Some patients infected with COVID-19 require hospitalisation and develop patients a severe
form of a lung disease called 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, creating a barrier
until the cells regenerate.
In some patients, this clot does not disappear in a timely fashion or interferes with the
development of the new cells. Furthermore, the small clots in the air sacs obstruct the air
and oxygen getting deep into the lungs, interfering with proper ventilation. The trial will
recruit patients with COVID-19 induced ARDS. Eligible patients (or if patients lack capacity,
their legal representative) will be provided with an information sheet and informed consent
will be sought. Eligibility will be mainly assessed via routine clinical assessments.
Patients will receive a nebulised version of a type of drug called tissue plasminogen
activator (rt-PA) that is inhaled using a nebuliser. This is normally a drug used to break
down blood clots. In this situation though, it might be useful for stopping clots forming in
the lungs, because these might lead to even more difficulties with breathing.
The study will run two cohorts sequentially. In cohort 1, 9 consented patients received
nebulised rtPA in addition to SOC. 6 patients were receiving IMV and 3 were receiving non
invasive support with NIV or CPAP or high flow oxygen or standard oxygen therapy. As an
observational arm, matched historical controls who received standard of care were also
recruited at a ratio of 2 controls to every 1 treatment arm patient, resulting in 18
historical controls. Originally, the study aimed to recruit 12 patients with 6 on each
ventilation type (IMV and non-invasive oxygen support). This would have resulted in 24
historical controls. After the first wave of COVID-19 cases decreased in August 2020 in the
UK it became difficult to continue recruitment, so recruitment closed for cohort 1.
With a second surge underway in early 2021, cohort 2 will aim to recruit more patients during
this period to provide more data on the safety of rtPA. Fewer timepoints will be collected,
which will allow for more rapid recruitment while at the same time not compromising safety
monitoring. A more flexible dosing regimen for rtPA will be utilised. 30 patients will be
recruited in total, with an aim to recruit a minimum of 10 IMV patients and 10 patients on
non-invasive oxygen support.
To evaluate efficacy, the improvement of oxygen levels over time and safety will be be
monitored throughout. Blood samples will be taken to measure markers of clotting and
inflammation in both groups.
From the end of the treatment phase both groups will be followed up in accordance with SOC
for 28 days from the day of first dose of rtPA.