Notes from the PDF of the trial protocol that TSN linked to. It's almost an introduction to how to design a study, to someone like me without experience designing a trial.

Succinct statement of ivermectin's action (the main theory courtesy of Monash)

Importin (IMP) α/β1 30 is a heterodimer that binds to the SARS-CoV-2 cargo protein and moves it into the nucleus which reduces the host cell antiviral response. Ivermectin destabilizes the Impα/β1 heterodimer, prevents it from viral protein binding and thus from entering the nucleus.

Interesting stuff about tetracyclines (one of which is doxycycline) and specifically DOXY.

Tetracyclines are highly lipophilic antibiotics that are known to chelate zinc component of matrix metalloprotienases(MMP)25. Corona viruses are known to rely heavily of 13 MMPs for survival, cell infiltration and replication, many of which have zinc as part of their MMP complex26. It may be possible that zinc chelating properties of tetracyclines may aid in inhibition of COVID 19 infection in humans. Some in vitro studies also suggested that tetracyclines may inhibit RNA replication on positive sense single stranded RNA viruses, like COVID 19.

Zinc seems to be understood as helpful with covid19, but is that actually established or just an implication of the HCQ/Zelenko stuff?

Second, teracyclines have well known anti-inflammatory effects. The anti-inflammatory mechanism of tetracyclines is complex and not fully understood. However, it probably involves inactivation of MMPs, serine proteases and decrease production of inflammatory cytokines such as TNF-alpha, interleukin beta and IL-6. It has been suggested that cytokines play an important role in the pathogenesis of COVID 19 including exacerbation of lung damage. Several authors have suggested that tetracyclines may be used to treat inflammatory disorders including those caused by Corona viruses.

Anti-inflammatory!

Third, as they are highly lipophilic drugs, tetracycline has good tissue penetration in the lungs. This, along with their anti- inflammatory properties, might allow them to inhibit viral replication in the lung and reduce lung damage. The recommendation of using tetracyclines as treatment for Corona virus was previously suggested given that chemically modified tetracycline can prevent septic shock induced by ARDS.

Based on the evidences, Mohit Sodhi et Al strongly urged international research groups to consider investigating the potential therapeutic efficacy of tetracycline in treating COVID 19.

Compared with the original tetracycline, the synthetics, including minocycline and doxycycline, show a better pharmacokinetic profile than the first-generation tetracyclines when used orally, being rapidly and completely absorbed, even in elderly populations, with a longer half-life and excellent tissue penetration, with almost complete bioavailability.

The rationale of using combination of ivermectin and doxycycline for treatment of COVID 19 is based on their antiviral and anti-inflammatory properties. Since the two drugs have different mode of action, their synergistic effect would be of value to contain the viral infection by targeting different sites of the pathogenesis of the disease.

Standard care: both the experimental and placebo will receive the available standard of care, like

Paracetamol, Antihistamine, Cough suppressant, Vitamins
Oxygen therapy according to indication and need
Low molecular weight heparin according to indication
Appropriate other broad spectrum antibiotics
* Other drugs for associated co- morbid condition

Paracetamol = acetaminophen = Tylenol

Management of the adverse events:

Drugs adverse effect will be monitored by a defined committee. The patient experiencing adverse effect of the drugs will be discontinued from the study. It will be managed with priority to the highest possible level by the hospital authority as well as the investigators.

If the patient progresses from mild to moderate or severe disease, the study will be continued and available management of the appropriate severity will be immediately started. The patient will be monitored closely.

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I'm getting pissed off by arrogant comments like the one below. Instead of pointing out what precisely he thinks is lacking in the study, he uses disputable vague assessment ("poorly described"!?) and prejudiced etiquettes such as "third world".

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No, a poorly described, retrospectively registered, single-center, third world-conducted RCT with a per protocol analysis, completely nonstandard endpoints and 360 patients is not enough. That's the unfortunate reality of it. I want it to work (or rather, I want anything to work), but I've seen far too many crap trials fail to think this is any different - the default setting in clinical evidence appraisal is cynicism for a reason. Safety has not been demonstrated in COVID patients. It's got cheap going for it, which is great. The rest, not so much.

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