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Alpha blockers associated with >50% reduction in mortality in our retrospective study

(Joshua Vogelstein) #1

hi OHDSI - i wanted to bring to your attention our pre-print:

I am very new to observational health data, and OHDSI,
several members of OHDSI have been kind enough to provide us with some guidance,
including @msuchard @aki-nishimura.
our study protocol continues to improve, to bring it up to OHDSI standards.
as it stands, our retrospective analysis has been sufficient to:

  1. lead to johns hopkins (#1 hospital in the world) start a clinical inpatient trial using alpha blockers, the first trial approved at JHH
  2. get FDA approval to run a multi-center trial

BUT, we don’t have any evidence from COVID patients yet,
and we have a study that could be improved and scaled by this community even in pneumonia and acute respiratory success.
we have been fortunate enough to raise money to support these efforts,
so we are now actively looking for partners in both the COVID data analysis plan/implementation,
and the actual clinical trial partnerships.

we are also talking with a number of other funders, pharma, etc., and getting more support/encouragement as existing potential remedies seem to be falling.

If anybody is interested, please let me know.

many thanks for all your guidance, openness, and leadership throughout this crisis.

(Robert Clark) #2

Thanks for that. I’m very interested in using statistical analysis to find effective drugs against COVID-19.

By the way, why did you choose to publish this on arxiv.org instead of medrxiv.org? The latter is reviewed by large numbers of people both in the medical field and not in regards to COVID-19, so your study would have gotten much more notice if it had been on medrxiv.org

Robert Clark

(Joshua Vogelstein) #3

hey @Robert_Clark fun to talk to you on multiple threads :slight_smile:
for reference, the following links are live, all of which we thought would have gotten some notice:

  1. Published a peer-reviewed article in Journal of Clinical Investigations discussing our idea for using alpha-blockers prophylactically based on the preclinical data, Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists.
  2. We actually posted a pre-print of that work on medRxiv, as you suggested, but JCI required that we removed the data, so we had to write another paper just on the data. medRxiv was taking 8 days to post or update, so we decided to put the next one on arxiv to reach a broader audience.
  3. The arxiv paper shows a retrospective analysis on patients with pneumonia and acute respiratory distress, indicating a reduction in mortality of >50% for people prophylactically taking alpha blockers, Alpha-1 adrenergic receptor antagonists prevent acute respiratory distress syndrome and death: implications for Coronavirus disease 2019.
  4. FDA and the IRB at Johns Hopkins have approved our inpatient clinical trial, which is poised to begin this week, Prazosin to Prevent COVID-19 (PREVENT-COVID Trial).
  5. Popular press articles in Forbes (Prazosin Might Be A Treatment For COVID-19. More Data Is Urgently Needed), and The Atlantic (Why COVID-19 Makes Some People Sicker Than Others) were written as well.

If you have other ideas for how to get more notice, we’d love to hear them.
We are, however, being very careful as to not put any information outside technical formats, because we are concerned about the public misunderstanding; we need clinical trials to get safety confirmation in COVID patient populations, and we do not want people starting regiments outside clinical trials.
So it is a fine balance of trying to tell clinicians, scientists, and other stakeholders, while avoiding what happened with HCQ, and is potentially happening now with Remdesivir.

(Robert Clark) #4

Thanks for the response. I couldn’t get the full version of the report, “Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists” to open. Perhaps it is still in review.

Robert Clark

(Joshua Vogelstein) #5

interesting, i just tried and it works for me.
i’m guessing sci-hub could help, though it is an open access manuscript.
it is still “in press”, so you have to explicitly download the pdf.
review and proofs are both done.