OK, we have some more to think about this morning. The large SOLIDARITY trial from the WHO has reported more interim data on its investigation into repurposed drugs for the coronavirus pandemic. And some of this we already knew, but some of it’s a real surprise.
One drug reported on is hydroxychloroquine. This showed no apparent benefit along with a statistical possibility of increased hazard, although the latter was also not proven. This is consistent, as the paper points out, with the results of 27 other trials, and for God’s sake, enough said. Another was the lopinavir/ritonavir combination, and no benefit was found for that, either, which is consistent with two other reported trials. A third intervention was interferon-beta1, with and without lopinavir, but this also showed no evidence of benefit. The statistics on it do not rule out a small useful effect, but do rule out anything moderately beneficial or above, and it’s worth nothing that they don’t rule out small amounts of harm, either. This was either subcutaneous or i.v. administration – there has been a report that administering it to the lungs via a nebulizer could be effective, but that only had 100 patients. There is also another trial underway with s.c. dosing, but after these results it’s hard to be optimistic about that one.
Now we get to remdesivir. In contrast to the report that just came out from the ACTT-1 trial in NEJM, the SOLIDARITY trial found no benefit at all. No benefit in ventilation, in time to recovery, nor in overall mortality. Combining the data from these two reports (and two other smaller controlled Remdesivir trials, the authors conclude:
This absolutely excludes the suggestion that Remdesivir can prevent a substantial fraction of all deaths. The confidence interval is comfortably compatible with prevention of a small fraction of all deaths, but is also comfortably compatible with prevention of no deaths.
Recall that the ACTT-1 trial showed some benefit, but not a dramatic one. These two results are probably not as incompatible as they seem, particularly (as the current paper notes) when you adjust for the fact that in ACTT-1 the randomization put slightly fewer patients on high-flow oxygen or ventilation into its treatment group. So in the same way that I noted that the ACTT-1 data came from a larger set of patients than the earlier remdesivir trials, we have to also deal with the fact that the SOLIDARITY data set is larger still. The authors again:
The unpromising overall findings from the regimens tested suffice to refute early hopes, based on smaller or non-randomized studies, that any will substantially reduce inpatient mortality, initiation of ventilation or hospitalisation duration. Narrower confidence intervals would be helpful (particularly for Remdesivir), but the main need is for better treatments.
I think that’s the major take-home. It looks like there is no case at all to be made for some of these therapies, and for remdesivir, it looks like the argument now is “Does it help a bit or just not at all?” The only thing that I’ve seen that really seems to be making a big difference now is dexamethasone, and we may soon (I hope) be adding the monoclonal antibodies to that list. The SOLIDARITY enrollment is still moving along at 2000 patients/month, and will be looking at these and other newer ideas as it continues. And that means abandoning the older ideas, because – as we’re finding out – they’re not much help. It’s time to move on.
