In ourblogfor Clinical Trials Day 2020 we summarized the COVID-19 studies that had been registered so far at theISRCTN registry. One year later and there are now over170COVID-19 studies registered. In this blog we look back at the results of theplatformtrials discussed in our first blog and a selection of therepurposed drug treatmenttrials that have launched since then.
Platform trials
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 course of the trial.
The World Health Organization (WHO) organized the internationalSOLIDARITYtrial and found that treatment regimens with the repurposed antiviral drugs remdesivir, hydroxychloroquine, lopinavir and interferon hadlittle or no effecton hospitalized patients.
RECOVERY
The UK’sRECOVERYtrial isthe world’s largest clinical trialof treatments for COVID-19, with more than 30,000 participants across 177 trial sites at the time of writing. It found that the low-cost steroiddexamethasonereduces mortality by up to one third among hospital patients receiving invasive mechanical ventilation or oxygen.
Preliminary results also showed thattocilizumab(a treatment for rheumatoid arthritis) alsoimproves survival and other clinical outcomes. However, the antiviralslopinavir–ritonavirandhydroxychloroquine, the antibioticazithromycinandconvalescent plasmadid not reduce mortality.The antiviral antibody cocktail REGN-COV2 and the anti-inflammatory drugs aspirin and colchicine have since been added toRECOVERY.
PRINCIPLE
ThePRINCIPLEtrial is testing community treatments for suspected COVID-19 in older people and those with pre-existing conditions at GP practices in England. They are looking for treatments to help people with COVID-19 symptoms recover quickly so that they don’t need to go to hospital.
Hydroxychloroquine was originally included in the trial but was discontinued based on the results of the other studies. The antibioticsazithromycinanddoxycyclinewere also found to be not generally effective.PRINCIPLEis currently testing the commonly-used inhaled corticosteroid budesonide and theanti-inflammatorycolchicine.
Other platform trials
Other platform trials includeACTT-EU/UK, which found thatremdesivirshortened the time to recovery in hospitalized adults.ACCORD-2is testing treatments including bemcentinib, MEDI-3506, acalabrutinib and zilucoplan.
我们当前的知识严重COVID-19建议that the immune system is overactivated in response to the infection, which may lead to organ damage.
我们当前的知识严重COVID-19建议that the immune system is overactivated in response to the infection, which may lead to organ damage. Medications licensed for patients with autoimmune diseases such as rheumatoid arthritis and unlicensed medicines in trials for these conditions are being tested to see if they can prevent this overactivation of the immune response.
The platform trialREMAP-CAPfound that immune modulation withtocilizumab and sarilumabimproved critically ill patients’ outcomes including survival, whileCATALYSTis comparing treatments including the monoclonal antibodies gemtuzumab ozogamicin, namilumab and infliximab to see if they can reduce inflammation in the body caused by the virus.
New trials
Immune modulation
Other monoclonal antibodies being tested include adalimumab, which is being investigated in theAVID-CCtrial to see whether giving it to patients outside hospital can prevent progression to respiratory failure or death.
TACTIC-Ris also recruiting patients at an early stage when they are starting to show mild lung complications to see whether the repurposed drugs ravulizumab and baricitinib can prevent organ damage and reduce the need for ICU treatment and ventilated breathing support.
Otilimab is being tested in theOSCARtrial specifically in patients at a later stage who have developed severe lung complications and require oxygen support or mechanical ventilation.
Antivirals
Several other antiviral drugs are in trials including favipiravir – theGETAFIXstudy is looking at whether giving it to patients with milder COVID-19 symptoms helps with their symptoms and reduces the time it takes to recover.
TheIONICstudy is testing whether a combination of the antiviral oseltamivir and a new medication (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 theSPRINTERtrial to see whether it can accelerate the recovery of hospitalized patients receiving oxygen.
Other repurposed drugs
Other drugs in trials includealmitrine, which is being tested to see if it can improve blood oxygen levels and reduce the need for oxygen therapy and other forms of breathing support. TheRECOVERtrial is investigating whether the blood pressure-lowering drug losartan can improve patient outcomes.
TheILIAD-7-UKtrial aims to find out 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 exhaustion (which prevents the body from dealing with chronic viral infections).
The take-home message
TheISRCTN registrycontinues to support global research on COVID-19 by giving priority to prompt registration and reporting of COVID-19-related studies. All registered studies are made available worldwide through the WHO’sInternational Clinical Trials Registry Platform(ICTRP), and all UK studies appear onBe Part of Research.
In thesecond partof this blog we discussthevaccinetrials and studies looking at testing and the impact of COVID-19 on other conditions.To find out more about how BMC are celebratingClinical Trials Day 2021, please visit ourdedicated page.
Comments