Background
In late 2019 novel cases of pneumonia were identified to be a result of a previously unknown type of coronavirus (SARS-CoV2), which causes the disease known as Coronavirus disease 2019 (COVID-19). On January 30, 2020, the outbreak was declared as a Public Health Emergency of International Concern (PHEIC). COVID-19 is an infectious disease capable of person-to-person transmission, and quickly spread worldwide. By the end of March 2020, the mortality rate for hospital admissions in the UK was 5.2% - raising to about 50% for those admitted to an Intensive Care Unit (ICU).
COVID-19 can cause severe pneumonia and multiple organ failure because of the retention of virus-infected, or otherwise activated, macrophages and dendritic cells, which triggers upregulation of inflammation. The severity of the disease is proportional to the amount of cytokines released during inflammation, as the subsequent immune response damages host tissue in the process of targeting the virus.
Given the novelty and severity of COVID-19, in early February, 2020, UK Research and Innovation (UKRI) and the National Institute of Health Research (NIHR) launched a joint strategic initiative to develop understanding, diagnosis, prevention, and treatment of COVID-19.
It is imperative that additional COVID-19 treatments are discovered as fast as possible. One source of potential treatments is drugs (both licenced and unlicensed) that are already designed and available. Some of these drugs have a mechanism of action that has the potential to target the harmful pro-inflammatory response exhibited in COVID-19 patients, thereby allowing for a healthy adaptive immunity to emerge and suppress the viral infection. It is these drugs, alongside other novel therapeutic options, that CATALYST aims to test.
The drugs selected for use in CATALYST are aimed towards patients at risk of deteriorating. These drugs target the middle phase of macrophage activation and prevent the disease from progressing to the stage of organ failure.
About the trial
CATALYST is a rapid, open-label, phase II, a multi-arm multi-stage trial which rapidly tests promising drugs that are currently available, alongside other novel therapeutic options, to assess their safety and potential efficacy. This trial will include hospitalised patients with COVID-19 who are hypoxic, admitted to either hospital wards or ICU, and are at risk of deterioration. Drugs that show promising results will then be considered for larger-scale testing by one of the current national platform trials (RECOVERY or REMAP-CAP). The design of the CATALYST trial is such that new therapies can be introduced sequentially, based on secure laboratory science and clinical outcomes.
Owing to its design and collaboration, CATALYST acts as both a filter and a “spring-board”. It simultaneously discounts unsuitable agents whilst providing promising drugs with a quick and smooth transition into phase III trials. In doing this CATALYST helps meet the need for high-throughput screening (to identify promising COVID-19 treatments), as well as the necessity to get effective treatments to patients as quickly as possible.