TrumpLyftAlles | 4 points
TLA writes about how it would be easy to do RCTs to establish ivermectin's efficacy with covid-19 patients and/or demonstrate prophylaxis.My first text post, maybe my last. Let me know if you think posts like this are inappropriate for the sub. I wrote the following way down in \r\covid19 where it will never been seen. Please contribute your critique or suggestions etc.
With IVM, we start with an axiom. IVM had RCTs = result safe (one of the safest drugs around). IVM had observational studies for covid19 = resut good. IVM has not had RCTs for covid19 yet. But it is not dangerous and will not be for covid.
IMO, this is an excellent argument in a nutshell for doing RCT trials with ivermectin. There is enough evidence to think it might work, and there's certainly enough evidence that's it's safe with covid-19, esp. no serious adverse events reported among 1500 (? haven't added it up) trial subjects.
Hospital X has its covid-19 standard of care. Why not randomly assign new covid patients to an ivermectin or no-ivermectin group and see what happens? There's no downside. All you need is a stream of covid-19 patients, a few hundred dollars worth of ivermectin and placebo, and time. Just check the medical records as you go, to make sure there's nothing untoward happening. Those records are the basis for the study report.
Testing prophylaxis with the general population is harder because getting infected is a low-probability event, even if you're in a hot spot. You would need a lot of subjects to step up, not a vaccine-trial sized number, but a lot. Maybe 10,000? Who will pay for that? NIH could, if they were interested. The fed is throwing money at a lot of other covid stuff.
You could always target vulnerable populations: nursing home residents, bus - subway - train commuters, health workers, who else?
Create 20 matched pairs of nursing homes, randomly assign one from each pair to the treatment or control groups, pass out appropriate pills to everyone, see what happens. Keep it blind by not telling the people who make follow-up phone calls what each nursing home received.
Ask people getting off the subway to participate, randomly assign half, give them big bottles of ivermectin or placebo, and follow up with phone calls or emails 6 months later to ask if they have tested positive. Or maybe just accept subjects with insurance, get their insurance information, and follow up via their medical records (with permission of course). That would capture fatalities, and give good information about length of stay, etc. with the survivors. The researchers could calculate the benefit-cost ratio, which if ivermectin really works, will be HUGE. It would make sense for the state government to pay for the study, or a consortium of state health insurers.
Health workers would make good subjects for a prophylaxis study if they don't have adequate PPE. If you're seeing health workers catch covid, have a randomly-selected set of them pop $4 of ivermectin once a week, give the rest placebo.
The Egypt prophylaxis trial was a pretty good model for testing prophylaxis with contacts. Its flaws were no placebo, no blinding, IIRC relying on clinical diagnoses instead of PCR tests with seemingly uninfected contacts, and the length of the study period. All easily fixed.
Contact people who test positive but don't (yet) need hospitalization, ask how many people they share their home with, then give randomly-assigned bottles of ivermectin or placebo accordingly. That would shed light on ivermectin's efficacy at stopping/slowing the advancement of disease, looking at the coved+ subjects, and also prophylaxis, looking at their household members. Follow up with phone calls at (?) monthly intervals: "Has anyone in your home come down with covid-19?" Maybe pay household members to come in for a test if they suspect covid. Maybe pay a randomly-selected subset to get tested at intervals, to catch those who are asymptomatic.
Prophylaxis will be much more easily tested if/when $1 home tests ("lick a stick") are widely available. A town could do it with school kids and their families. Give ivermectin to the families of a randomly-selected subset of school kids. Abbott (IIRC) has developed an app intended to serve as a "golden ticket" establishing that the person has taken a test within a specified time interval and shown negative. With permission of the tested (maybe permission being required if you want your kids in the public schools) that app could send test results to the town public health department. Instant study at very little additional cost. If an app like Abbott's isn't available or it's just unacceptable, use school attendance records to see how the kids fare, and make phone calls to the parents to check their covid status.
So far, 99% (1112 of 1127) trial subjects have shown prophylaxis. That's (?) 30% better than expected from the eventual vaccines. If ivermectin proved its efficacy, than many $billions for vaccines would be saved. Given what we understand about its several (possible) mechanisms, ivermectin could be effective against covid-24, which the currently under development vaccines might not touch.
What's the downside of a population taking ivermectin? Less itching (mites killed), worms gone (a problem for immigrants from places where worms are endemic), possibly less Lyme disease (weak evidence AFAIK) and less cancer (weaker evidence AFAIK). All upsides.
Safety is not a downside. Billion(s) have taken ivermectin, < 6-8 deaths over 20+ years. IMO ivermectin is arguably the safest drug known. NSAIDs kill 16,000 Americans a year. It's OTC and ivermectin isn't -- which is just WRONG, an unfortunate artifact of the FDA's (stupid IMO) policies.
Sorry for the wall of text. Did I make the point that RCTs for ivermectin are easy and worthwhile?
[-] movethroughit | 2 points
What I'd like to know is can Covid worsen without falling oxygen levels (SPo2, etc)? In that case, it should be simple to gauge Ivermectin efficacy if oxygen levels/requirements greatly improve or return to normal (as measured by SpO2 or Fi02) within 48 hours. This might well simplify trial requirements and result in more valid trials in less time. Adding consecutive negative PCR tests as an endpoint (maybe a secondary endpoint?)) would be useful, but of course will take more time.
[-] TrumpLyftAlles | 1 points
As far as I know (not very far), oxygen levels fall because lung cells are destroyed and also because the remaining intact alveoli are filled with gunk (not the right technical term) that interferes with oxygen exchange. That happens relative late in the course of the disease -- and often what drives people to seek medical help.
You probably know more about that than me. Fill in / correct me as needed.
My guess is that at stage, the best ivermectin can do with the low oxygen levels is stop further damage.
I think that guess is contradicted by some anecdotes, though. The Miami Herald article had the 45-year-old guy whose condition was deteriorating to the extent that he was on the verge of going onto the ventilator. A dose of IVM, another dose 12 hours later, and 24 hours after that the guy's symptoms were gone and he left the hospital. There's also the "brought back someone from the verge of death" story from the original Broward County news report. That person's O2 must have improved.
Anecdotes, though.
It's certainly an easy experiment to try. Create matched pairs of similarly inflicted patients, make random assignments, pass out ivermectin or placebo, and wait.
It's a great idea because as you say, it would be a nice short window, if it works.
I don't know whether there's another indicated therapy at that stage, could well be. That would create an ethical problem, using unproven ivermectin instead of the alternative therapy.
[-] Ok-Film-9049 | 1 points
I don't think you are contradicting yourself. IVM can act to reduce the microthrombi in the lungs, therefore allowing increased oxygen levels in body.
I am really hoping the IVM works and think it does at the latter stages. Wouldn't it be great if it was also an antiviral? the quickest way of proving prophylaxis as a concept is in animal models. By the time patients show up at hospital they might all be beyond the stage where the viral load is increasing.
You have pointed out the difficulties of human trials as a prophylaxis, however all the results look encouraging. I am sure the healthcare systems in developed countries ignore this research and think the lower income countries are just making it up.
professor thomas Borody was completely dismissed at a conference when he presented the finding that curing helicobactor (about 30 years ago) with a combination of cheap antibiotics would reduce ulcers. many of his peers wouldn't entertain the thought for a number of years. When his protocol was finally adopted it save millions of lives. the only conclusion you can draw is that many scientists cheat and therefore many research findings are ignored.
[-] TrumpLyftAlles | 1 points
When his protocol was finally adopted it save millions of lives. the only conclusion you can draw is that many scientists cheat and therefore many research findings are ignored.
What a huge achievement for Prof. Borody! So many lives saved.
My son has quoted one of his med school professors as saying that while the medical field is better than many, evidence-based medicine being a thing -- the actual practices change very slowly, mostly due to turn-over as docs retire and new docs replace them.
I mostly still write code like I did in the 80's. It's terrible by modern standards -- and I just don't care. ;)
[-] TrumpLyftAlles | 1 points
Wouldn't it be great if it was also an antiviral?
Stereomatch just posted this article where the researcher purports to have proven that ivermectin kills the virus.
[-] Ok-Film-9049 | 2 points
Many thanks, I have already commented on this thread. I said the only doubt i have is that some research is manipulated. Saying that, it is all looking positive so far. If the three studies run so far haven't been fiddled, this is proof to me.
[-] luisvel | 2 points | Sep 17 2020 04:21:12
Those are good ideas. It would be great to write them up as an academic comment with citations and distribute to MDs, researchers and people with influence in the public sector. I have been reading about alternatives to the RCT (actually, read top papers coming from that google search), and there are many good reasons to go with them; some similar to what you recommended here. Aside, I am in the US but born in Argentina, where many IVM trials are ongoing, so I may have reach to some researchers there.
permalink