compliance (mL/cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
At each time point the number of patients that contributed with a result value is indicated for both study arms.
Static Compliance: represents pulmonary compliance at a given fixed volume when there is no airflow, and muscles are relaxed.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Positive End-Expiratory Pressure -- Change from baseline in PEEP (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
At each time point the number of patients that contributed with a result value is indicated for both study arms.
Positive end-expiratory pressure (PEEP) is the positive pressure that will remain in the airways at the end of the respiratory cycle (end of exhalation) that is greater than the atmospheric pressure in mechanically ventilated patients.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Peak Inspiratory Pressure -- Change from baseline in peak inspiratory pressure (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
At each time point the number of patients that contributed with a result value is indicated for both study arms.
Peak inspiratory pressure (PIP) is the highest level of pressure applied to the lungs during inhalation. In mechanical ventilation the number reflects a positive pressure in centimetres of water pressure (cmH2O).
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Plateau Pressure -- Change from baseline in plateau pressure (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
At each time point the number of patients that contributed with a result value is indicated for both study arms.
Plateau pressure is the pressure that is applied by the mechanical ventilator to the small airways and alveoli.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH
Change from baseline in blood gas analysis acid-base balance parameters -- pH.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2)
Change from baseline in blood gas analysis acid-base balance parameter -- pCO2.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2)
Change from baseline in blood gas analysis acid-base balance parameter -- pO2.
The change was calculated from two time points as the value at the later time point minus the value at baseline.
Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3)
Change from baseline in blood gas analysis acid-base balance parameter -- Bicarbonate (HCO3).
The change was calculated from two time points as the value at the later time point minus the value at baseline.
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
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Change From Baseline in Blood Parameter -- Lactate
Change from baseline in blood parameter -- Lactate
The change was calculated from two time points as the value at the later time point minus the value at baseline.
At each time point the number of patients that contributed with a result value is indicated for both study arms.
Arterial blood lactate was measured at 6, 12, 24, 30, 36, 48, 54, 60, and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.
Measured: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Mortality -- TEAEs Leading to Death
The incidence of treatment-emergent adverse event (TEAEs) leading to death is presented by treatment group.
Measured: up to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2020
- Study start6 Jan 2021
- Primary completion17 Mar 2022
- Study completion17 Mar 2022
Why it stopped: The enrolment was extended. Nevertheless, despite the Sponsor's attempts, the infection status did not permit the identification of eligible patients for the study to complete it in a reasonable time.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Chiesi Farmaceutici S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clark Howard, Prof. /MD, Principal investigator, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04502433
- Sponsor's protocol ID
- CLI-050000-04
- Other IDs
- 2020-002632-75
- Status last verified
- May 2023
- First submitted
- 3 Aug 2020
- Last updated
- 23 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04502433
- Acronym / sponsor ID
- CLI-050000-04
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- acute respiratory distress syndrome, ARDS, Adults, Surfactant, Poractant alfa (porcine surfactant, Curosurf®),, Curosurf®, Coronavirus disease (COVID-19), Coronavirus 2019 Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The enrolment was extended. Nevertheless, despite the Sponsor's attempts, the infection status did not permit the identification of eligible patients for the study to complete it in a reasonable time.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Chiesi Farmaceutici S.p.A.Industry (pharma, biotech, devices)
- Study start
- 6 Jan 2021 (actual)
- Primary completion
- 17 Mar 2022 (actual)
- Study completion
- 17 Mar 2022 (actual)
- First posted
- 6 Aug 2020 (actual)
- Results
- Posted 23 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to evaluate the efficacy and safety of poractant alfa (Curosurf®), administered by endotracheal (ET) instillation in hospitalized adult patients diagnosed with SARS-COV-19 acute respiratory distress syndrome (ARDS).
Detailed description
This was a multicentre, open-label, randomized phase II proof-of-concept study.
The efficacy and safety of poractant alfa was evaluated in terms of ventilatory free days during the 21 days after randomization, in adult patients diagnosed with ARDS due to SARS-COV-19 infection.
Each patient randomized to the study treatment received 3 administrations of Curosurf ® with a 24 hours dosing interval. The assessment collection was up to Day 28, when the evaluation occurred at the Intensive Care Unit (ICU), or by phone call if the patient has already been discharged.
Seventy patients were planned to 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 received Standard of Care (SoC). This study was conducted in United Kingdom (UK), United States of America (US), and Italy.
Overall, 13 patients (Curosurf ® group) and 8 patients (control group) were randomised in the study. Due to low recruitment rate the study was terminated early for non-safety reasons.
Curosurf® is a pulmonary surfactant of natural origin which, when delivered endotracheally (ET). Curosurf® is currently approved for marketing as treatment of premature neonates with RDS or at risk of Respiratory Distress Syndrome (RDS). Chiesi Farmaceutici S.p.A (Chiesi) conducted this study with its porcine-derived surfactant, Curosurf® (poractant alfa), to evaluate the efficacy and safety in ventilated adult patients who were critically unwell in intensive care with SARS-COV-19 ARDS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –Patients treated with standard-of-care (SoC), as control cohort |
| Poractant alfa | Experimental | Drug: CUROSURF® (poractant alfa)Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female ≥18 and ≤ 80 years of age
- Informed consent for participation in the study (refer to section 15 for detailed inform consent procedure)
- Positive 2019-nCoV Reverse Transcription Polymerase Chain Reaction (rt-PCR) before randomisation
- Arterial Partial Pressure of Oxygen/Fraction of Inspired Oxygen (PaO2/FiO2) ratio < 150 mmHg
- Lung compliance ≤45 ml/cmH20
Key exclusion criteria (7 listed)
- Any contraindications to surfactant administration e.g., pulmonary hemorrhage and pneumothorax)
- Weight < 40kg
- Stage 4 severe chronic kidney disease (i.e., Estimated Glomerular Filtration Rate (eGFR) < 30)
- Pregnancy
- Administration of any nebulized surfactant in the 48 hours before the first poractant alfa administration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CUROSURF® (poractant alfa)Three administrations with a 24 hours dosing interval. Each endotracheal (ET) administration 1, 2, and 3 consisted of poractant alfa bolus: 30mg /kg (Lean Body Weight-LBW) = 0.375ml /kg LBW, diluted with normal saline up to 2ml /kg LBW. | Drug | Poractant alfa |
Primary outcome
Number of Days Alive and Ventilator-free Days
Time frame: up to 21 days
The number of days alive and ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation over the 21 days following randomisation. Mechanical ventilation was defined as invasive and non-invasive. The patient was defined as free of mechanical ventilation after 12 hours from the suspension of either invasive and non-invasive ventilation. Patients who died or were mechanically ventilated longer than this period were assessed as zero ventilator-free days.
26 secondary outcomes
Percentage of Patients Alive and Free of Respiratory Failure at Day 28
Time frame: at Day 28
Number of Days Alive and Ventilator-Free at Day 28
Time frame: at Day 28
Mortality at Day 21 and Day 28
Time frame: at Day 21 and at Day 28
Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28
Time frame: Day 21 and Day 28
Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28
Time frame: Day 21 and Day 28
Percentage of Patients With Improvement in Severity Status at Day 28 or Discharge (Severity Score: Mild, Moderate, Severe, or Death)
Time frame: Day 28 or Discharge, whichever comes first
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Length of ICU Stay (Days) at Day 28
Time frame: up to 28 days
Percentage of Patients Alive and Out of Intensive Care Unit (ICU) at Day 28
Time frame: Day 28
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28
Time frame: Day 3 and Day 28 or discharge -- whichever comes first
Percentage of Patients Alive and Free of Organ Failure (SOFA Score=0)
Time frame: at day 28 or discharge -- whichever comes first
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2)
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2)
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3)
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Change From Baseline in Blood Parameter -- Lactate
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Mortality -- TEAEs Leading to Death
Time frame: up to day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Study Record on EU Clinical Trials Register including resultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clark Howard, Prof. /MD principal investigator
University College, London
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CUROSURF® (poractant alfa) in people with Acute Respiratory Distress Syndrome, run by Chiesi Farmaceutici S.p.A. at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United Kingdom, Italy, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Days Alive and Ventilator-free Days (time frame: up to 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2023.