While we publish an article on the shortcomings, omissions and manipulations of the great trial british Recovery of Oxford University, a press release out yesterday, claiming a “discovery” : the corticosteroid Dexamethasone would improve the probability of survival among patients who received ventilatory assistance. This information has of course been the subject to this moment many times in the media.
A doctor told us : The corticosteroids are used for a long time in respiratory distress. It would seem so abnormal that it does not administer to a patient in an advanced state of distress.
What is the Dexamethasone ?
It is a corticosteroid whose properties are well known and documented in the Vidal, as well as in numerous publications and studies.
It is a corticosteroid could not be more banal, anti-inflammatory drug, which is already used for the treatment of the COVID-19 in advanced stages of the disease. Corticosteroid less potent, methylprednisolone, is in fact used also in the treatment protocol for MATH+ developed by the Eastern Virginia Medical Group.
Under respiratory assistance, patients have a decrease in their capacity of the respiratory system and it is therefore not surprising that a steroid works at this level.
What is more surprising is why this news is coming now
In the release date of this June 16, 2020, the researchers write that the observations have been made as of the date of the June 8, 2020.
Hydroxychloroquine, however, has been the subject of a press release immediately which concluded its withdrawal in date of June 5, 2020. The Pr Landray told us that the analyses had been made the day before (so June 4, at the request of the MHRA). To this date, the control group included 3132 patients. Less than 24 hours have been necessary for the investigators to do a press release and inform them of the removal of trials of hydroxychloroquine on the ground that it showed no advantage, but was not toxic. As a reminder, the case-fatality rate observed was 25% and is not different from the placebo.
Small return on the calendar
- On march 23, a request is made to the MHRA by the study investigators Recovery, Pr. Horby and Pr Landray. Two days later, the acceptance of the inclusion of hydroxychloroquine in the test is given either on the 25th of march.
- A presentation document of hydroxychloroquine is drafted on the 1st of April 2020. This document is no longer available on the website. It has been replaced by a version 3, 18 April 2020 even if the name of this document has a different date and includes the 20 April
Information Fact Sheet for Hydroxychloroquine – FranceSoir
- On may 26, the regulator gives permission to use the remdésivir for the Covid 19.
- On may 27, Recovery includes the remdésivir in the test without changing the protocol.
- On June 3, Recovery a modification of its protocol, which makes it pass 6 arm 7 arm with multiple items amending.
- On June 4, the regulator request for Recovery of check the effects of hydroxychloroquine.
- On June 5, Recovery, in a press release, without qualification, declares that the hydroxychloroquine, non-toxic, has no effect on the Covid 19 and out of the test with immediate effect.
- On June 5, FranceSoir interview Martin Landray.
- On 6 June, the interview of Martin Landray is published and FranceSoir out a first article questioning Recovery on the assay used, and other elements.
- On June 8, Recovery done the analysis on the dexamethasone. We do not learn this information until 16 June via the press release. No one was aware.
- June 15, FranceSoir, has published an article to support questioning the lies and manipulations regarding Recovery.
- On June 16, Recovery informs to a large pump that dexamethasone reduced mortality. The day after the charges are severe, as revealed in our article.
We will not return to the diversion made by an article of Liberation interposed, where the investigators of Recovery indicated that FranceSoir had reported a wrong comment or misunderstood. This same person announced on twitter, about the study flawed, the Lancet, finally, a study showed that hydroxychloroquine does not work, before having to engage in an exercise of style to recover the kick. It is a shame for a journalist, that wants to be scientific, not only do not have not flushed the enormous fraud of the Lancet, and in addition to miss the elements “alarming” study of Recovery.
They have obviously used the deal offered by way of the media interposed with an interview in Liberation. Before, of course, to declare that the about Pr Landray, as we had reported, were in fact correct.
But it is not the purpose, we have doubts about the Recovery, we have written, but some elements jump in the face even of the less informed. Why wait 8 days to announce a good news, then, that for an information against the hydroxychloroquine investigators rush to the social networks.
Looking more closely at the protocol, first of all. This protocol is version 6 dated may 14, 2020. This excessive number of version is the sign of a lack of scientific control is clear evidence of a protocol that will work at cross purposes, at the discretion of the political needs of the moment. An internet-based tool allows you to make a comparison with the previous version. For non-English speakers, we recommend that you make a right click in the browser and use the translation service this allows to have a translation.
In red the elements removed, and in green the elements added. In addition, the study moves to a 7 arm with a new arm, the “convalescent plasma” and there has been a change from a test in “parallel” to a test “factorial” with randomisations different
Recovery Protocol – FranceSoir
The 7th arm is the arm of plasma that was not included in the previous version. This means that patients will be able to receive the plasma of patients who are cured.
Recovery Protocol – FranceSoir
In addition we see that the need for renal replacement (dialysis) is moved to secondary measures to other measures and what is included in a composite measure of mortality or the need for ventilation. We will return to the importance of this point in a future article.
Recovery Protocol – FranceSoir
It is normal that a study on the evolutionary path protocol to move with the times.
By focusing more closely to the available data, several issues challenge us.
We are in the midst of the epidemic and hospitalizations are declining, however they are much more important in Britain than in France at the same stage of the epidemic.
On 5 June, so the day after the analysis of the data for HCQ, the basis of the control cell “SOC : standard of care” brought together 3132 patients. On June 8, during the analysis depending on the SOC, there were 4321 ; a difference so of 1189 patients. These two dates, the number of patients reported in the trial was of 11000 patients on June 5 and 11500 patients on 8 June, approximately what said Recovery in the releases of the two respective dates.
Between the June 5, 515 admissions to the hospital, June 6, 438, 7 June 435 and the June 8, 458 or 1846 patients new hospitals in the United Kingdom. The previous rate of inclusion in the trial, estimated by Recovery was 13%; this means that they would have included 1846*13% = 239 patients. However, the press release said that the delta of the inclusion and of the order of 500. Recovery has therefore had to push for the inclusion of patients in the trial. Ithese the most questionable is how can we have an increase of the inclusion of 500 patients (the difference between 11 500 on June 8 and 11, 000 5 June) and at the same time an increase in the placebo group of 1189 (4321 the 8th of June at 3132 5 June).
Let’s go back to the sheet of the presentation to the participating physicians on hydroxychloroquine
The current version on the site is the version 3 of the April 20, 2020, or after the date indicated by the ‘ properties of the document of 18 April 2020, a discrepancy of more. Little important. But it is important that this document is the justification of the administration of the dosage of hydroxychloroquine, the 2400mg the first 24 hours, followed by 800mg the following days for 9 days. This document has 3 pages and explains that they are based on a population pharmacokinetic analysis and a WHO document of 1995 on the use of chloroquine to set the dosage. However, the pharmacokinetic analysis is not available, the one evoked by the Pr Landray and which would form the basis of the assay is very high hydroxychloroquine.
Impossible to find version 2 on the site of Recovery. Our requests for Recovery were in vain. However, we have managed to get version 2 of this document as well as the WHO report (70 pages), which we have presented to various experts, microbiologists, and doctors. Without going into the detail of the analysis, the first items that stand out are :
Version 2 Information Fact Sheet -FranceSoir
- This document here, is 25 pages and includes the famous analysis of pharmacokinetics, which has been removed from version 3, document which for memory has been reduced to 3 pages. Why?
- The pharmacokinetic analysis of these documents extrapolate several things : chloroquine and hydroxychloroquine, the extrapolation of the loading dose based on the WHO document.
- One may ask the question whether these experts have not confused the units or metrics.
Our experts looking at the information are even more surprised of the amounts of hydroxychloroquine discussed and prescribed. Hydroxychloroquine has a long half-life in patients already infected, and the lethal dose is considered to be between 3000mg and 5000mg knowing that the overdose is from 2000mg as defined in the Vidal with prescription of hospitalization in the emergency room. The WHO document reports of doses potentially lethal to 50 mg/Kg. Patients received 2400mg the first day, 800mg the second 800mg the 3rd and so on, until the 9th day. The pharmacokinetic data presented in the supporting document on the determination of HCQ in Recovery are the result of extrapolations and theoretical simulations which do not have their place in such a document , where only the experimental evidence must prevail.
Our expert clinical trial we said :
This is a serious fault could explain the lack of benefit of HCQ which is believed to have killed as many patients as it saved.
Data extracted from the product monograph for hydroxychloroquine labs Mylan Pharmaceuticals
Fatal Dose of HCQ – FranceSoir
Author(s): The Citizens ‘ group for FranceSoir