Page 8 - Palliative Care, Trials and COVID-19 Tribulations: First-hand experience shared by the experts at ground zero

Why Does it Work?

So, why does it work? It actually simplified all the trial procedures. This is because when we
were at the peak of the pandemic, we knew that all the doctors in hospitals were very busy.
We cannot have a very complicated trial procedure. Hence, all the trial procedures were
simplified to be as simple as possible.

Once approval was obtained through the regulatory and ethical board, we used electronic
entry to obtain informed consent from the patients, followed by online randomization. All
done by computer-based. This has cut short a lot of paperwork process.

Unique Clinical Trial

The inclusion criteria are (i) all confirmed COVID-19 patients; (ii) age 18 years and above;
(iii) they must be hospitalized; (iv) able to give consent; (v) not known to receive any of the
study drugs; (vi) without anticipated transfer to elsewhere within 72 hours; (vii) in
physician’s view; there was no contraindication for any study drug.

It included all COVID-19 severity. It can be mild to moderate, or even those patients on
oxygen, inclusive patients on a ventilator except those who are critically ill, the clinicians
thought the patients will not survive in the next 72 hours. The standard of care arm is
according to the local guidelines of each of the countries.

It is very important that each country will have to set its local guidelines because it is the
standard of care arm versus investigational product plus standard of care.

For example, the patients in the standard of care arm, including those on steroids or
Tocilizumab. Then, the patients on an investigational product arm are allowed to receive
steroids or Tocilizumab. This is a special kind of trial design because this is an adaptive trial.
This means that, when we see unpromising drugs, these drugs can be dropped, and other
drugs can be included.

Hydroxychloroquine and Kaletra or Lopinavir/Ritonavir arms were discontinued on the June
20, 2020 and July 14, 2020 respectively because the committee realized that interim analysis
shows futility towards a further development for these two drugs because it did not show any
positive outcomes in the prevention to death or prevention to mechanical ventilator days.
Interferon was later dropped on October 16, 2020. In the end, we are left with Remdesivir
versus standard of care.

Therefore, you can see that in the Solidarity report, the Remdesivir arm actually has over
1,000 patients recruited.