A hint on the CoVer - Ivermectina Italian trial

DesinasIneptire | 14 points | Dec 27 2020 18:53:52

A hint on the CoVer - Ivermectina Italian trial

This is the machine translation (by the site deepl dot com) of a an article published on the website of a local newspaper on December 21st. The original article is in https://www.lasicilia.it/news/covid-19/380277/covid-cacopardo-ho-avviato-la-profilassi-con-ivermectina-risultati-fra-una-settimana.html

Catania - "On Saturday I started the administration of Ivermectin on one patient. Then today I will proceed with a second patient and finally to follow on a third". This was confirmed yesterday by the professor of infectious diseases and head of the department of Garibaldi Nesima, Bruno Cacopardo. The professor explained that all three patients undergoing prophylaxis with the drug that treats strongyloides, all have pneumonia to a degree already severe, and may be liable to an aggravation up to the intensive care unit. "At this point - explained the professor - within a week we will be able to see the first effects of the treatment on which a large group of experts have high hopes". "In the meantime - added the professor - in recent days I have made contact with other groups of doctors both Italian and foreign who are treating patients with the same model of prophylaxis. Doctor Bisoffi, from the hospital of Negrar, near Verona - one of the areas currently most affected by the second wave of Covid, claimed that he is having good results with the Ivermectin treatment. He only added that he needs to develop data in his possession".

"From the international point of view - added the professor - in some regions of South America, particularly Peru, Paraguay and Mexico and specifically Ciapas has been made a mass distribution of Ivermectin to act against Larva migrans which is a parasite. And this mass distribution, just look at the data of the results, are striking. This blanket administration in fact coincided with a dramatic reduction in the number of cases and deaths from Covid compared to other regions of the same nation".

So in your opinion this represents a very accurate signal?

"Absolutely so. In fact, people in these regions do get Covid, but because they are treated with Ivermectin they don't have complications and they recover without problems."

Regarding the slow but continuous decline of the epidemic curve, what do you expect, especially in Catania, a city where the cases are greater than any other found on the island?

"Catania, I don't want to seem a catastrophist, has not respected the deliveries. When there is an epidemic and pandemic event, if only for the spirit of solidarity towards the fragile subjects that one has even within his own home (grandparents, uncles, the same parents maybe sick and made fragile by co-morbidities) the citizens for respect should have contained certain attitudes. Instead, a few days ago to go to the center Garibaldi I made a detour and I passed by the parts of Corso Sicilia, I realized that people do not even use the mask and if they use it clumsily, as a useless frill, put under the nose or put to cover only one side of the mouth. Truly this attitude, combined with the confusion that is around, dictated by the Christmas frenzy, seems to me a scenario at least imprudent and, however, of little respect for both medical professionals who every day fight against this terrible disease and for the fragile subjects.

But what signals does the curve give you?

After an initial phase of marked descent, once the peak was reached it slowed down dramatically. But this slowdown is due to the fact that there is still circulation of the virus, there are still contagions. And my concern, clearly, is not about what is happening now or what will happen. By now the downward attitude of the curve is spontaneous, even without measures it would go down slowly. The problem is what could happen soon because of the Christmas gatherings, because in fact the restrictions will begin with the red zone on December 24 and people are anticipating the Christmas shopping rush. In short, this is not good. I think that for a year, just one year, then the vaccine will come and the curve will go towards a spontaneous reduction, you can also think of spending a Christmas more gracious, more sober or not?".

Absolutely, maybe move the holidays up a few months?

"We needed to spend these holidays soberly because we don't know if this euphoria will pay off later. Instead we should have accelerated the downward attitude of the curve that is proceeding too slowly because of these behaviors. Now I don't want to say that these are incorrect attitudes, but certainly imprudent".

Do you think we'll get out of this just with the vaccine or even sooner?

"Three episodes are coming that will change the story of the disease. The first one is the vaccination that done extensively will produce its effects within two, three months. The other positive issue is the monoclonal antibodies that are arriving in Italy and there was no reason not to have them because they are really a possible panacea to the progression of the disease, however expensive. And thirdly we will have a spontaneous downward trend of the epidemic curve that I trust for reasons related to the higher circulation of the virus more than we can intercept that spontaneously will tend to descend. These three components will help us and I think that between April and May we will be out of the pandemic and we will finally get back together".

So professor in a week we will know if the Ivermectin treatment has yielded the desired results?

"Our new appointment is pushed back a week....".

Apart from the cases treated by prof. Cacopardo, which is a very respected clinician, here the notable part is the one evidenced in bold, concerning prof. Bisoffi from the hospital of Negrar, because in Negrar there is an ongoing preregistered trial of ivermectin, the only one enlisted by the Italian regulatory agency AIFA. The protocol is in https://www.aifa.gov.it/documents/20142/1201058/COVER_ivermectina_documenti.zip?download=true.

This is the first hint I saw about what's happening there (I also asked to a friend working for the regulatory agency, and as expected he didn't give me any answer).

"Good results"; can't wait to see them.

[-] bikes4paul | 4 points | Dec 27 2020 21:31:16

I've been very anxiously awaiting their results! They are trialing much higher doses of IVM 600mcg/kg 5 days vs 1200mcg/kg 5 days. That's the highest I've seen used to date for C19. Since IVM has such a high safety margin (tested at 2000mcg/kg with no increase in AEs) I've thought that the low dosing being used is missing a significant dose response relationship in C19. Their trial is scheduled to be completed this month so I'm hoping we'll see their results in the next couple weeks.

[-] TrumpLyftAlles | 2 points | Dec 27 2020 22:17:22

I can't find the results just now -- but I wrote code to see what the blood level of ivermectin would reach after dosing at 1200mcg/kg for 5 days, based on the 18-hour half-life (Merck's estimate). It topped out at 1994 -- barely shy of the 2000mcg/kg that Guzzo found safe. I wonder if they did the same math when coming up with their protocol?!

[-] bikes4paul | 2 points | Dec 27 2020 22:43:10

Very interesting calculation and question. It does seem like an unlikely coincidence to be that close in concentrations. Even the 600mcg/kg at 5 days is so much higher than what most are prescribing in the US (when you can convince a physician to prescribe at all). Most often it's the 200mcg/kg single or double dose. The single is much too low for an acute infection IMO. I think it's fine for prophy. Hopefully, the results of this Italian study will provide evidence to change dosing guidelines. Argentina has already established that higher dosing is tolerated well and yielded excellent results.

[-] TrumpLyftAlles | 2 points | Dec 27 2020 22:48:31

My brain isn't big enough to do a proper gestalt analysis of the trials to date -- so I can only wonder if there is data supporting spacing out the doses. We've seen days 1 and 3, and another dose a week later. Maybe days 1, 3, 5, 7, 9 would be better than 5 days in a row?

I don't think we'll ever know.