Read and make your own decision, but the data speak to me:
Viral clearance was treatment dose- and duration- dependent. In 11 randomized trials of moderate/severe infection, there was a 56% reduction in mortality (Relative Risk 0.44 [95%CI 0.25-0.77]; p=0.004; 35/1064 (3%) deaths on
ivermectin; 93/1063 (9%) deaths in controls) with favorable clinical recovery and reduced hospitalization.
Update August 2023: In retrospect, evidence supporting the use of ivermectin for COVID-19 has been found to be due to either flawed or faked studies.
healthunlocked.com/cllsuppo...
Two 2022 @CureusInc papers were hailed by some as the most overwhelming positive results from observational studies of ivermectin for Covid-19.
We show that the results from both studies can be entirely explained by untreated statistical artefacts
twitter.com/gtuckerkellogg/...
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Medpage Today's report on this report: medpagetoday.com/special-re...
The authors concluded that their results "need to be validated in larger confirmatory trials" -- a fact that David Boulware, MD, MPH, of the University of Minnesota, who has been interested in evaluating ivermectin for COVID-19 outpatients, agreed with.
:
Boulware noted that there are multiple ongoing phase III randomized controlled trials "which will provide definitive results," including the U.K.'s PRINCIPLE outpatient trial that's aiming to enroll about 1,500 patients in its ivermectin arm.
I hope the PRINCIPLE trial or another phase III randomised controlled trial does indeed provide definitive results.
Neil
There has been a lot of interest in Ivermectin for over a year now. I can't help but feel that if big pharma could make money out of it, a decent phase lll trial would have been done months ago.
Thank you Neil. The article you shared was much easier for me to understand. Apart from the need for confirmatory trials, the takeaway points for me were:
▪️ Widespread vaccines “negate the need to use ivermectin as a treatment”
▪️ Use of ivermectin was associated with a reduction in time to recovery
▪️ Ivermectin was not associated with a lower risk of hospitalization
▪️ Studies also included a range of comparators, including hydroxychloroquine, lopinavir/ritonavir, standard of care, and placebo
▪️ Note: there was no mention of monoclonal antibodies in the range of comparators
Neil -
Do you have a link to the PRINCIPLE trial on clinicaltrials.gov?
Seymour, per principletrial.org/
PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research.
EudraCT number: 2020-001209-22 • ISRCTN registry: ISRCTN86534580 • REC number: 20/SC/058 • IRAS number: 281958
Currently investigating:-
- Favipiravir (an antiviral drug)
- Ivermectin (used to treat several types of parasitic infections)
- The usual standard of NHS care
Apparently no clinicaltrials.gov registration.
Neil
Thanks Brian. Is there any reason to suppose Ivermectin would be any less effective a treatment for Covid19 in CLL patients?
I was wondering about the same thing.
CLL patients have less robust immunologic response to COVID-19 infections, that can degrade our benefit from any and all therapies.
Bummer
Impressive!
Doc,
Would you take it?
Jeff
You bet. Almost no downside, big potential upside. But folks need to make their own decisions with the healthcare team.
Highly recommend on youtube the UCTV presentations from the University of California, and especially their COVID mini-medical school for the public on COVID. The final presentation is by Dr. Monica Gandhi, UCSF epidemiology expert who says, sadly, the data is in and that Ivermectin is not what had been hoped. UCSF has an impressive array of researchers and clinicians who report of their experience in the various front lines of research and patient care during these frightening COVID times. youtube.com/watch?v=GUQu5nU...
Lots of different opinions on ivermectin, most including mine well intentioned but poorly informed as the data are limited. I read it differently.
I'll go with UCSF Dr. Monica Gandhi any day, an emotion seconded by my internist who has lots of AIDS patients has been following her for some years.
Can't argue with that Hopefully the active RCT will given us a definite answer soon.
And perhaps I've come down too strongly against Ivermectin. I have an old college friend, a very well educated woman in some areas, who is against COVID vaccination and believes Ivermectcin will keep her safe. She also follows the horrible Medrcola, so I'm coming in on this discussion in a bad mood. Add to that, the reasonable view of my internist seen yesterday who thinks because of the low global vaccine rate, we are headed for immunity by vaccination, immunity acquired by disease, or death acquired by disease. And that this disease will be with us until one of those gets us. We know we with CLL are not getting robust antibody responses, especially those of us with low ALC from various treatments. Memory T cells are a wild card. Even the UK who touts its great vaccine program has only given 36% a 2nd jab. I think the UK opening up is the return to their original plan to get herd immunity through disease. And that was before the Delta variant.
Thanks for weighing in on this strange controversy. a pointed question: Covid will be endemic, how therefore would you like to be treated if infected with Covid?My preference would be to have monoclonal antibody, ASAP, take low risk Ivermectin. Vitamin D , C etc. Breathing treatments and exercises at home. To hospital hospital if Oxygen saturation drops say below 80%.
I bring this up as some of us will face this problem and be confronted with practitioners who have not thought this through. We are likely to be a bit on our own.
In addition, am gearing up to take booster targeted to newer variants, if offered, available, in the meanwhile.
Warmest regards.
Looks like dose of Ivermectin could be anywhere from .2mg/kg to 2mg/kg of body weight, and from 1 to 4 days.
BTW had 3rd vaccine JNJ, after 2 doses of Moderna with no antibody response either time. My own experiment. Did have side effects both times--flu like 2 days or so. I am on Ibrutinib. I wonder if ANYONE on Ibrutinb has had a response to vaccines? The mechanism of action clearly is disturbing antibody production from B cells. So maybe side effects driven by other immune response--T cell/NK cell, etc.
NY8,
Sorry to hear that you didn’t get any response to your J&J but thanks for the info.
Jeff
Only sharing for info as this just popped up. I've not even read it yet and I'm off to bed. theguardian.com/science/202...
Interesting link, Nic. Well worth reading..
Thanks, Nic. I was about to post something about the Guardian article, too. Here 'tis:
A major study suggesting that Ivermectin treatment is effective against COVID-19 has been withdrawn due to “ethical concerns”.
The preprint study on the efficacy and safety of ivermectin, led by Dr Ahmed Elgazzar from Benha University in Egypt, was published on the Research Square website in November 2020.
'The study found that patients with Covid-19 treated in hospital who “received ivermectin early reported substantial recovery” and that there was “a substantial improvement and reduction in mortality rate in ivermectin treated groups” by 90%.'
The Guardian article says that the study has been "pulled from the Research Square website on Thursday “due to ethical concerns”.
The Guardian quotes concerns raised by a medical student, Jack Lawrence, who examined the study as a Master's assignment and found that 'the introduction section of the paper appeared to have been almost entirely plagiarised.' He also found discrepancies in the data and 'contacted an Australian chronic disease epidemiologist from the University of Wollongong, Gideon Meyerowitz-Katz, and a data analyst affiliated with Linnaeus University in Sweden who reviews scientific papers for errors, Nick Brown, for help analysing the data and study results more thoroughly.'
Brown created a comprehensive document uncovering numerous data errors, discrepancies and concerns ...'
The Guardian article provides links to the analysis by Lawrence and Brown.
Hi Brian,
After CLLerinOz alerted me about The Guardian article theguardian.com/science/202... and which BellaBee10 quoted in her reply, I read through the blog analysing the trial data from the pro Ivermectin study and downloaded and looked at the spreadsheets from Nick Brown's blog steamtraen.blogspot.com/202... . No wonder the study got retracted! Obtaining a meaningful analysis from that raw data is a farce - even before considering all the problems with the figures identified by Nick Brown. The date information in the raw data was never corrected (this is easy to do and I do it regularly when working with spreadsheets). As Nick Brown has extensively noted in his analysis, if you correct the data, you get lots of different statistical results from those mentioned in the paper, so the claims in the pulled study can't have come from an analysis of the raw data.
It's totally understandable how the meta-analysis paper you cited was influenced by this withdrawn paper, given per the The Guardian article:
“Because the Elgazzar study is so large, and so massively positive – showing a 90% reduction in mortality – it hugely skews the evidence in favour of ivermectin,” Meyerowitz-Katz said.
“If you remove this one study from the scientific literature, suddenly there are very few positive randomised control trials of ivermectin for Covid-19. Indeed, if you get rid of just this research, most meta-analyses that have found positive results would have their conclusions entirely reversed."
Per Nick Brown's Conclusion (with my emphasis, where I strongly agree)
"In view of the problems described in the preceding sections, most notably the repeated sequences of identical numbers corresponding to apparently "cloned" patients, it is difficult to avoid the conclusion that the Excel file provided by the authors does not faithfully represent the results of the study, and indeed has probably been extensively manipulated by hand.
:
I urge the authors to make their SPSS data file publicly available without delay, in order that we can see the exact numbers on which their analyses were based—because, as demonstrated above, those numbers cannot be those in the Excel file. If the authors cannot provide their SPSS data file then I believe that either they or Research Square should consider retracting their preprint as a matter of urgency."
I've done plenty of data capture and analysis in my career using Excel and initially considered that some data could have been inadvertently included a few times - it's not an unusual occurrence. However, the slight variations in the nearly duplicated records exclude that likelihood.
Jack Lawrence in his article "Why Was a Major Study on Ivermectin for COVID-19 Just Retracted?" grftr.news/why-was-a-major-... noted, "Every patient in the severe COVID-19 group receiving standard care was an ICU patient, while the patients with severe disease in the ivermectin group were mixed between wards and ICU."
SeymourB references a similarly sized study of patients (500) showing no benefit: bmcinfectdis.biomedcentral....
healthunlocked.com/cllsuppo...
Likewise this meta-analysis
academic.oup.com/cid/advanc...
Surprise, surprise!
"After excluding the data from the Elgazzar study, (Meyerowitz-Katz) found that the effect for ivermectin drops significantly with no discernible effect on severe disease. Meyerowitz-Katz later also reran the analysis while excluding an additional poor-quality study and found that after this ivermectin showed no effect in treating COVID-19."
I hope that the University of Oxford PRINCIPLE study resolves the Ivermectin debate for once and for all. It's bad enough when data we rely on to keep people safe has such serious errors and distracts efforts that could be used to better effect elsewhere to save lives, let alone apparently fabricated. Words fail me.
Neil
Very disturbing. One needs to read every detail of every trial it seems. I am glad some good RCT are coming.
Brian -
Unlike the vast majority of ivermectin studies, that BMC study was a double blind, placebo-controlled RCT, in a large patient population. It's hard to ask for more. Not only did ivermectin not prevent hospitalizations, those on the ivermectin arm ended up on ventilators sooner. That's not considered an adverse event, but would have been touted as a good sign if the reverse were true.
Even though there were 250 in each arm of that study, Table 2 shows that only 4 people died on ivermectin plus Standard of Care vs 3 on placebo plus Standard of Care. The deaths were considered all-cause mortality, not necessarily due to COVID-19. I would have preferred 10 or 100 times more people in each arm (2500 to 25000), like we see on things like vaccine studies to get better number for mortality as well as ventilators.
It's been a year now that ivermectin has been studied. I know it's hard to design and administer such studies, but there's been a noticeable flouting of science in the FLCCC group. Early on, they argued that there was no time. I think now, they are happy with their financial support, and afraid of walking back any statements. The FLCCC patients in the U.S. are not likely to file suit if someone dies.
Normally, I like meta-analysis and reviews. We always must be wary in such reviews of stats such as totals and averages calculated across studies that used different controls, patient populations, and methods - it's the 1st thing to look for in such reviews. Usually, some sort of consensus becomes apparent if good research standards are used. But I think COVID-19 has spawned a ton of poor research in the haste to get a piece of the publishing pie onto resumes.
The poor quality of much of the ivermectin research cited, combined with changes in standard of care would beg us to pay close attention to the Limitations section in the meta-analysis. I would have preferred a review focused on a narrower set of higher quality studies, since it is so easy to dismiss the entire meta-analysis by citing the faults of the worst studies it cites, such as the now notorious Elgazzar study, where the editor of a national journal fabricated data.
Nevertheless, I do see a place for ivermectin in desperately overwhelmed hospitals in many countries. As others have noted, COVID-19 will be with us for a long time, and vaccinations will take years to catch up in many areas. Ivermectin is very inexpensive, and not demonstrably harmful in the general population.
While ivermectin appears to show some benefit, it is by no means a cure or 100% preventative. In non-blood cancer patients, the vaccine - where available - clearly performs much better. On most of the larger studies cited in the meta-analysis, people still die on ivermectin, and people still had long hospital stays on ventilation. The numbers I see for ivermectin are similar to numbers seen for therapies like anti-virals, most of which have been abandoned in the well financed developed world. At least ivermectin is cheaper and more available.
Most of us are very fortunate to live where we do. I do feel bad asking for monoclonals as prophylaxis while others don't have beds or oxygen, much less access to steroids.
=seymour=
It seems like especially in the USA we are going to hit a ceiling in terms of the number of people vaccinated. Thus the goal of getting to herd immunity will become moot.
They need to put the amount of effort they put into vaccine development into treatment development or repurposing.
The vaccination campaign is not going to work since it has become too controversial.
A new approach needs the thrust that the vaccine development and investment had.
The discussions I watch on the news every night need to be completely changed.
We need to somehow get voices in the media to change the discussion. I think all walks of political life would agree that effective therapeutics would be noncontroversial.
We know prevention is the best medicine. But the reality of medicine is that most humans don't operate that way. We treat problems when they arise.
Message: please stay home 
Update.
