I just saw this thread by @MarkHoofnagle and feel compelled to respond to clarify some things.
Disclaimers: I am not an ID expert. I am a Medical Intensivist in the Military. These are not the official views of the DoD. Just my personal opinions. No financial COIs.
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Disclaimers: I am not an ID expert. I am a Medical Intensivist in the Military. These are not the official views of the DoD. Just my personal opinions. No financial COIs.
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I have participated only as a site-AI but I have participated in investigator meetings since the inception of this trial so I have *some* inside knowledge.
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First off, this trial was conceived and protocol approved before our very first US case back in February. It is funded by NIAID. Not Gilead. Remdesivir was chosen because of its potential. Not financially motivated.
Full info here. 👇
clinicaltrials.gov/ct2/show/NCT04…
Full info here. 👇
clinicaltrials.gov/ct2/show/NCT04…
The early findings released this week were *preliminary*. Only 400 of the over 1000 subjects have complete data to analyze. This was an interim analysis by the DSMB to help inform the next trial. Results like these are typically not released. But these are not normal times...
Info about what was released...
Yes the Primary endpoint was changed. However, mortality was always a SECONDARY endpoint. The original primary endpoint was a complicated 8 point ordinal scale. It was merely simplified.
History of changes here. 👇
clinicaltrials.gov/ct2/history/NC…
History of changes here. 👇
clinicaltrials.gov/ct2/history/NC…
From this...
The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen;
The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen;
5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Complicated right?
Complicated right?
To this...3 point ordinal scale.
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale:
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale:
1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
@MarkHoofnagle makes an excellent point about viral replication in influenza peaks early.
This are a lot of unknowns for #COVID19. We don't even have a reliable test to look at this yet. Viral RNA is present in high quantities. But not a good way to measure viral load.
This are a lot of unknowns for #COVID19. We don't even have a reliable test to look at this yet. Viral RNA is present in high quantities. But not a good way to measure viral load.
If you assume that presence of viral RNA=viral load then it appears nCoV is more like MERS. Sick patients have evidence of high viral RNA into the second week.
nejm.org/doi/full/10.10…
nejm.org/doi/full/10.10…
As @MarkHoofnagle points out, the Chinese RCT in Lancet did not show a difference in viral RNA between Remdesivir or placebo. This was surprising. But these were NP samples. What's happening in the lung? Or anywhere else? All unknowns... 
The interim analysis was a first step. Showed a positive signal in a trial that is scientifically sound and completely transparent. Tells us that there is a big enough difference between the 2 groups that the next trial should not include a placebo arm.
It will be Remdesivir vs Remdesivir+immune modifying agent. Better than the multiple arms the study would need if there was not difference detected at all.
Is Remdesivir a cure? No. It is not. It is a great first step in the data free wild west we've all been practicing in.
Should you use Remdesivir in your patients? That's your call as the treating physician after weighing risk/benefit, data to date, and talking to your Pt.
Should you use Remdesivir in your patients? That's your call as the treating physician after weighing risk/benefit, data to date, and talking to your Pt.
Let's wait though until the peer reviewed data comes out for all to scrutinize before making absolute statements one way or another.
The NIAID team (and collaborators) are working their tails off to deliver some hope to our community and our patients.
The NIAID team (and collaborators) are working their tails off to deliver some hope to our community and our patients.
To clarify...presence of viral RNA does not necessarily mean you have active functionally active virus. Absence of RNA somewhere doesn’t rule out presence of active virus somewhere else either. Lots of unknowns.
