Auszug aus Euronews 24.3. 2020: Kann Chloroquin Covid-19 Patienten retten?
Das Medikament war in Marseille an einem Institut eines Universitätskrankenhauses zur Behandlung von 24 Personen mit Covid-19 eingesetzt worden, und die vorläufigen Ergebnisse dieser Studie wurden am 20. März im International Journal of Antimicrobial Agents veröffentlicht.
In der Studie kam man zu dem Schluss, dass die Behandlung mit einer Art Chloroquin (Hydroxychloroquin) und einem Antibiotikum trotz der geringen Stichprobengröße bei mehreren Patienten eine "Reduktion/Verschwinden" des Virus zeigte.
"Nach sechs Tagen gab es einen sehr signifikanten Unterschied zwischen denen, die behandelt wurden, und denen, die nicht behandelt wurden", sagte der Experte für Infektionskrankheiten Didier Raoult, der das Institut in Marseille leitet, wo die kleine Studie durchgeführt wurde. Der Zustand von 75 Prozent der Patienten mit der Behandlung habe sich verbessert.
Bei eingen Patienten habe man innerhalb von 48 Stunden eine signifikante Verbesserung verzeichnet. Das Institut des Universitätsklinikums will jetzt alle Patienten, die eingeliefert werden, mit der medikamentösen Therapie behandeln.
Allerdings finden viele andere Experten es zu früh, um zu sagen, ob das Medikament wirksam ist.
"Dies ist nicht die erste Epidemie eines Virus, bei der wir [ein Zeichen] der Hoffnung auf eine Behandlung haben, und es stellt sich heraus, dass es doch nicht funktioniert. Die Hoffnung reicht mir heute aus, um alles zu tun, damit wir überprüfen können, ob das Medikament wirkt oder nicht", sagte Frankreichs Gesundheitsminister Véran.
...
"Niemand in der medizinischen Welt sagt, dass Professor Raoult mit der Annahme falsch liegt, dass Chloroquin eine wirksame Behandlung gegen das Coronavirus sein kann, aber die Medizin wird nicht durch Veröffentlichungen [in den Medien] praktiziert, sie wird nicht auf der Grundlage einer Studie mit 24 Patienten praktiziert", sagte Michel Cymes, Chirurg und französischer medizinischer Kommentator in einem Interview mit RTL.
Die französischen Forscher unterstrichen die dringende Notwendigkeit, eine Behandlungen zu finden.
"Es besteht ein dringender Bedarf an einer wirksamen Behandlung, um symptomatische Patienten zu behandeln, aber auch um die Dauer der Virusübertragung zu verringern, und so die Übertragung in der Gemeinschaft zu begrenzen", schrieben die Ärzte in Marseille.
US-Präsident Donald Trump geriet kürzlich in die Kritik, weil er erklärte, dass das Medikament wirksam sei und in den Vereinigten Staaten zugelassen werden solle.
Das Medikament wurde auch in Labors in China untersucht und ist derzeit Gegenstand einer randomisierten Studie der Universität von Minnesota mit 1.500 Teilnehmern, um herauszufinden, ob es wirksam ist.
Viele Wissenschaftler sind allerdings der Meinung, dass mehr Forschung zu diesem Thema erforderlich ist.
Auszug aus Robert Zaretsky: The source of the hopes for a coronavirus cure should raise a lot of red flags.
Trump may not be aware that the hydroxychloroquine hype is French in origin. The researcher responsible for the “molécule miracle” is Didier Raoult. The founder and director of Institut Hospitalo-Universitaire, or IHU, in Marseille, the 68-year-old Raoult has compiled a sometimes dazzling, sometimes disturbing career that could have been scripted by Marcel Pagnol or Honoré de Balzac. Born in Senegal, Raoult defied his father, who was serving there as a military doctor, and quit high school in his junior year. Signing up with the French merchant marine, the young Raoult spent the next two years at sea. Returning to France, he graduated from medical school and nimbly made his way in both the political and professional worlds. Not only did he become an internationally recognized researcher, but he was also a nationally recognized power player. Cultivating politicians as carefully as he did petri dishes, Raoult overcame the opposition of older research institutions and, with the support of then-President Nicolas Sarkozy, created the IHU 10 years ago. Despite the doubts, Raoult’s work on infectious disease earned him a place on the French government’s COVID-19 commission.
Not surprisingly, Raoult’s rapid rise raised as many eyebrows as huzzahs. While his fans applaud the 3,000 scientific articles Raoult has co-signed, his critics argue that these staggering numbers do not add up. Do the math, they remark, and it turns out the Marseillais researcher publishes more papers in a month than most productive researchers publish in a career. Raoult’s method, according to one critic, is to task a young researcher at IHU with an experiment, then co-sign the piece before it is submitted to publication. “Raoult is thus able to reach this absolutely insane number of publications every year,” according to one anonymous source quoted by the site Mediapart. More disturbingly, the critic added, “it is simply impossible for Raoult to verify all of these papers.”
Indeed, the question of verification hovers over Raoult’s clinical trial on the effects of hydroxychloroquine on the novel coronavirus. Combining a regimen of Plaquenil —the commercial name of hydroxychloroquine — and an antibiotic, Raoult treated 24 patients at IHU in early March who had tested positive for COVID-19. After six days, the virus had vacated the bodies of three-quarters of those same patients. On March 16, Raoult announced the results not in a scientific journal but in a YouTube video, in which he declared the jig was up for the virus. Predictably, his self-proclaimed victory then ignited the hysteria that has since swept the world and reached as far as the Oval Office.
In France, pharmacies have been overwhelmed by demands for Plaquenil, leading one pharmacist quoted by Le Monde to exclaim: “Perhaps Raoult is right, but instead of taking the time to carry out a serious study, he has given us two months of theatrics.” Critics argue that not only were there too few subjects in the chloroquine study, but that some of them dropped out during the trial, potentially skewing the results. In addition, Raoult has not released the raw data from the trial, which, remarkably, was not double-blinded. According to Dominique Costagliola, chief epidemiologist at the Pasteur Institute, the trial was so slapdash that “it is impossible to interpret the described result as being attributable to the hydroxychloroquine treatment.”
Auszug aus Molina et al.: No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection.
Auszug aus Science Integrity Digest: Thoughts on the Gautret et al. paper about Hydroxychloroquine and Azithromycin treatment of COVID-19 infections
The patients were recruited at different “centers”, but it is not very clear which patient was located in which hospital. The HQ treated patients were all in Marseille, while the controls were located in Marseille or other centers. One can imagine that hospitals might differ in treatment plans, ward layouts, availability of staff, disinfection routines, etc. It is not clear if controls and treated patients were all recruited and treated at the same hospital?
Although the study started with 26 patients in the HQ or HQ+AZ group, data from only 20 treated patients are given, because not all patients completed the 6-day study. The data for these 20 patients looks incredibly nice; especially the patients who were given both medications all recovered very fast.
What happened to the other six treated patients? Why did they drop out of the study? Three of them were transferred to the intensive care unit (presumably because they got sicker) and 1 died. The other two patients were either too nauseous and stopped the medication, or left the hospital (which might be a sign they felt much better).
So 4 of the 26 treated patients were actually not recovering at all. It seems a bit strange to leave these 4 patients who got worse or who died out of the study, just on the basis that they stopped taking the medication (which is pretty difficult once the patient is dead). As several people wrote sarcastically on Twitter: My results always look amazing if I leave out the patients who died, or the experiments that did not work.
Auszug aus einem post-publication review von Frits Rosendaal
The index group and control group were drawn from different centres. The information that is given about characteristics of index group and control group is minimal, and still major differences are evident from all three variables shown (age, sex, presence of symptoms). The authors have performed statistical tests on these baseline characteristics, which is inappropriate. In the text they emphasise the absence of statistically significant differences between groups, implying that absence of statistical significance proves equality, which shows a lack of understanding of basic statistics.
It is remarkable that in a randomised trial, when only chance may have introduced differences between groups, authors go out of their way to present a long list of baseline characteristics to lend credibility to the fairness of comparing outcome occurrence between groups, where here, in a non-randomised comparison of patients from different centres who clearly do differ, authors have not made the slightest effort to present such baseline characteristics. The reviewer can only come to the conclusion that the comparison with the control group is meaningless.
It is reported that 42 patients met the eligibility criteria, and of these 16 were in the control group, and 26 in the treated group. Of these 26, six were excluded (and incorrectly labelled as lost to follow-up): three were transferred to the ICU, one died, and two terminated treatment or were discharged. Firstly, it is noteworthy that 4/26 treated patients deteriorated and 0/16 control patients, which emphasises that the groups were different. More importantly, excluding patients who deteriorated from the analyses introduces severe selection bias, since it selectively excludes people who did not do well (as an extreme example: if 25/26 treated patients had died, and one had virus clearance at day 6, would a claim of 100% clearance be valid?).
Auszug aus NDR: Drosten kritisiert Chloroquin-Studie:
Auszug aus Toumi & Aballea: Commentary on “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open label non-randomized clinical trial” by Gautret et al.
Auszug aus: Expressis-Verbis: Professor Didier Raoult, Sinnbild eines Widerstands französischer Prägung
https://yetiblog.org/archives/31470