Ivermectin Benefits Disappeared as Trial Quality Increased
A followup to an article I had read and previous findings.
Not the first time, a drug or drug combination has been disapproved. This usually comes from a lack of supporting evidence coming from clinical trials. Instead there are various studies conducted which show varying degrees of results which may have questionable data.
In the beginning of the COVID pandemic, everyone was hyping Hydroxychloroquine (HCQ) as the cure for COVID. As it turned out, the powers in charge of a approving drugs for the treatment of COVID did not agree with the others who were touting HCQ even when used as an ionophore for other drugs such as AZT (Azithromycin) or elements such as Zinc.
A copy of a portion of Figure 1 showing how Zinc would block the CCOVID virus from attaching to cellular ACE2.
Preventing Viral Replication
Frontiers | The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis | Immunology (frontiersin.org)
The theory or reasoning behind using Zinc in conjunction with HCQ is it prevents the replication of COVID. More Zinc can enter the cell by using HCQ as an ionophore.
Didier Rauolt touted the combination of HCQ and AZT. His studies were incomplete. Henry Ford Hospitals did do a study using ~ 2500 patients over a period of time.
No clinical trials have been completed testing whether Zinc would be effective in the treatment of COVID.
It was suggested that zinc can prevent fusion with the host membrane, decreases the viral polymerase function, impairs protein translation and processing, blocks viral particle release, and destabilizes the viral envelope (35, 37, 40). Low-dose zinc supplementation together with small concentrations of the zinc ionophores pyrithione or hinokitol decreased RNA synthesis in influenza, poliovirus, picornavirus, the equine arteritis virus, and SARS-CoV by directly inhibiting the RNA-dependent RNA polymerase of the virus (34, 41). There is evidence that zinc can enhance the effect of chloroquine, another known zinc ionophore, while zinc ionophores like epigallocatechin-gallate or quercetin remain to be tested. Frontiers | The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis | Immunology (frontiersin.org)
HCQ testing, Henry Ford Hospitals Study, Michigan
Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19 – International Journal of Infectious Diseases (ijidonline.com)
Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4–10 days), median age was 64 years (IQR:53–76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3–53). Overall in-hospital mortality was 18.1% (95% CI:16.6%–19.7%); by treatment: hydroxychloroquine + azithromycin, 157/783 (20.1% [95% CI: 17.3%–23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%–15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%–30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%–31.0%]). Primary cause of mortality was respiratory failure (88%); no patient had docume nted torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 [95% CI:1.9–3.3]), white race (HR:1.7 [95% CI:1.4–2.1]), CKD (HR:1.7 [95%CI:1.4–2.1]), reduced O2 saturation level on admission (HR:1.5 [95%CI:1.1–2.1]), and ventilator use during admission (HR: 2.2 [95%CI:1.4–3.3]). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine + azithromycin 71% compared to neither treatment (p < 0.001).
In the end Henry Ford Hospitals was calling for trials beyond their studies. Nothing more came of this.
More recently, there has been a push for the use of an animal deworming med. It was reported on other blogging
Ivermectin Benefits Disappeared as Trial Quality Increased
MedPage Today has an article on using Ivermectin to treat COVID and the studies supporting the use of it. Upon additional examination of the studies, it was found the study results suppo rting Ivermectinappear to be flawed.
In Re-Analysis, Ivermectin Benefits Disappeared as Trial Quality Increased | MedPage Today, “When studies with a moderate or greater risk of bias were removed, the survival benefit vanished for Ivermectin.”
Some detail from MedPage Today on their findings as to whether the findings from the various studies support the conclusion of Ivermectin were true or not-so-true. The latter appears to be reality. and those supporting the former should know better.
I find it disturbing that some tout the use of a drug which has not been trialed and has less of a chance of working than what I described about with the combination of HCQ and Zinc or AZT.
Dr. Andrew Hill PhD, Department of Pharmacology and Therapeutics, University of Liverpool:
“I’ve been working in this field for 30 years and I have not seen anything like this. I’ve never seen people make data up. People dying before the study even started. Databases duplicated and cut and pasted.”
The retracted study by Elgazzar et al. was reported to have included data that showed a third of the people who died from COVID-19 were already dead when trial recruitment began, and some appeared to have been hospitalized before they started — raising questions about the study’s prospective randomized nature.
In Re-Analysis, Ivermectin Benefits Disappeared as Trial Quality Increased | MedPage Today
For the re-analysis, Andrew Hill, PhD, of the University of Liverpool in England, and colleagues included 12 studies with 2,628 participants, and assessed them for bias. Overall, four studies had a low risk for bias, four studies had moderate risk, three studies were at high risk for bias, and one was potentially fraudulent.
- Taken at face value, the overall meta-analysis found a 51% increase in survival with ivermectin (P=0.01), but excluding the potentially fraudulent trial, Ivermectin’s benefit fell to 38% and was of borderline significance (P=0.05), they reported.
- Taking out the studies with a high risk of bias led to a further drop — down to a nonsignificant 10% increase in survival (P=0.66), they noted. Further removing studies with a moderate risk of bias took the benefit down to 4% (P=0.9).
Hill: “This has made me more wary about trusting results when you don’t have access to the raw data, We took them on trust and that was a mistake.”
The retracted study by Elgazzar et al. was reported to have included data that showed
- a third of the people who died from COVID-19 were already dead when trial recruitment began, and
- some appeared to have been hospitalized before they started — raising questions about the study’s prospective randomized nature.
Hill: “During the process of re-analysis, he also found a trial from Lebanon in which the same 11 patients had been “cut and pasted” repeatedly in the database.
It was quite shocking, really,”
The latter information was taken from: In Re-Analysis, Ivermectin Benefits Disappeared as Trial Quality Increased | MedPage Today
Me: Look, I am a manufacturing person who knows Supply Chain and the flows of materials and product through manufacturing stations. I worked in healthcare supplies and with the manufacture of pharmaceuticals.
Some people really do know economic policy and some abuse others with their knowledge.
Some internet pundits tout unproven cures which can be harmful and down – right dangerous. There is less of a basis for Ivermectin than there was for HCQ and Zinc or AZT. Some government officials have been doing the same. Indeed, both sources should know better.
HCQ in combination appeared to have a degree of impact early on in the treatment of COVID. Unfortunately and as the Ford researchers noted “politics” raised its ugly head again.
As a programmer/analyst from the dinosaur era, I am very familiar with the cut-and-paste method of test data creation. Most often the data was rigged to make any errors more obvious or test the limits applied by the algorithms. If such a data set was mistaken for the actual trial data, the competence of everyone with any part in the study needs a review. Every place I ever worked had rules and procedures to prevent test data and live data from any contact, much less comingling. I have to wonder if it was not malice on the part of someone in the study.
Hi . . .
That is just one study out of a bunch which made it. There are obvious issues here.
Drug development is full of great ideas only a few of which actually lead to new, effective treatments. Zinc sounds like a great idea for COVID and other respiratory ailments, but has yet to be validated as treatment.
The body already has a zinc metabolism. It tries to maintain a certain level of available zinc. If you want to increase that zinc level, you have an ADME problem. You have to get the body to Absorb enough of it, Distribute it to the right places, be available in the right form for Metabolism and deal with the body’s zinc Elimination system. Suppose the mechanism outlined in this post is correct, how does one get enough zinc in place to make it work as a treatment? If someone has a zinc deficiency, there are zinc supplements, but otherwise it might require zinc infusions to get the level required. How much zinc are we talking about, and what active form would be useful? (Let’s ignore the other issues of how quickly the body gets rid of excess zinc and whether high concentrations of zinc might cause other problems.)
P.S. Anything with SIRT in it has a red flag. Glaxo, among others, has pissed a lot of money down the tube trying to develop drugs using related metabolism. I’m not saying it won’t be part of some wonder drug in the future, just that people in the field have gotten skeptical.
Retraction Watch reports the retraction of the study with the cut and pasted data. The explanation was that they incorrectly submitted a training spreadsheet instead of the actual data. They may resubmit with the correct file.
Bunch of amateurs
Some more info, Ivermectin Study Retracted After Data Found To Be Completely Wrong
We had a conversation about this over a year ago. A New Covid Study – Angry Bear (angrybearblog.com)
Really, this is not a promotion of HCQ. HCQ Plus AZT or Zinc was the point and it had better studies than the touted Ivermectin did, and was rejected. Here again, the combination had to be used in the early stages of COVID.
It was never trialed beyond the Henry Ford studies and Fauci wrote it off as just HCQ.
There are people promoting Ivermectin as a cure. It is suspect at best. The HCQ plus Zince or AZT had better data.
The HCQ is used as an Ionophore for the Zinc which attaches to the ACE2 and inhibits Covid fron attaching.