TL;DR: We don't have enough good research about ivermectin vs covid19 yet. (Duh!)
A recent study reported that ivermectin was successfully used in vitro for the treatment of SARS-CoV-2 in experimentally infected cells, and two preprint publications reported observational clinical studies on the apparent utility of ivermectin to treat patients with COVID-19 needing mechanical ventilation. However, none of these studies was peer-reviewed nor formally published and one study was later retracted.
The in vitro study was Monash 48 hours. The two preprint studies (I am guessing) are the Broward County report and the Surgisphere study.
The Surgisphere ivermectin study was not formally retracted; it was removed from SSRN because one of the authors (Mehar) thought that more work needed to be done on it, or something to that effect -- in the aftermath of the Surgisphere "scandal" that led to a Lancet and a BMJ article being retracted. IMO the only thing wrong with the 3 studies is the data came from a black box that the owner refused to allow to be audited, after saying he would. There's no reason to think the ivermectin study is invalid.
A link to the Surgisphere ivermectin study is available here.
The Pan American Health Organization (PAHO) compiled an evidence database of potential COVID-19 therapeutics for which a rapid review was conducted of all COVID-19 in vitro (lab) and in vivo (clinical) human studies published from January to May 2020. The review concluded that the studies on ivermectin were found to have a high risk of bias, very low certainty of the evidence, and that the existing evidence is insufficient to draw a conclusion on benefits and harms.
I can't disagree. The Broward County "study" is poor-quality research. The Bangladesh study didn't have a control arm. Sigh.
Though the effectiveness of ivermectin is currently being evaluated in various randomized clinical trials, the World Health Organization (WHO) excluded ivermectin from its co-sponsored Solidarity Trial for COVID-19 treatments, a global effort to find an effective treatment for COVID-19.
This isn't fair, really; ivermectin wasn't on the map when Solidarity got underway.
The Mectizan® (ivermectin) Expert Committee Statement on Potential Efficacy of Ivermectin on COVID-19 emphasized that the laboratory results showing efficacy of ivermectin to reduce viral loads in laboratory cultures, at dosage levels far beyond those approved by the FDA for treatment of parasitic diseases in humans, are not sufficient to indicate that ivermectin will be of clinical benefit to reduce viral loads in COVID-19 patients.
This is a specious argument, IMO. There is no known maximum dose limit for ivermectin. One good study examined that and concluded that 10 times the FDA approved 200mcg/kg was safe. The Israel trial will be dosing at 1200mg/kg for 5 consecutive days. I think that dose will approach the levels deemed too much by the two researchers who wrote letters that were published with the Monash 48 hours study -- which have been echoed by maybe 10 articles, including this one.
Chaccour et al. caution against using in vitro findings as more than a qualitative indicator of potential efficacy and emphasize that “due diligence and regulatory review are needed before testing ivermectin in COVID-19...
I know little about LD50 calculations. I guess it means that 200mg/kg would kill half the patients. Any idea how that was calculated? I've never come across any source for that.
Is an LD50 usually associated with a normal curve with a known standard deviation -- which would allow predictions of the overdose fatality rates for doses at (for example) 3 standard deviations below the LD50?
Yes that is exactly what LD50 means. The LD50 is derived from other animals. The LD50 for humans is not exact. In various articles I see it listed as 250mg/kg, as a range 50mg/kg - 300mg/kg, or as a min 15mg/kg.
Several studies say the LD50 is 250X the therapeutic dose. This would place it at 50mg/kg. This is probably a good enough number. I'll edit my previous comment to reflect this.
I know it has been safely tested up to at least 2000mcg/kg (2mg/kg) in humans.
[-] TrumpLyftAlles | 2 points | Jul 01 2020 22:54:44
TL;DR: We don't have enough good research about ivermectin vs covid19 yet. (Duh!)
A recent study reported that ivermectin was successfully used in vitro for the treatment of SARS-CoV-2 in experimentally infected cells, and two preprint publications reported observational clinical studies on the apparent utility of ivermectin to treat patients with COVID-19 needing mechanical ventilation. However, none of these studies was peer-reviewed nor formally published and one study was later retracted.
The in vitro study was Monash 48 hours. The two preprint studies (I am guessing) are the Broward County report and the Surgisphere study.
The Surgisphere ivermectin study was not formally retracted; it was removed from SSRN because one of the authors (Mehar) thought that more work needed to be done on it, or something to that effect -- in the aftermath of the Surgisphere "scandal" that led to a Lancet and a BMJ article being retracted. IMO the only thing wrong with the 3 studies is the data came from a black box that the owner refused to allow to be audited, after saying he would. There's no reason to think the ivermectin study is invalid.
A link to the Surgisphere ivermectin study is available here.
The Pan American Health Organization (PAHO) compiled an evidence database of potential COVID-19 therapeutics for which a rapid review was conducted of all COVID-19 in vitro (lab) and in vivo (clinical) human studies published from January to May 2020. The review concluded that the studies on ivermectin were found to have a high risk of bias, very low certainty of the evidence, and that the existing evidence is insufficient to draw a conclusion on benefits and harms.
I can't disagree. The Broward County "study" is poor-quality research. The Bangladesh study didn't have a control arm. Sigh.
Though the effectiveness of ivermectin is currently being evaluated in various randomized clinical trials, the World Health Organization (WHO) excluded ivermectin from its co-sponsored Solidarity Trial for COVID-19 treatments, a global effort to find an effective treatment for COVID-19.
This isn't fair, really; ivermectin wasn't on the map when Solidarity got underway.
The Mectizan® (ivermectin) Expert Committee Statement on Potential Efficacy of Ivermectin on COVID-19 emphasized that the laboratory results showing efficacy of ivermectin to reduce viral loads in laboratory cultures, at dosage levels far beyond those approved by the FDA for treatment of parasitic diseases in humans, are not sufficient to indicate that ivermectin will be of clinical benefit to reduce viral loads in COVID-19 patients.
This is a specious argument, IMO. There is no known maximum dose limit for ivermectin. One good study examined that and concluded that 10 times the FDA approved 200mcg/kg was safe. The Israel trial will be dosing at 1200mg/kg for 5 consecutive days. I think that dose will approach the levels deemed too much by the two researchers who wrote letters that were published with the Monash 48 hours study -- which have been echoed by maybe 10 articles, including this one.
Chaccour et al. caution against using in vitro findings as more than a qualitative indicator of potential efficacy and emphasize that “due diligence and regulatory review are needed before testing ivermectin in COVID-19...
This is obvious to everyone. Trials are coming!
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[-] DZinni | 2 points | Jul 02 2020 01:10:27
Small correction, it's 200mcg/kg (0.2mg/kg). The LD50 is estimated to be around 50mg/kg.
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[-] TrumpLyftAlles | 1 points | Jul 02 2020 01:17:15
Good catch, corrected, thank-you!
I know little about LD50 calculations. I guess it means that 200mg/kg would kill half the patients. Any idea how that was calculated? I've never come across any source for that.
Is an LD50 usually associated with a normal curve with a known standard deviation -- which would allow predictions of the overdose fatality rates for doses at (for example) 3 standard deviations below the LD50?
permalink
[-] DZinni | 2 points | Jul 02 2020 03:30:28
Yes that is exactly what LD50 means. The LD50 is derived from other animals. The LD50 for humans is not exact. In various articles I see it listed as 250mg/kg, as a range 50mg/kg - 300mg/kg, or as a min 15mg/kg.
Several studies say the LD50 is 250X the therapeutic dose. This would place it at 50mg/kg. This is probably a good enough number. I'll edit my previous comment to reflect this.
I know it has been safely tested up to at least 2000mcg/kg (2mg/kg) in humans.
permalink