E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Compare reduction in inflammatory markers between PEX and a control group in patients with severe COVID |
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E.2.2 | Secondary objectives of the trial |
Among patients requiring CPAP/ NIV at treatment onset, the ability to prevent deterioration to requiring mechanical ventilation
Reduction in clinical thrombotic events documented by DVT, or arterial thrombus (cardiac, neurological and peripheral vascular)
Reduction in the inflammatory-thrombotic response by monitoring VWFAg/ADAMTS 13 activity ratio by 50% from baseline pre PEX to the end of treatment.
Stable cardiac function throughout period of PEX based on echocardiogram/troponin/BNP measurements
28 day mortality
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 18-70 • Proven Covid-19/high clinical suspicion of Covid-19 • Hypoxia/respiratory compromise defined as requiring respiratory support of >2L/min of oxygen by nasal cannulae to maintain SpO2<96%. • Raised inflammatory parameters: at least 2 of the following: a. Raised LDH (> 2 x ULN) b. Raised D Dimers (> 2X ULN) c. Raised CRP (>2X ULN)
• Females of childbearing potential have a negative pregnancy test within 7 days prior to being randomised. Participants are considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
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E.4 | Principal exclusion criteria |
• Significant co-morbid illness with treatment escalation limited to CPAP • Active bleeding • PF ratio < 100 on mechanical ventilation OR noradrenaline requirement > 0.5mcg/kg/min to maintain MAP > 65mmHg (suggests futility) • Pregnancy • Known allergies to Octaplas or excipients |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the reduction in inflammatory markers between Plasma Exchange (PEX) and the control group in patients with severe COVID |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
These parameters will be analysed at the beginning of the trial to assess eligibility and at the end when all the data has been collected |
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E.5.2 | Secondary end point(s) |
Primary: To compare the reduction in inflammatory markers between Plasma Exchange (PEX) and the control group in patients with severe COVID Secondary: To compare rates of mechanical ventilation between Plasma Exchange (PEX) and control groups in patients with severe COVID requiring CPAP/ NIV at treatment onset
To compare rates of clinical thrombotic events either venous (deep vein thrombosis DVT or pulmonary embolism PE) or arterial thrombus (cardiac, neurological and peripheral vascular) between Plasma Exchange (PEX) and control groups in patients with severe COVID
To compare reduction in the inflammatory-thrombotic response by monitoring von Willebrand factor VWFA antigen/ADAMTS 13 activity ratio between Plasma Exchange (PEX) and control groups in patients with severe COVID
To compare the stability of cardiac function based on echocardiogram/troponin/BNP measurements cardiac function between Plasma Exchange (PEX) and control groups in patients with severe COVID
To compare incidence of acute kidney injury as defined by KDIGO criteria between Plasma Exchange (PEX) and control groups in patients with severe COVID
To compare mortality at day 28 between the PEX and control groups
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
These parameters will be analysed at the beginning of the trial to assess eligibility and at the end when all the data has been collected |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 14 |