Clinical Trial Results:
A randomized double-blind placebo-controlled, pilot trial of intravenous plasma-purified alpha-1 antitrypsin for severe COVID-19 illness.
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Summary
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EudraCT number |
2020-001391-15 |
Trial protocol |
IE |
Global end of trial date |
12 Apr 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Jun 2022
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First version publication date |
26 Jun 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
V323Oct2020
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Royal College of Surgeons Ireland
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Sponsor organisation address |
111 St Stephens Green, Dublin, Ireland, Dublin 2
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Public contact |
Mandy Jackson, Royal College of Surgeons Ireland, +353 852147569, mandyjackson@Rcsi.ie
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Scientific contact |
Mandy Jackson, Royal College of Surgeons Ireland, +353 852147569, mandyjackson@Rcsi.ie
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Sep 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Apr 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Apr 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The aim of the study is to conduct a clinical trial of IV AAT as a prospective anti-inflammatory therapy for severely ill COVID-19 patients with ARDS requiring ICU admission.
The primary objective is to demonstrate a biological effect of IV Prolastin administered weekly at 120mg per kilogram of body weight in patients with severe COVID-19 illness requiring intubation and mechanical ventilation for ARDS by reducing circulating levels of IL-6 as measured by plasma ELISA. The study sample size is sufficient to demonstrate a significant difference in patients receiving Prolastin versus patients receiving placebo.
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Protection of trial subjects |
Assent was provided by next of kin for those subjects unable to consent. Adequate time was always given to allow patients/patients next of kin to fully understand the study and ask any questions. In addition, attempts were always made to have subjects sign the consent form themselves if they regained capacity.
Where any participant was enrolled and did not regain capacity (due to their death or neurological impairment) the default position was that the enrolled person continued to be a participant in the trial. This was approved by the consent declaration granted by the Health Research Consent Declaration Committee.
After the 10th patient was enrolled in the trial, an interim analysis was carried out by the RCSI Statistician and data was presented to two independent physicians, following which a decision regarding whether or not to proceed was undertaken
based on (1) safety and tolerability, and (2) the status of the primary endpoint.
Regular adverse event checks at each patient visit ensured continuous safety monitoring of participants.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Apr 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Ireland: 36
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Worldwide total number of subjects |
36
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EEA total number of subjects |
36
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
24
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From 65 to 84 years |
12
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients (n=36) were enrolled between April 20, 2020, and March 18, 2021. Hospitalized patients with a working diagnosis of Acute Respiratory Distress Syndrome (ARDS) secondary to COVID-19 were screened on arrival to the ICU. | |||||||||||||||
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Pre-assignment
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Screening details |
Eligible patients were aged ≥18 years, had a laboratory confirmed diagnosis of COVID-19, and were receiving ventilator support for moderate-to-severe ARDS with PaO2:FIO2 <200mmHg. In all patients diagnosed with COVID-19, SARS-CoV-2 infection was confirmed by RT-PCR of a nasopharyngeal swab specimen. | |||||||||||||||
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Period 1
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Period 1 title |
Baseline
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||||||||
Blinding implementation details |
Designated unblinded trial personnel were used to randomise subjects and prepare the study drug. The study drug was placed into opaque infusion masking bags so that the active could not be differentiated from placebo. In addition, the giving sets used were red which masked the colour of the study drug and the infusion lines were pre-primed by unblinded personnel. These measures then allowed the infusion to be transported and administered by a blinded member of the team.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo Arm (Baseline) | |||||||||||||||
Arm description |
0.9% sodium chloride | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
0.9% sodium chloride
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Investigational medicinal product code |
ATC code: B05XX
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Other name |
NaCL
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Infusion
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Dosage and administration details |
The placebo to be used in the study is 0.9% sodium chloride solution for infusion (“normal
saline”). Composition: 9.0 g/l sodium chloride (NaCl) in sterile water for injection. Each ml contains 9
mg sodium chloride. mmol/l: Na+ : 154 Cl- : 154. pH: 4.5-7.
If randomised to Group 1, the dosing was as follows:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
-- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
If randomised to Group 3, the dosing was as follows:
- Week 1: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
Group 2 did not contain any placebo administration.
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Arm title
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Plasma Purified Alpha-1 antitrypsin (Baseline) | |||||||||||||||
Arm description |
The intervention used was human plasma-purified alpha-1 antitrypsin (Prolastin) | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Human plasma-purified alpha-1 antitrypsin
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Investigational medicinal product code |
ATCcode: B02AB02
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Other name |
Prolastin
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Pharmaceutical forms |
Powder and solvent for solution for infusion
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Routes of administration |
Solution for infusion
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Dosage and administration details |
Group 1:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
Group 2:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 3: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 4: Prolastin 120mg/kg body weight IV over 60 minutes*
Group 3 was placebo only and no Prolastin
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Period 2
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Period 2 title |
Day 2
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||||||||
Blinding implementation details |
Designated unblinded trial personnel were used to randomise subjects and prepare the study drug. The study drug was placed into opaque infusion masking bags so that the active could not be differentiated from placebo. In addition, the giving sets used were red which masked the colour of the study drug and the infusion lines were pre-primed by unblinded personnel. These measures then allowed the infusion to be transported and administered by a blinded member of the team.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo Arm (Day 2) | |||||||||||||||
Arm description |
0.9% sodium chloride | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
0.9% sodium chloride
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Investigational medicinal product code |
ATC code: B05XX
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Other name |
NaCL
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Infusion
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Dosage and administration details |
The placebo to be used in the study is 0.9% sodium chloride solution for infusion (“normal
saline”). Composition: 9.0 g/l sodium chloride (NaCl) in sterile water for injection. Each ml contains 9
mg sodium chloride. mmol/l: Na+ : 154 Cl- : 154. pH: 4.5-7.
If randomised to Group 1, the dosing was as follows:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
-- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
If randomised to Group 3, the dosing was as follows:
- Week 1: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
Group 2 did not contain any placebo administration.
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Arm title
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Plasma Purified Alpha-1 antitrypsin (Day 2) | |||||||||||||||
Arm description |
The intervention used was human plasma-purified alpha-1 antitrypsin (Prolastin) | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Human plasma-purified alpha-1 antitrypsin
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Investigational medicinal product code |
ATCcode: B02AB02
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Other name |
Prolastin
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Pharmaceutical forms |
Powder and solvent for solution for infusion
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Routes of administration |
Solution for infusion
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Dosage and administration details |
Group 1:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
Group 2:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 3: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 4: Prolastin 120mg/kg body weight IV over 60 minutes*
Group 3 was placebo only and no Prolastin
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Period 3
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Period 3 title |
Day 7 (post-infusion)
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo Arm (Day 7) | |||||||||||||||
Arm description |
0.9% sodium chloride | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
0.9% sodium chloride
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Investigational medicinal product code |
ATC code: B05XX
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Other name |
NaCL
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Infusion
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Dosage and administration details |
The placebo to be used in the study is 0.9% sodium chloride solution for infusion (“normal
saline”). Composition: 9.0 g/l sodium chloride (NaCl) in sterile water for injection. Each ml contains 9
mg sodium chloride. mmol/l: Na+ : 154 Cl- : 154. pH: 4.5-7.
If randomised to Group 1, the dosing was as follows:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
-- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
If randomised to Group 3, the dosing was as follows:
- Week 1: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
Group 2 did not contain any placebo administration.
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Arm title
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Plasma Purified Alpha-1 antitrypsin (Day 7) | |||||||||||||||
Arm description |
The intervention used was human plasma-purified alpha-1 antitrypsin (Prolastin) | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Human plasma-purified alpha-1 antitrypsin
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Investigational medicinal product code |
ATCcode: B02AB02
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Other name |
Prolastin
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Pharmaceutical forms |
Powder and solvent for solution for infusion
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Routes of administration |
Solution for infusion
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Dosage and administration details |
Group 1:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
Group 2:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 3: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 4: Prolastin 120mg/kg body weight IV over 60 minutes*
Group 3 was placebo only and no Prolastin
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Period 4
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Period 4 title |
Day 28
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo Arm (Day 28) | |||||||||||||||
Arm description |
0.9% sodium chloride | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
0.9% sodium chloride
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Investigational medicinal product code |
ATC code: B05XX
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Other name |
NaCL
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Infusion
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Dosage and administration details |
The placebo to be used in the study is 0.9% sodium chloride solution for infusion (“normal
saline”). Composition: 9.0 g/l sodium chloride (NaCl) in sterile water for injection. Each ml contains 9
mg sodium chloride. mmol/l: Na+ : 154 Cl- : 154. pH: 4.5-7.
If randomised to Group 1, the dosing was as follows:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
-- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
If randomised to Group 3, the dosing was as follows:
- Week 1: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
Group 2 did not contain any placebo administration.
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Arm title
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Plasma Purified Alpha-1 antitrypsin (Day 28) | |||||||||||||||
Arm description |
The intervention used was human plasma-purified alpha-1 antitrypsin (Prolastin) | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Human plasma-purified alpha-1 antitrypsin
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Investigational medicinal product code |
ATCcode: B02AB02
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Other name |
Prolastin
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Pharmaceutical forms |
Powder and solvent for solution for infusion
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Routes of administration |
Solution for infusion
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Dosage and administration details |
Group 1:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 3: Placebo (same volume, same rate of infusion as for Prolastin)
- Week 4: Placebo (same volume, same rate of infusion as for Prolastin)
Group 2:
- Week 1: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 2: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 3: Prolastin 120mg/kg body weight IV over 60 minutes*
- Week 4: Prolastin 120mg/kg body weight IV over 60 minutes*
Group 3 was placebo only and no Prolastin
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Baseline characteristics reporting groups
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Reporting group title |
Placebo Arm (Baseline)
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Reporting group description |
0.9% sodium chloride | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Plasma Purified Alpha-1 antitrypsin (Baseline)
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Reporting group description |
The intervention used was human plasma-purified alpha-1 antitrypsin (Prolastin) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo Arm (Baseline)
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Reporting group description |
0.9% sodium chloride | ||
Reporting group title |
Plasma Purified Alpha-1 antitrypsin (Baseline)
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Reporting group description |
The intervention used was human plasma-purified alpha-1 antitrypsin (Prolastin) | ||
Reporting group title |
Placebo Arm (Day 2)
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Reporting group description |
0.9% sodium chloride | ||
Reporting group title |
Plasma Purified Alpha-1 antitrypsin (Day 2)
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Reporting group description |
The intervention used was human plasma-purified alpha-1 antitrypsin (Prolastin) | ||
Reporting group title |
Placebo Arm (Day 7)
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Reporting group description |
0.9% sodium chloride | ||
Reporting group title |
Plasma Purified Alpha-1 antitrypsin (Day 7)
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Reporting group description |
The intervention used was human plasma-purified alpha-1 antitrypsin (Prolastin) | ||
Reporting group title |
Placebo Arm (Day 28)
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Reporting group description |
0.9% sodium chloride | ||
Reporting group title |
Plasma Purified Alpha-1 antitrypsin (Day 28)
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Reporting group description |
The intervention used was human plasma-purified alpha-1 antitrypsin (Prolastin) | ||
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End point title |
Change in level of circulating IL-6 in plasma at 7 days as measured by ELISA. | ||||||||||||||||||||
End point description |
Plasma was obtained at day 0 and day 7 from patients receiving placebo (n=11) and patients receiving AAT (n=22). IL-6 levels were increased at day 7 compared to day 0 in the placebo group (day 0: 259.9 +/- 206.5 pg/ml, day 7: 348.2 +/- 264.0 pg/ml; P=0.04) and decreased at day 7 in the AAT group (day 0: 296.0 +/- 219.7 pg/ml, day 7: 217.7 +/- 168.7 pg/ml; P=0.003).
The 7-day change in plasma levels of IL-6 from baseline was +88.3 +/- 125.8 pg/ml in the placebo group compared to -78.3 +/- 112.1 pg/ml in the treatment group (P=0.002).
Patients assigned to placebo demonstrated a 37.8+/-56.6% increase in plasma IL-6 at day 7 compared to a mean reduction of 17.4+/-42.3% in those receiving IV AAT (P=0.01). IL = interleukin; AAT = alpha-1 antitrypsin.
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End point type |
Primary
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End point timeframe |
Change from Day 0 to Day 7
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Statistical analysis title |
Statistical analysis of primary endpoint | ||||||||||||||||||||
Statistical analysis description |
Changes in the levels of inflammatory biomarkers within each patient group were analyzed using paired t-tests for normally distributed data and a nonparametric paired Wilcoxon signed-rank test in the event of data failing the test for normality.
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Comparison groups |
Plasma Purified Alpha-1 antitrypsin (Baseline) v Placebo Arm (Baseline)
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Number of subjects included in analysis |
33
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||||||||||
P-value |
< 0.05 [2] | ||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||
Confidence interval |
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Variability estimate |
Standard deviation
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| Notes [1] - Results are reported as absolute numbers or means and standard deviations, as appropriate. Categorical variables are summarized as counts and percentages. No imputation was made for missing data. The primary efficacy analysis was on an intention to treat basis. [2] - Changes in the levels of inflammatory biomarkers within each patient group were analyzed using paired t-tests for normally distributed data and a nonparametric paired Wilcoxon signed-rank test in the event of data failing the test for normality. |
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|||||||||||||||||||||
End point title |
Sequential Organ Failure Assessment (SOFA) score at day 7 | ||||||||||||||||||||
End point description |
Sequential organ failure assessment (SOFA) score, an assessment of clinical severity incritically unwell patients
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline to Day 7
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Circulating AAT levels | ||||||||||||||||||||||||||||
End point description |
Circulating alpha-1 antitrypsin (AAT) levels as measured by nephelometry
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Baseline to Day 7
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Mortality | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured at Day 28
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
ICU Length of Stay | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured at Day 28
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Secondary bacterial pneumonia | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured at Day 28
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Hospital Length of Stay | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
measured at day 28
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Ventilator Free Days | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured at Day 28
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Acute Kidney Injury | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Measured at Day 28
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||
End point title |
PaO2:FIO2 | ||||||||||||||||||||
End point description |
PaO2:FIO2 – ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline to Day 7
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
AEs were checked from the screening period until the Day 28 visit (follow up)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Adverse events were collected by the investigator team through medical chart reviews and discussion with patients at visits where possible.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Human alpha-1 antitrypsin (Prolastin)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
A total of 4 SAEs were recorded in the treatment group, involving 2 patients. Of these, 3 SAEs were deemed not related to the study IMP by the Chief Investigator (CI). One SAE was considered to be possibly related to study IMP by the CI (hypertension persistent for >30 min post-infusion), and resolved without sequelae. None of the SAEs resulted in discontinuation of treatment. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
22 Oct 2020 |
-Estimated trial duration increased to 12 months
-Planned trial sites added
-Addition of new Principal Investigators for this trial
-Removal of wording “patients who are receiving vasopressors (0.05-
0.1μg/kg/min)” when referring to the study population
-Removal of wording “sex & BMI” in randomisation schedule
-Medication administration time changed from 30-45 minutes to approximately 60 minutes
-Inclusion criteria #2 removal of“requirement for vasopressors (0.05- 0.1μg/kg/min)
-Exclusion criteria #5 addition of wording “other than antibiotics or anti- virals”
-Exclusion criteria #19 removed
-Removal of mandatory Isoelectric focusing of plasma to confirm Pi*MM status at screening
-Echocardiogram will be performed at screening only where possible
-Additional notes added:
• The screening visit and baseline visit can occur on the same day
• The follow up visit after Early Discontinuation will be performed as soon as is possible.
• A note added that the most recent results should be documented for assessments performed within 5 days
of the screening visit
-Footnote added to clarify regained capacity consent must be attempted at each visit.
X indicated at Visit 1 & 2 to indicate that family member assent must be attempted before subjects are screened.
-Sections deleted and wording amended to reflect that the Investigators report only serious adverse events that are possibly
related to the study drug
-Planned recruitment rate amended from 2 weeks to 12 months
-Wording amended to interim analysis of cytokine levels taken at 7 days may be conducted. |
||
01 Dec 2020 |
-Addition of Inclusion #4 “Patients receiving invasive mechanical ventilation or non-invasive ventilation”
-Exclusion criteria #1 wording changed from “Not receiving invasive
mechanical ventilation” to “Not receiving invasive mechanical ventilation or non-invasive ventilation” (i.e. patients receiving invasive mechanical ventilation or non-invasive ventilation are eligible for the trial)
-Exclusion criteria #5 wording changed from “Participation in a clinical trial of an investigational medicinal product (other than antibiotics or anti-virals)” to “Participation in a clinical trial of interferon therapies, immune plasma therapies or immunoglobulin within 30 days”
-Exclusion criteria #17 wording changed from “Enrolled in a concomitant clinical trial of a medicinal product (other than antibiotics or anti-virals” to “Enrolled in a concomitant clinical trial of interferon therapies, immune plasma therapies or immunoglobulin” |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The population studied was small which prevented meaningful conclusions regarding clinical outcomes from being drawn. A larger trial is needed to determine the effect of this therapy on clinical outcomes. | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/35291694 |
|||
