This first post was published on 4/4/2020 regarding hydroxychloroquine and azithromycin in COVID patients. Other studies will be noted by dates below. I decided to consolidate multiple posts into one for the sake of simplicity.
For those of you new to the page/blog, I am a Critical Care physician. My team and I are usually the last line of care patients receive. Many of you are part of my extended team working in ICU’s throughout the world. I would honestly love for this combination of HCQ and azithro to work. This study makes us further curb our enthusiasm.
A bit of background:
The two French studies that “showed a benefit” as well as the Chinese study I posted that “showed a benefit” were conducted in patients who were NOT critically ill. This paper was published on March 30th. I’m late to the party, I know. But it correlates with the anecdotal experience I’ve noted from various facilities who are taking care of critically ill patients.
We get another small study here. n=11. They weren’t critically ill when they started the data collection but within 5 days, 1 died and 2 were transferred to the ICU.
Regimen: HCQ 600mg daily x 10 days + Azithromycin 500mg on day 1, 250mg on days 2-5.
Results: 8 patients still had positive RNA at days 5 to 6 after treatment initiation.
Bottom line: in this subset of patients, there was no rapid clearance of COVID-19 by giving this combination. It wasn’t as 100% as the Gautret/Raoult studies that I have taken apart in the past. This study is also fraught with flaws. No control group, small, no baseline characteristics. They do not define what made these patients “severe” as opposed to mild or moderate. They could have also waited the full 10 days of therapy. I guess they were in a rush to pump out data or they’re going to publish the full data in a couple days and have two publications for their CV instead of just one. Sigh.
I am personally not excited about the HCQ/Azithro combo in my critically ill patients.
Click here for breakdowns of other COVID-19 Articles.
Citation 1
Molina JM, Delaugerre C, Goff JL, Mela-Lima B, Ponscarme D, Goldwirt L, de Castro N, No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection, Me ́decine et Maladies Infectieuses (2020), doi: https://doi.org/10.1016/j.medmal.2020.03.006
Link to Abstract
Link to FULL FREE PDF
Hydroxychloroquine for COVID-19: Not A Peer Reviewed Study
The following post was from 3/31/2020.
This is some actual data regarding the effects of hydroxychloroquine in COVID-19! A hat tip to the authors. This is not the most robust study with the most conventional endpoints but it’s something. It is very small but I’d rather it exist than not exist at this juncture. These patients are not ICU level patients.
Disclaimer: this is a not a peer reviewed article at the time of my writing. This is also my interpretation of the study.
The authors wanted to see the effects of hydroxychloroquine in patients with COVID-19. No azithro was harmed in this study that I can tell.
n=62, RCT
31 received standard treatment PLUS a 5 days course of HCQ 400mg daily
Mean age: 44.7 (not the oldest folks, older tend to be sicker.)
All 62 patients also received antivirals, antibiotics (zero mentions of azithro in the article), immunoglobulins +/- steroids.
Noteworthy excluded patients (cannot discuss all of these): severe and critically ill patients. Renal failure. Others. Bottom line is that these patients are not SICK SICK SICK.
There’s no subgroup analysis to see how the +/- steroids may have influenced the results.
Endpoints and Results (assessed at baseline and after 5 days of treatment)
Time to clinical recovery: body temperature, cough remission time. Fewer patients in the control group had fevers, despite this, fever resolved quicker in the HCQ group. Fewer patients had cough in the control group. Also despite this, fewer patients had cough in the HCQ group. Bottom line, patients with HCQ felt better. This is a strange endpoint.
Radiological results: CT scan on day 0 and on day 6. Improved pneumonia in 80.6% of HCQ arm versus 54.8% in the control arm. NNT=3.9. 61.3% of the patients in the HCQ group had a significant absorption of their pneumonia.
4 patients progressed to severe illness in the control group. That’s almost 13% of the group. None in HCQ group.
Adverse reactions:
In the HCQ group, one patient had a rash, another had a headache.
Conclusions:
The authors concluded that HCQ could shorten the time to clinical recovery and promote the absorption of pneumonia. The mechanisms by which this occurs are postulated in the article. This would support giving HCQ to patients who are not critically ill as we do not know its effects on that population, yet.
Citation
Link to FULL FREE Article
Link to Abstract
Hydroxychloroquine & Azithromycin for COVID-19: The Study Published on 3/27/20
We have an update now from the same researchers in France regarding hydroxychloroquine and azithromycin in COVID-19. It’s a free PDF and I recommend you read it yourself. Don’t trust me.
This study has me scratching my head. Their first study seemed like they rushed it out the door to light the fire for some more research. This study seems like they’re deliberately hiding things from us or trying to remain obscure.
Methods:
This is an observational study, meaning they didn’t have any controls. 80% of patients got a CT chest and (almost) every patient had a daily nasopharyngeal swab.
They all got an EKG before treatment and two days after treatment began. They had criteria to not start therapy based on some findings listed in the article.
Treatment regimen:
Hydroxychloroquine 200mg three time a day for 10 days
Azithromycin 500mg on day 1, then 250 daily for 4 days
End points (these are not your typical endpoints): Clinical Outcome (oxygen therapy or ICU transfer)
Contagiousness by PCR and culture
Length of stay in the ID ward
Things to know:
n=80
4 patients were asymptomatic carriers (then why were they in the COVID unit?)
92% of the patients were less ill based on their made up NEWS score
52.8% had lower respiratory infections/pneumonia.
Results:
We don’t have any controls to know if this is the normal course of the infection or if the hydroxychloroquine actually worked or not. I forgive them for not having controls in the prior study but this is now too much.
93.8% were discharged with a low NEWS score. Don’t forget that 92% had a low news score to begin with!
3 patients still ended up in the ICU.
The nasopharyngeal viral load fell. Sure. Cool. Thanks. But does this normally fall at this rate without treatment? We need controls. Is the decrease in contagiousness the normal evolution or the drugs working? We don’t know. No controls.
I’m tired of reviewing this study. You all get my point. I am in favor of trying it, but I feel like there’s some academic dishonesty happening here.
I really want this to work, really really do. We need some good news but we also need to solidify our management with better data.
-EJ
Hydroxychloroquine & Azithromycin in COVID-19: Updated on 3/29/20
First of all, credit to the authors. Huge hat tip to them.
Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949
First of all, there are a substantial amount of limitations to the study but in my opinion, not medical advice, it provides a glimmer of hope.
Let’s begin Where was it performed: French study (thank youuuuuu!) Population: NOT ICU Patients! But we’ve learned that non-ICU patients become ICU patients extremely quick! n=36 (20 hydroxychloroquine, 16 control) How did the determine the Viral load? Nasopharyngeal swabs daily
Questions I have: 6 patients (originally n=42) lost to follow up. Patients who were transferred to the ICU were considered to be “lost to follow-up” (n=3). I can’t tell if the one patient who died was transferred to the ICU. Hopefully the edits will sort this out. Why didn’t they just follow those patients who ended up in the ICU?
Age groups were not matched but this would favor the control group as the experimental group was older. More were male in the experimental group which we assume that males get this worse than females. More asymptomatic patients in the control group, also bodes worse for the experimental arm. 3 classifications: asymptomatic, upper respiratory, lower respiratory
Regimen: Hydroxychloroquine 600mg daily (200mg TID x 10 days) +/- azithromycin depending on clinical presentation (500mg on day 1, 250mg x 4 days)
Results:
At day 6, 70% of hydroxychloroquine group were virologically cured vs. 12.5% in control group (p=0.001) NNT = 1.7!! 100% of hydroxychloroquine + azithromycin were virologically cured vs 57.1% in the hydroxychloroquine only group vs. 12.5% in the control group (p0.001) Drug effect was higher in URI and LRI than asymptomatic patients (p=0.05) Starts working in 3-6 days per this data. Careful with the QT prolongation on the EKG! Replete the Mg as needed for this. Monitor liver function. My pharmacy friends can contribute some more adverse effect stuff like retinopathy, etc. I cannot make any recommendations as I do not give medical advice but I know what I would do with this data to save a life. -EJ LINK TO FULL FREE PDF!!
An Update on 3/29/2020
We have an update now from the same researchers in France. It’s a free PDF and I recommend you read it yourself. Don’t trust me.
Interesting that the authors mention potentially using ARBs, metformin, and statins as many have directly messaged me asking what I thought on these particular families of treatments. This study has me scratching my head. Their first study seemed like they rushed it out the door to start some more broad research. This study seems like they’re deliberately hiding things from us or trying to remain obscure.
Methods:This is an observational study, meaning they didn’t have any controls. 80% of patients appear to have gotten a CT of the chest and (almost) every patient had a daily nasopharyngeal swab.
They all got an EKG before treatment and two days after treatment began. They had criteria to not start therapy based on some findings listed in the article.
Treatment regimen:Hydroxychloroquine 200mg three time a day for 10 days
Azithromycin 500mg on day 1, then 250 daily for 4 days
End points (these are not your typical endpoints): Clinical Outcome (oxygen therapy or ICU transfer)
Contagiousness by PCR and culture
Length of stay in the ID ward
Things to know:n=80
4 patients were asymptomatic carriers (then why were they in the COVID unit?)
92% of the patients were less ill based on their made up NEWS score
52.8% had lower respiratory infections/pneumonia.
Results:
We don’t have any controls to know if this is the normal course of the infection or if the hydroxychloroquine actually worked or not. I forgive them for not having controls in the prior study but this is now too much.
93.8% were discharged from a low NEWS score. Don’t forget that 92% had a low news score to begin with!
3 patients still ended up in the ICU.
The nasopharyngeal viral load fell. Sure. Cool. Thanks. But does this normally fall at this rate without treatment? We need controls. Is the decrease in contagiousness the normal evolution or the drugs working? We don’t know. No controls.
I’m tired of reviewing this study. You all get my point. I am in favor of trying it, but I feel like there’s some academic dishonesty happening here.
I really want this to work, really really do. We need some good news but we also need to solidify our management with better data.
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