The SARS-CoV-2 virus
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In our Blog For Clinical Trials Day 2020, we summarized the COVID-19 studies that had been recorded so far at ISRCTN Registry. A year later and there are now more 170 COVID-19 studies recorded. In this blog, we review the results of Platform essays discussed in our first blog and a selection of drug treatment reused tests launched since.
Platform trials compare multiple treatments at the same time using a single protocol, allowing new treatments to be added and ineffective treatments to be dropped throughout the trial.
The World Health Organization (WHO) organized the SOLIDARITY and found that treatment regimens with the reused antiviral drugs remdesivir, hydroxychloroquine, lopinavir and interferon had little or no effect on hospitalized patients.
The United Kingdom RECOVERY the trial is the largest clinical trial in the world treatments for COVID-19, with more than 30,000 participants at 177 trial sites at the time of writing. He found that the low cost steroid dexamethasone reduces mortality by up to a third in hospitalized patients receiving invasive mechanical ventilation or oxygen.
Preliminary results also showed that tocilizumab (a treatment for rheumatoid arthritis) too improves survival and other clinical outcomes. However, antivirals lopinavir – ritonavir and hydroxychloroquine, the antibiotic azithromycin and convalescent plasma did not reduce mortality. The cocktail of antiviral antibodies REGN-COV2 and the anti-inflammatory drugs aspirin and colchicine have since been added to RECOVERY.
the PRINCIPLE The trial is testing community-based treatments for suspected COVID-19 in the elderly and those with pre-existing conditions in GP practices in England. They are looking for treatments to help people with symptoms of COVID-19 recover quickly so they don’t need to go to the hospital.
Hydroxychloroquine was initially included in the trial but was discontinued based on the results of the other studies. Antibiotics azithromycin and doxycycline have also been found to be generally ineffective. PRINCIPLE is currently testing the commonly used inhaled corticosteroid budesonide and anti-inflammatory colchicine.
Other platform tests
Other platform tests include ACTT-EU / United Kingdom, who found that remdesivir shortened recovery time in hospitalized adults. AGREEMENT-2 is testing treatments including bemcentinib, MEDI-3506, acalabrutinib and zilucoplan.
Our current knowledge of severe COVID-19 suggests that the immune system is overactivated in response to infection, which can lead to organ damage.
Our current knowledge of severe COVID-19 suggests that the immune system is overactivated in response to infection, which can lead to organ damage. Drugs approved for patients with autoimmune diseases such as rheumatoid arthritis and drugs not approved in trials for these conditions are being tested to see if they can prevent this overactivation of the immune response.
Testing the platform REMAP-CAP found that immune modulation with tocilizumab and sarilumab improved critically ill patient outcomes, including survival, while CATALYST is comparing treatments including monoclonal antibodies gemtuzumab ozogamicin, namilumab and infliximab to see if they can reduce inflammation in the body caused by the virus.
Other monoclonal antibodies tested include adalimumab, which is currently the subject of AVID-CC testing to see if giving it to patients outside the hospital can prevent progression to respiratory failure or death.
TACTIC-R also recruits patients at an early stage when they begin to have mild pulmonary complications to see if the reused drugs ravulizumab and baricitinib can prevent organ damage and reduce the need for intensive care unit treatment and ventilated respiratory support .
Otilimab is tested in the OSCAR test specifically in patients at a later stage who have developed severe pulmonary complications and require oxygen or mechanical ventilation.
Several other antiviral drugs are being tested, including favipiravir – the GETAFIX The study is investigating whether giving it to patients with milder symptoms of COVID-19 helps alleviate their symptoms and shortens the time it takes to recover.
the IONIC A study is testing whether a combination of the antiviral oseltamivir and a new drug (IMU-838) can improve the time it takes to recover from COVID-19. SNG001, an inhaled drug that contains the antiviral protein interferon-β, is being tested in the SPRINTER test to see if it can speed recovery for hospital patients receiving oxygen.
Other reused drugs
Other drugs being tested include almitrine, which is being tested to see if it can improve blood oxygen levels and reduce the need for oxygen therapy and other forms of respiratory support. the RECOVER The trial is investigating whether losartan, an antihypertensive drug, can improve patient outcomes.
the ILIAD-7-UK The trial aims to determine whether the drug CYT107 can reduce mortality by reversing lymphopenia (where patients have abnormally low levels of white blood cells called lymphocytes) and T cell depletion (which prevents the body from dealing with infections. chronic viral infections).
Take home message
the ISRCTN Registry continues to support global research on COVID-19 by prioritizing the timely registration and notification of studies related to COVID-19. All recorded studies are made available worldwide through the International clinical trials registration platform (ICTRP), and all UK studies appear on Be part of the research.
In the second part from this blog we discuss the vaccine trials and studies examining the testing and impact of COVID-19 on other conditions.