The newly recognised disease COVID-19 is caused by the Severe-Acute-Respiratory-Syndrome
Coronavirus 2 (SARS-CoV-2), which rapidly spread globally in late 2019, reaching pandemic
proportions. The clinical spectrum of SARS-CoV-2 infection is broad, encompassing
asymptomatic infection, mild upper respiratory tract illness and mild extrapulmonary
symptoms, and severe viral pneumonia with respiratory failure and even death.
For COVID-19, most primary care physicians have initially treated their patients at home
according to their judgment, with various treatment regimens they believe are most
appropriate based on their experience/expertise. We recently published a note on how we were
treating patients at home based on the pathophysiology underlining the mild/moderate symptoms
at the onset of the illness and the proposal of simple drugs that theoretically better fit
these mechanisms.
Because the common early mild symptoms of COVID-19 highlight a systemic inflammatory process,
there is the recommendation of using anti-inflammatory agents to limit excessive host
inflammatory responses to the viral infection, including non-steroidal anti-inflammatory
drugs and corticosteroids. Moreover, COVID-19 patients are exposed to the risk of
thromboembolic events and anticoagulant prophylaxis is recommended even at home, in
particular settings, unless contraindicated.
In an academic matched-cohort study, we found that early treatment of COVID-19 patients at
home by their family doctors according to the proposed recommendation regimen almost
completely prevented the need for hospital admission (the most clinically relevant outcome of
the study along with death) due to progression toward more severe illness (2 out of 90
patients), compared to patients in the 'control' cohort who were treated at home according to
their family physician's assessments (13 out of 90 patients). However, the rate of
hospitalization was a secondary outcome of the study and the possibility of a casual finding
cannot be definitely excluded. Moreover, these findings were achieved in a retrospective
observational study with two matched cohorts of COVID-19 patients, a possible additional
limitation of the robustness of the conclusions that would deserve further validation. Thus,
we have considered the observed reduction in patient hospitalization a hypothesis generating
finding to be confirmed.
In this pragmatic, prospective, three-months, cluster randomized, open-label, blinded
endpoint (PROBE) clinical trial, we will compare two groups of family doctors according to a
randomized approach, who will treat their COVID19-patients with the proposed recommendation
algorithm or other treatment regimens they normally feel appropriate according to their usual
clinical practice, and monitor them longitudinally up to 3 months.
Our working hypothesis is that following the proposed recommendation algorithm the early
COVID-19-related inflammatory process is limited, preventing the need of hospital admission
at larger extent than with other therapeutic approaches also targeting early symptoms of the
illness at home.
Should the findings be confirmed, the tested standardized treatment protocol would achieve
major benefits for patients with early COVID-19 in particular in relation to a remarkably
reduced risk of hospitalization that is expected to translate into reduced morbility and,
possibly, mortality. Notably, these expected clinical benefits would be associated with
remarkably reduced treatment costs related to reduced hospitalization.
Phase:
Phase 3
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research