April 23, 2020

expert reaction to study looking at the drugs lopinavir/ritonavir or arbidol to treat-to-moderate COVID-19 in adults

A study, published in the journal Cell Med, reports on the drugs lopinavir/ritonavir or arbidol to treat-to-moderate COVID-19 in adults.

Prof Duncan Richards, Clinical Pharmacologist and CLIMAX Professor of Clinical Therapeutics, University of Oxford, said:

“Pilot studies have an important role to identify those treatments with some potential which should then be studied in large studies. These pilot studies can only detect large treatment differences or safety signals. In this case the sample size was based on how many people came into the hospital. This is not an appropriate approach, even when one does not have prior data to accurately size the study one should make an assessment of the treatment effect you can detect. In this case there is already another larger pilot study published in the NEJM (Cao et al) for Lopinavir/ritonavir, this did not meet its primary endpoint but showed some promise on secondary endpoints. In this setting multiple pilots are no substitute for one larger study.

“Lopinavir/ritonavir is now being assessed in a large outcomes study RECOVERY (7000 participants recruited) in the UK. This will give us an answer. Multiple unpowered pilot studies will tell us little.”

Prof Ian Jones, Professor of Virology, University of Reading, said:

“We are beginning to see a number of early drug trial reports and, generally, the results are disappointing. In this case the drugs were a long shot as they were developed for different viruses, not specifically for coronaviruses. But it should also be borne in mind that, for drugs that target the virus itself, the timing of any drug treatment is crucial. Antivirals have to be given as early as possible if their effect on the virus is to have any clinical effect. Think “bull in a china shop”, if the bull is stopped as it leaves the shop the damage is already done but if it is stopped soon after entry, the damage is much reduced. Ideally drug treatment would follow an early diagnosis when symptoms are hardly present. So it is too early to give up on Covid drug therapy yet. Given at the appropriate time they could still impact disease, improve recovery and limit virus spread. More trials, with drug given at earlier times, are needed.”

Dr James Gill, Honorary Clinical Lecturer, Warwick Medical School, and Locum GP, said:

“Whilst the labs of the world are working on vaccine candidates to help overcome the COVID-19 pandemic tomorrow, the clinicians of the world are looking to their drug books and research pharmaceuticals  to find medications which may support patients who are ill with COVID-19 today.

“The Cell Med journal has just released reports of the failure of two therapeutic options Lopinavir/ritonavir and Arbidol to aid those with mild to moderate COVID-19 symptoms. 

“Why can this lack of success considered a positive? Currently we have few treatments to support patients, as a result we are desperately testing multiple options. Whilst multiple options gives the potential of benefit, it also give the potential for side effects, and possible patient harm 

“By being able to rule out Lopinavir/ritonavir and Arbidol from contention for COVID-19 treatments, it allows medics and scientists to focus on other potential hopes of treatment options 

“Whilst positive news would be preferable. Definitive information is always a good step in building our knowledge to combat COVID-19 and protect patients from iatrogenic harm.” 

“Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial” by Yueping Li et al. was published in Cell Med

https://marlin-prod.literatumonline.com/pb-assets/products/coronavirus/MEDJ1.pdf

All our previous output on this subject can be seen at this weblink: www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Ian Jones: No conflicts

None others received.