Trial · NCT04356833
Nebulised Rt-PA for ARDS Due to COVID-19
NCT04356833, Phase 2, Completed, University College, London; results first posted 2025-08-11
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Nebulised Rt-PA for ARDS Due to COVID-19. Trials, record NCT04356833. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04356833
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Nebulised Rt-PA for ARDS Due to COVID-19
- NCT number
- NCT04356833
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 35 participants, actual
- Lead sponsor
- University College, London
- Conditions
- COVID
- Interventions
Nebulised recombinant tissue-Plasminogen Activator (rt-PA) - Cohort 1, Nebulised recombinant tissue-Plasminogen Activator (rt-PA) - Cohort 2 IMV, Nebulised recombinant tissue-Plasminogen Activator (rt-PA) - Cohort 2 NIV
- First posted
- 2020-04-22
- Last updated
- 2025-08-11
- Results first posted
- 2025-08-11
- Limitations and caveats
Open label design with a small sample size, missing data and absence of a concurrent control group. A change in a patient's condition could result in an alteration in ventilation type post-enrolment, or in discharge. Furthermore, the P/F ratio was calculated by different methods: for those receiving NIRS, the P/F ratio was determined by converting SpO2 and oxygen flow rate, whereas the P/F ratio was readily available for IMV group.
Source ClinicalTrials.gov
Registered outcomes13
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Efficacy - PaO2/FiO2 Ratio | Day 14 and last value available on treatment (which could occur up to 14 days, death or discharge may have occurred within 14 days) | PaO2/FiO2 measured at multiple timepoints: baseline, during treatment, end of treatment, 3 days post end of treatment and 5 days post end of treatment. For Cohort 1, all available values were extracted per day and summarised every 4 hours (± 2h). For Cohort 2, up to six values were extracted per days including the worst ratio over the preceding day; Cohort 2 included only the lowest value for the day. PaO2/FiO2 ratio is the ratio of arterial oxygen partial pressure to fractional inspired oxygen. It is a widely used clinical indicator of hypoxaemia and is used to classify severity of acute respiratory distress syndrome. Limited data was observed due to patient discharge or death: Day 14 is presented below, and the last value available on treatment regardless of the duration of treatment (death or discharge may have occurred within 14 days) was summarised post-hoc. Summarized values were rounded to the nearest integer. |
| Primary | Safety- Participants With Major Bleeding Events Directly Attributable to Study Drug | 28 days | Number of patients with major bleeding events assessed as related to the study drug summarised in each group. |
| Primary | Safety- Participants With Serious Adverse Events Causally Related to Treatment | 28 days | Number of Participants with serious adverse events causally related to treatment. Adverse events (other than bleeding events) were not recorded in the study. |
| Primary | Safety- Participants With Decrease in Fibrinogen Levels to < 1gm/L | 28 days | Number of participants with a decrease in fibrinogen levels to \< 1gm/L during the treatment period and 48 hours after the last dose. |
| Secondary | Lung Compliance | Last value available on treatment (which could occur up to 14 days, death or discharge may have occurred within 14 days) | Changes in lung compliance (defined as tidal volume / (peak inspiratory pressure - PEEP) from baseline (same day as start of treatment but prior to start of treatment) was a secondary outcome as defined in the protocol. Limited data was observed due to patient discharge or death, therefore the last value available on treatment regardless of the duration of treatment (death or discharge may have occurred within 14 days) was summarised post-hoc and presented below. For cohort 2, the daily measurement coinciding with the worst PF ratio (as close as possible in date and time) was used for the summaries. |
| Secondary | Clinical Status as Determined by a 7-point WHO Ordinal Scale | Day 28 | Clinical status as assessed by a 7-point WHO ordinal scale at baseline and daily up to 5 days post end of treatment and at day 28, discharge or death (whichever comes first). 1. Limitation of activities 2. Hospitalized, no oxygen therapy 3. Oxygen by mask or nasal prongs 4. Non-invasive ventilation or high-flow oxygen 5. Intubation and mechanical ventilation 6. Ventilation+ additional organ support (vasopressor, RRT, ECMO) 7. Death |
| Secondary | Sequential Organ Failure Assessment (SOFA) Score | 28 days (day 14 presented) | The Sequential Organ Failure Assessment (SOFA) is a morbidity severity score and mortality estimation tool developed from a large sample of ICU patients throughout the world. The SOFA was designed to focus on organ dysfunction and morbidity, with less of an emphasis on mortality prediction. It requires the following (worst value within past 24 hours): FiO2, PaO2, Mechanical ventilation, Platelets, Bilirubin, Glasgow coma scale, Mean arterial pressure, Vasopressors, Creatinine, Urine output, and can be calculated by entering the results above into an online tool: https://clincalc.com/IcuMortality/SOFA.aspx. The SOFA Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems. A higher value for each organ system is associated with higher mortality, and here total score was used. The total possible score ranges from 0 to 24. |
| Secondary | Number of Oxygenation Free Days | up to 28 days or death or discharge, whichever occurred first | Number of oxygen free days, up to 28 days or death or discharge, whichever occured first. |
| Secondary | Number of Ventilator Free Days | up to 28 days or death or discharge, whichever occured first | Number of ventilator free days, up to 28 days or death or discharge, whichever occured first |
| Secondary | Intensive Care Stay | 28 days | Intensive care stay, up to 28 days or death or discharge, whichever occurs first, was a secondary outcome as defined in the protocol. However, due to protocol amendments, difficulties in collecting this data, differences in study design between cohort 1 and cohort 2 and limited comparability of this outcome measure between groups, results are presented but have limited interpretation and should not be used or compared. For cohort 1, the number of days in ICU were limited to the 1st admission. |
1 to 10 of 13Source ClinicalTrials.gov
See all 13 registered outcomesOutcomes17
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Efficacy - PaO2/FiO2 Ratio | Day 14 and last value available on treatment (which could occur up to 14 days, death or discharge may have occurred within 14 days) | Limited data was observed due to patient discharge or death: Day 14 is presented below, and the last value available on nebulized Rt-PA treatment regardless of the duration of nebulized Rt-PA treatment (death or discharge may have occurred within 14 days) was summarised post-hoc. The historical matched controls were not treated with nebulized Rt-PA and therefore no data is available in the post-hoc analysis of the last on-treatment day. | mmHg (rounded) | MEAN |
| PRIMARY | Safety- Participants With Major Bleeding Events Directly Attributable to Study Drug | 28 days | Bleeding events were not recorded in historical matched controls (cohort 1) | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | Safety- Participants With Serious Adverse Events Causally Related to Treatment | 28 days | Bleeding events were not recorded in historical matched controls (cohort 1) Adverse events (other than bleeding events) were not recorded in the study | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | Safety- Participants With Decrease in Fibrinogen Levels to < 1gm/L | 28 days | Fibrinogen levels were not recorded for the historical matched controls (cohort 1) | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Lung Compliance | Last value available on treatment (which could occur up to 14 days, death or discharge may have occurred within 14 days) | Lung compliance was not recorded in the historical matched controls (cohort 1) or in patients in the NIV group. During the COVID pandemic, investigations and observations were done less rigorously than compared to routine care. Many of the secondary outcome measures were based on the standard of care rather than being study specific observations. | mL/cmH2O | MEAN |
| SECONDARY | Clinical Status as Determined by a 7-point WHO Ordinal Scale | Day 28 | This outcome measure was modified between cohort 1 and 2, and the 7-point WHO scale was only collected from patients in cohort 2. Limited data was observed due to patient discharge or death, therefore only data for cohort 2 are presented. During the COVID pandemic, investigations and observations were done less rigorously than compared to routine care. Many of the secondary outcome measures were based on the standard of care rather than being study specific observations. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Sequential Organ Failure Assessment (SOFA) Score | 28 days (day 14 presented) | During the COVID pandemic, investigations and observations were done less rigorously than compared to routine care. Many of the secondary outcome measures were based on the standard of care rather than being study specific observations. | score on a scale | MEAN |
| SECONDARY | Number of Oxygenation Free Days | up to 28 days or death or discharge, whichever occurred first | days | MEDIAN | |
| SECONDARY | Number of Ventilator Free Days | up to 28 days or death or discharge, whichever occured first | Days | MEDIAN | |
| SECONDARY | Intensive Care Stay | 28 days | Due to protocol amendments, difficulties in collecting this data (owing to a combination of death, recovery and a smaller data set used for monitoring patients during COVID), differences in study design between cohort 1 \& cohort 2, and limited comparability of this outcome measure between groups, results are presented but have limited interpretation and should not be used or compared. For cohort 1, the number of days in ICU were limited to the 1st admission. | Days | MEDIAN |
1 to 10 of 17Source ClinicalTrials.gov
See all 17 outcomesResults by group76
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Efficacy - PaO2/FiO2 Ratio | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | Day 14 | 227 | Standard Deviation 83 | mmHg (rounded) |
| Efficacy - PaO2/FiO2 Ratio | Historical Matched Controls - Cohort 1 | Day 14 | 209 | Standard Deviation 49 | mmHg (rounded) |
| Efficacy - PaO2/FiO2 Ratio | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 IMV | Day 14 | 155 | Standard Deviation 104 | mmHg (rounded) |
| Efficacy - PaO2/FiO2 Ratio | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 NIV | Day 14 | 248 | Standard Deviation 89 | mmHg (rounded) |
| Efficacy - PaO2/FiO2 Ratio | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | Last On-Treatment Day | 218 | Standard Deviation 73 | mmHg (rounded) |
| Efficacy - PaO2/FiO2 Ratio | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 IMV | Last On-Treatment Day | 169 | Standard Deviation 108 | mmHg (rounded) |
| Efficacy - PaO2/FiO2 Ratio | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 NIV | Last On-Treatment Day | 240 | Standard Deviation 104 | mmHg (rounded) |
| Safety- Participants With Major Bleeding Events Directly Attributable to Study Drug | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | 0 | Participants | ||
| Safety- Participants With Major Bleeding Events Directly Attributable to Study Drug | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 IMV | 1 | Participants | ||
| Safety- Participants With Major Bleeding Events Directly Attributable to Study Drug | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 NIV | 0 | Participants |
1 to 10 of 76Source ClinicalTrials.gov
See all 76 results by groupParticipant flow12
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | 9 | |
| Overall Study | STARTED | Historical Matched Controls - Cohort 1 | 18 | |
| Overall Study | STARTED | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 IMV Arm | 12 | |
| Overall Study | STARTED | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 NIV Arm | 14 | |
| Overall Study | COMPLETED | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | 9 | |
| Overall Study | COMPLETED | Historical Matched Controls - Cohort 1 | 18 | |
| Overall Study | COMPLETED | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 IMV Arm | 12 | |
| Overall Study | COMPLETED | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 NIV Arm | 14 | |
| Overall Study | NOT COMPLETED | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | 0 | |
| Overall Study | NOT COMPLETED | Historical Matched Controls - Cohort 1 | 0 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 participant flowAdverse events32
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Bleed: Central venous catheters access site | Surgical and medical procedures | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | 2 | 9 | 2 |
| other | Bleed: Central venous catheters access site | Surgical and medical procedures | Historical Matched Controls - Cohort 1 | 0 | 0 | 0 |
| other | Bleed: Central venous catheters access site | Surgical and medical procedures | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 IMV | 0 | 12 | 0 |
| other | Bleed: Central venous catheters access site | Surgical and medical procedures | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 NIV | 0 | 14 | 0 |
| other | Gastro-intestinal bleed | Gastrointestinal disorders | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | 1 | 9 | 1 |
| other | Gastro-intestinal bleed | Gastrointestinal disorders | Historical Matched Controls - Cohort 1 | 0 | 0 | 0 |
| other | Gastro-intestinal bleed | Gastrointestinal disorders | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 IMV | 0 | 12 | 0 |
| other | Gastro-intestinal bleed | Gastrointestinal disorders | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 NIV | 2 | 14 | 2 |
| other | Blood-stained tracheobronchial secretion | Surgical and medical procedures | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | 1 | 9 | 1 |
| other | Blood-stained tracheobronchial secretion | Surgical and medical procedures | Historical Matched Controls - Cohort 1 | 0 | 0 | 0 |
1 to 10 of 32Source ClinicalTrials.gov
See all 32 adverse eventsAdverse event totals12
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | 1 | 9 |
| Total, all-cause mortality | Historical Matched Controls - Cohort 1 | 10 | 18 |
| Total, all-cause mortality | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 IMV | 5 | 12 |
| Total, all-cause mortality | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 NIV | 3 | 14 |
| Total, other adverse events | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | 4 | 9 |
| Total, other adverse events | Historical Matched Controls - Cohort 1 | 0 | 0 |
| Total, other adverse events | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 IMV | 9 | 12 |
| Total, other adverse events | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 2 NIV | 4 | 14 |
| Total, serious adverse events | Nebulised Recombinant Tissue-Plasminogen Activator (Rt-PA) - Cohort 1 | 0 | 9 |
| Total, serious adverse events | Historical Matched Controls - Cohort 1 | 0 | 0 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse event totalsPapers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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