Was just about to post this!

So my reading of this is it was a retrospective open label study. The distribution of conditions, age, sex, symptoms were mostly comparable between the groups. Despite it not being a prospective RCT and having low n, the P-values are very good for the Duration of viral clearance, hospital stay, and mortality numbers. How can we argue a psychosomatic effect yielding the results in the treatment group when the results are so significantly different?

Also worth noting that none in the treatment group developed pneumonia or ischemic stroke, suggesting that IVM had some impact on hypercoagulability. In the non-IVM group 13 (9.8%) developed pneumonia and 2 (1.5%) developed stroke. This is reflected by more people the non-IVM group needing oxygen - that the IVM group receiving oxygen were not classified has developing pneumonia is questionable.

Some comments: The study does not specify what antibiotic was used (so we don't know whether Doxycycline was used in all cases). The lower median age could be attributed to the better survival rates, but the comparison of the two results is strong. The IVM treatment cohort also had a much higher proportion of males, who statistically are more likely to die.

Overall really good results.

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Median age 35 is what makes it not that strong. Still good evidence on the good side.

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https://www.sciencedirect.com/science/article/pii/S030028962030288X Ivermectin Treatment May Improve the Prognosis of Patients With COVID-19

Summary:

This retrospective study of ivermectin use from Bangladesh which has authors from Bangladesh and Japan collected data on patients who had been previously treated into two arms:

• 115 received ivermectin plus standard care

• 133 received only standard care

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Disease progression was better across the board for all metrics - ivermectin vs non-ivermectin:

• Developed moderate respiratory distress - 3 (2.6%) vs 21 (15.8%) - p<0.001

• Developed pneumonia - 0 (0%) vs 13 (9.8%)

• Ischemic stroke - 0 (0%) vs 2 (1.5%)

• Required intensive care management - 1 (0.9%) vs 11 (8.3%) - p<0.001

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Clinical outcomes were better across the board for all metrics - ivermectin vs non-ivermectin:

• Duration of viral clearance, median (IQR) – day - 4 (4–6) vs 15 (12–17) - difference: 9.78 (8.97–10.59) - p <0.001

• Duration of hospital stay, median (IQR) - day - 9 (7–10) vs 15 (12–19) - difference: 6.3 (5.09–7.51) - p<0.001

• Recovered and discharged - 114 (99.1) vs 124 (92.2) - difference: 0.516

• Death - 1 (0.9%) vs 9 (6.8%)

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In addition for the ivermectin group:

• there were more males - who do worse usually than females

• used less antibiotics

• used less supplemental oxygen (ie ivermectin group did better)

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Thus ivermectin seems to:

• reduce progression of disease

• reduce mortality

• increases the rate of viral clearance (early)

• decreases hospital stays

• no adverse effects in ivermectin group (note though that they did use a low dose of 12mg one time ivermectin within 24 hours of admission - other studies have reported mild gastric symptoms in a few patients)

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Questions

As video below points out, paper is not clear which groups received steroids (treatments mentioned are antipyretics, antihistamines etc. but not steroids) - since steroids also improve mortality - however, since the patients were mostly young (below 50 years of age) in this study, it is possible steroids were mostly not used (but should have been for serious cases - perhaps this study was conducted after WHO directed against use of steroids - which they later reversed).

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Here is a video analysis of this paper/letter by Whiteboard Doctor:

https://www.youtube.com/watch?v=_UvZHJh_wdk

Ivermectin And COVID-19: New Study On Viral Clearance, Hospital Length Of Stay, And Mortality.

Here we will discuss a new study that was published out of Bangladesh in a Spanish Respiratory Medicine Journal called Archivos De Bronconumologia looking at Ivermectin for the treatment of COVID-19 in hospitalized patients. We will discuss what Ivermectin is, how it is theorized to work, and why it is being studied. We will then dive into the study including the doses of Ivermectin used, the study structure, the study population, and their findings. They found decreased development of moderate respiratory disease, decreased escalation to the intensive care unit, faster viral clearance (even compared to three other anti-virals), decreased length of stay in the hospital, and decreased mortality. Pretty impressive! What do these results mean? What are the limitations? Where to go from here? Check out the video for all the details and more!

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Put this one in the win column for ivermectin. What is the score now, 8 for 9?

AFAIK, this trial wasn't registered. Edit: It's not in ClinicalTrials, anyway. I asked the primary author if it is registered. Hope he answers!

Highlights:

• COVID-19 patients receiving ivermectin became SARS-CoV-2 negative more quickly

• Fewer ivermectin-treated patients developed respiratory distress

• Ivermectin-treated COVID-19 patients had shorter hospital stays

• Ivermectin is associated with a lower mortality rate in COVID-19
  patients

325 PCR-confirm covid+ patients. 248 were free from other serious health problems. The 248 were divided into 115 who received ivermectin plus standard care; the remaining 133 received only standard care. There's no more information about how the patients were assigned to the two groups. It wasn't by random assignment (they would have said so, and then this would be a prospective study, I think).

The ivermectin group received one dose of 12mg on Day 1 of hospitalization.

All 248 subjects received standard care: antipyretics for fever, anti-histamines for cough, and antibiotics to control secondary infection.

(Which antibiotics?) Later: The author replied (see below) and said Azithromycin as the antibiotic used. I'm surprised it's not doxycycline.

The treatment did not produce any aberrant symptoms related to ivermectin use.

None of the ivermectin-treated patients showed progressive pathology, such as pneumonia or cardiovascular complications.

Significantly fewer ivermectin-treated patients:

• developed pneumonia (0% vs 9.8%)

• had ischemic strokes (0% vs 1.5%)

• required oxygen inhalation (9.6% vs. 45.9)

• developed respiratory distress (2.6% vs. 15.8%)

• needed antibiotic treatment (15.7% vs. 60.2%)

• needed intensive care management (0.9% vs. 8.3%).

Interestingly, the patients receiving ivermectin

• became SARS-CoV-2 negative more quickly (median 4 vs. 15 days; 95% CI, 8.97–10.59; P<0.001).

• had shorter hospital stays (median 9 vs. 15 days; 95% CI, 5.09–7.51; P<0.001).

• had significantly lower fatalities (0.9% vs. 6.8%; P<0.05).

Of the ivermectin-treated patients, 61 were randomly assigned for follow-up assessment 10 and 20 days after discharge; none of them were reported any complications.

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TrialSiteNews's story about this trial.

Edit: Someone on twitter took this from the TSN article:

No IVM patients developed pneumonia vs 10% of standard care. Fewer than 10% IVM patients needed oxygen versus 50% standard care. IVM patients negative in 4 days versus 15 days standard care.

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Something I hadn't noticed: a couple of the authors have Bangladeshi-sounding names but they're located at medical schools in Japan!

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Here is someone's comments on the article on twitter. it's only mostly accurate (typed with Miracle Max's voice).

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In the Department of Vaguely Amusing Department:

I posted this study to /r/covid19 3 hours ago. Googling for new ivermectin articles just now, this. Weirdly, the text that appears right after the title is not in the post.

Is Google losing it?

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My write-up from /r/COVID19:

This is a retrospective trial that was done in Bangladesh, accepted by the Archivos de Bronconeumología. I asume that makes it peer-reviewed.

From a population of 325 PCR-confirmed covid+ patients, 248 were found to be free from other serious health problems. The 248 were divided into a group of 115 who received ivermectin plus standard care; the remaining 133 received only standard care. Wow: an (almost) proper control arm!

There's no information about how the patients were assigned to the two groups. It wasn't by random assignment; they would have said so (and then this would be a prospective study, I think). I suspect that individual doctors made the decision to use ivermectin or not. That's how it worked in the Broward County ICON study. It was that study's principle flaw.

Uniquely, the primary author of the study joined reddit 11 hours ago so he could post thanks for the study's write-up in /r/ivermectin. (How cool is that!) I replied to his post, asking how subjects were allocated to the with- and without-ivermectin groups. I hope he answers!

It's not a perfect design. What else is new?

You RCT snobs (whom I respect, RCTs are the best evidence) can stop reading now. Please don't bother to post that we can't learn anything from observational studies. That's gotten old and isn't true. Ivermectin isn't vitamin D (lame joke).

True fact: I asked a smart /r/ivermectin reader to post this study to /r/covid19. He refused, saying that he's intimidated by this sub. Criticize away, but be nice about it, please.

While it (apparently) didn't use random assignment, the study gets points for presenting comparisons of the two groups on many attributes. There are no statistically significant differences except gender: the ivermectin group is 69.6% male and the no-ivermectin group is 51.9% male (p < 0.01). That actually cuts in favor of the study results being valid, since males do comparatively poorly with covid-19. The with-ivermectin group was disadvantaged by being more male.

Some more statistically insignificant differences between the two groups, and some very stat-sig results are here.

Question: It is weird that many of the comparisons use median instead of mean?

All 248 subjects received standard care: antipyretics for fever, anti-histamines for cough, and antibiotics to control secondary infection. Per the author's post on /r/ivermectin: the antibiotic used was azithromycin. This is a break with the other Bangladesh trials: they all used doxycycline. Maybe azithromycin works better!

The ivermectin group received one dose of 12mg on Day 1 of hospitalization.

Skip the next paragraph, if you're not interested in ivermectin dosing. [Everyone skips.]

12mg is the minimal dose. Most (I venture) trials use more ivermectin, either larger single doses or doses over multiple days. The FDA recommends 200mcg/kg of ivermectin for the treatment of strongyloidiasis (roundworm). It shows the FDA's worldwide influence, that 200mcg/kg is the low-end default dose in a number of ivermectin trials. This trial applies the FDA's guidance poorly: 12mg is less than 200mcg/kg if the patient weighs more than 60kg / 132 pounds. In many trials and in treatment of covid-19 patients, 18mg is often used for patients over 90kg / 198 pounds; and the dose goes up to 24mg for 105kg / 231 pound patients. At those weight breaks and milligrams, the dose is 200mcg/kg. As you have probably guessed, in many locales, ivermectin comes in 6mg tablets. The highest-dose trial is giving subjects 1200mcg/kg for 5 consecutive days! Right after the ivermectin is given on the 5th day, the blood level of ivermectin (computed from the drug's half-life) is only 6mcg/kg less than the 2000mcg/kg maximum found to be safe, in the safety study that looked at the highest doses. The most aggressive treatment protocol doses 105+ kg patients at 857mcg/kg (that's 30 mg) given three times a day. That's for patients in critical condition.

Seeing a single dose of 12mg, without even allowance for weight, is discouraging.

However, the results are remarkable! They're consistent with what we've seen in the other ivermectin trials, but even more so. For example, in other trials, ivermectin appears to shorten length of stay in the hospital. This trial shows the same thing, by a larger number of days than seen in the other trials.

Results:

Compared to 133 controls, the 115 patients given ivermectin:

• had fewer fatalities (0.9% vs 6.8%; P<0.05)

• became covid-negative faster (median 4 vs 15 days; 95%; P<0.001)

• had shorter hospital stays (median 9 vs 15 days; P<0.001)

Fewer ivermectin-treated patients:

• needed the ICU (0.9% vs 8.3%)

• needed oxygen (9.6% vs 45.9%)

• needed antibiotics (15.7% vs 60.2%)

• had respiratory distress (2.6% vs 15.8%)

• developed pneumonia (0% vs 9.8%)

• had ischemic strokes (0% vs 1.5%)

Also:

• The treatment did not produce any aberrant symptoms related to ivermectin use.

• None of the ivermectin-treated patients showed progressive pathology, such as pneumonia or cardiovascular complications.

• Of the ivermectin-treated patients, 61 were randomly assigned for follow-up assessment 10 and 20 days after discharge; none of them reported any complications.

Pretty good study! Needless to say, further research is needed.

There are at least 60 not-yet-incompleted ivermectin trials. It's impossible to guess how many will actually get completed. At present, 39 of the trials are registered at ClinicalTrials.gov. Of those, 11 have not started recruiting and 18 are in the process of recruiting. Only 4 are "Active", which I take as meaning "This trial is underway right now: patients are getting ivermectin, etc."

I take it as a good sign, that a lot of trials were added in July and August, as you can barely see from this site's graph of ivermectin trial registration dates here (the tiny blue lines). 3 trials were added in September, including a true RCT out of Bangladesh!

AFAIK, this trial was not registered. I asked the author about that too. How many more unregistered ivermectin trials are lurking out there? At least a few.

In the spirit of Game of Thrones, leaving aside season 8:

Data is coming

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Whiteboard Doctor's discussion of this study.

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