Acute respiratory distress syndrome (ARDS) caused by COVID-19
Conditions
Interventions
Trade Name: Actilyse
Product Name: Actilyse
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: Alteplase
CAS Number: 0105857-23-6
Concentration unit: mg
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All treatment group patients must meet the following criteria (ward or ICU based): 1. Patients with COVID-19 (confirmed by PCR or radiologically) 2. =16 years 3. Willing and able to provide written informed consent or where patient doesn’t have capacity, consent obtained from a legal representative 4. Patients on IMV must meet both the following criteria: a. PaO2/FiO2 of = 300 b. Intubated > 6 hrs 5. Patients not intubated must meet all the following criteria: a. PaO2/FiO2 = 300 or equivalent imputed by non-linear calculation from SpO2/FiO2 (see look-up table in appendices) b. In-patient >6hours and being actively treated c. On support with non-invasive ventilation OR continuous positive airway pressure (CPAP) OR high flow OR standard oxygen therapy Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: None of the following criteria must apply: 1. Females who are pregnant 2. Concurrent involvement in another experimental investigational medicinal product 3. Known allergies to the IMP or excipients of IMP 4. A pre-existing bleeding disorder with no definitive treatment (e.g. severe haemophilia) 5. Pre-existing severe cardiopulmonary disease (e.g. incurable lung cancer, severe chronic obstructive lung disease, cardiomyopathy, heart failure or impaired contractility <estimated 40% LVEF or RVEF) 6. Fibrinogen < 2.0 g/L at time of screening 7. Patients considered inappropriate for active treatment (e.g. being considered for palliative care) 8. Patients with active bleeding in the preceding 7 days 9. Patients who in the opinion of the investigator are not suitable
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Efficacy - daily during treatment, end of treatment and 3 and 5 days post treatment Safety - every day of trial (and as indicated in each primary outcome measure);Main Objective: 1. Efficacy: Investigate the potential for efficacy of nebulised rtPA in patients presenting with severe COVID-19 requiring IMV or Non-invasive support with NIV OR continuous positive airway pressure (CPAP) OR high flow oxygen Or standard oxygen therapy 2. Safety: Evaluate the safety of nebulised rtPA treatment. ;Secondary Objective: 1. Investigate the impact on patient’s clinical status over time using the WHO ordinal scale of clinical improvement. 2. Investigate the effect of nebulised rtPA on other respiratory markers (such as lung compliance) and organ dysfunction 3. Investigate the impact on in hospital mortality and resource utilisation ;Primary end point(s): Efficacy 1. Change in PaO2/FiO2 ratio from baseline (3 days prior to treatment), daily during treatment, end of treatment and 3 and 5 days post treatment in the groups receiving rtPA Safety 1. Incidence and severity of major bleeding events directly attributable to the study drug 2. Decrease in fibrinogen levels to < 1.5 gm/L during treatment period and 48 hrs after the last dose of treatment 3. Number and nature of serious adverse events causally related to the treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Changes in lung compliance (defined as mL/cm H2O VT / ( PIP – PEEP )) from baseline (3 days prior to treatment) and absolute values at day 5, day 7, end of treatment, 3 days post end of treatment and 5 days post end of treatment 2. Clinical status as assessed by a 7-point WHO ordinal scale at baseline (3 days prior to treatment), daily up to 5 days post end of treatment and at day 28, discharge or death (whichever comes first) 3. Mean daily Sequential Organ Failure Assessment (SOFA) score at baseline (3 days prior to treatment) and daily up to 5 days post end of treatment. 4. In follow up period, number of oxygenation free days, ventilator free days, intensive care stay, up to 28 days or death or discharge, whichever occurs first. 5. Incidence and number of days of new oxygen use, non-invasive ventilation or high flow oxygen devices in the first 28 days. 6. Incidence and number of days of new mechanical ventilation use during in the first 28 days 7. In hospital mortality ;Timepoint(s) of evaluation of this end point: Timepoints for evaluation are as indicated in each secondary endpoint | — |
Countries
United Kingdom
Outcome results
None listed