Phase 2 N=53 Treatment

Nebulised Rt-PA for ARDS Due to COVID-19

COVID

Bottom Line

View on ClinicalTrials.gov: NCT04356833 ↗

Enrolled (actual)

Serious AEs

2.9%

Results posted

Aug 2025

Primary outcome: Primary: Efficacy - PaO2/FiO2 Ratio — 227; 209; 155; 248 mmHg (rounded)

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Nebulised recombinant tissue-Plasminogen Activator (rt-PA) - Cohort 1 (Drug); Nebulised recombinant tissue-Plasminogen Activator (rt-PA) - Cohort 2 IMV (Drug); Nebulised recombinant tissue-Plasminogen Activator (rt-PA) - Cohort 2 NIV (Drug)
Age: Pediatric, Adult, Older Adult · 16+ yrs
Sex: All
Sponsor: University College, London
Primary completion: Mar 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Efficacy - PaO2/FiO2 Ratio	227; 209; 155; 248; 218; 169	—
PRIMARY Safety- Participants With Major Bleeding Events Directly Attributable to Study Drug	0; 1; 0	—
PRIMARY Safety- Participants With Serious Adverse Events Causally Related to Treatment	0; 0; 0	—
PRIMARY Safety- Participants With Decrease in Fibrinogen Levels to < 1gm/L	0; 0; 0	—
SECONDARY Lung Compliance	40.4; 37.6	—
SECONDARY Clinical Status as Determined by a 7-point WHO Ordinal Scale	0; 0; 0; 0; 1; 2	—
SECONDARY Sequential Organ Failure Assessment (SOFA) Score	7.71; 7; 10.7; 4.8	—
SECONDARY Number of Oxygenation Free Days	0; 0.5; 0; 0	—
SECONDARY Number of Ventilator Free Days	0; 7.5; 0; 1.5	—
SECONDARY Intensive Care Stay	19; 12; 9; 5	—
SECONDARY Number of Days of New Mechanical Ventilation Use During in the First 28 Days	14.5; 0; 23; 10.5	—
SECONDARY Number of Days of Non-invasive Ventilation Use	0.5; 6; 6.5; 3	—
SECONDARY In-hospital Mortality	1; 10; 5; 3	—

Summary

Some patients infected with COVID-19 develop a severe form of a lung disease called acute respiratory distress syndrome (ARDS). In these patients, the lungs become severely inflamed because of the virus. The inflammation causes fluid from nearby blood vessels to leak into the tiny air sacs in the lungs, making breathing increasingly difficult. This fluid forms small clots in the air sacs. In some patients, these clots do not disappear in a timely fashion. Furthermore, the small clots in the air sacs obstruct the air and oxygen getting deep into the lungs, interfering with ventilation. The trial recruited patients with COVID-19 induced ARDS. Eligible patients (or if patients lack capacity, their legal representative) were provided with an information sheet and informed consent was sought. Eligibility was mainly assessed via routine clinical assessments. Patients received a nebulised version of a type of drug called tissue plasminogen activator (rt-PA) that was inhaled using a nebuliser. This is normally a drug used to break down blood clots. In the nebulised form, we hypothesised that it may be useful for stopping clots forming in the lungs. The study ran two cohorts sequentially. In cohort 1, 9 consented patients received nebulised rtPA in addition to SOC. As an observational arm, matched historical controls who received SOC were also recruited at a ratio of 2 controls to every 1 treatment arm patient, resulting in 18 historical controls. After the first wave of COVID-19 cases decreased in August 2020 in the UK, it became difficult to continue recruiting, so recruitment was closed for cohort 1. With a second surge in early 2021, cohort 2 opened with the aim to recruit more patients to provide more data on the safety of rt-PA. In cohort 2, fewer timepoints were collected, which allowed for more rapid recruitment without compromising safety monitoring. A more flexible dosing regimen for rtPA was utilised. 26 patients were recruited in total, 12 in the IMV arm and 14 in the NIV/NIRS arm. To evaluate drug efficacy, the improvement of oxygen levels over time and safety were monitored throughout. Blood samples were taken to measure markers of clotting and inflammation in both cohorts. From the end of the treatment phase, both groups were followed up in accordance with SOC up to a maximum of 28 days, starting from the day of first dose of rt-PA.

Eligibility Criteria

Inclusion Criteria (cohorts 1 and 2):

Patients with COVID-19 (confirmed by PCR or radiologically)
≥16 years
Willing and able to provide written informed consent or where patient doesn't have capacity, consent obtained from a legal representative
Patients on IMV must meet both the following criteria:
PaO2/FiO2 of ≤ 300 (definition of ARDS)
Intubated > 6 hrs
Patients not intubated must meet the following criteria:
PaO2/FiO2 ≤ 300 or equivalent imputed by non-linear calculation from SpO2/FiO2 (see look-up table in appendices)
In-patient >6 hours and being actively treated
On support with non-invasive ventilation OR continuous positive airway pressure (CPAP) OR high flow OR standard oxygen therapy

Exclusion Criteria (cohort 1):

Females who are pregnant
Concurrent involvement in another experimental investigational medicinal product
Known allergies to the IMP or excipients of IMP
A pre-existing bleeding disorder (e.g. severe haemophilia) with no definitive treatment
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)
Fibrinogen < 2.0 g/L at time of screening
Patients considered inappropriate for active treatment (e.g. being considered for palliative care)
Patients with active bleeding in the preceding 7 days
Patients who in the opinion of the investigator are not suitable

Exclusion Criteria (cohort 2):

Females who are pregnant
Known allergies to the IMP or excipients of IMP
Fibrinogen < 1.5 g/L at time of screening
Patients considered inappropriate for active treatment (e.g. being considered for palliative care)
Patients who in the opinion of the investigator are not suitable

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04356833). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.