1) Dose is too low. Would recommend 200mcg/kg. 2) Power is too low to see a difference in mild to moderate disease. Need to increase n.

permalink

This trial is sponsored with Sheba Medical Center in Israel.

Brief Summary:

Ivermectin which is an FDA-approved broad spectrum anti-parasitic agent, has also anti-viral activity. In vitro study have shown its activity against SARS-CoV-2, however its clinical effect on patients with COVID-19 never been tested.

In this RCT we would like to evaluate the effect of Ivermectin on reduction of viral shedding among mild to moderate COVID-19 patients, and in shortening the symptom resolution time.

Official Title: Ivermectin vs. Placebo for the Treatment of Patients With Mild to Moderate COVID-19 to Prevent Progression to Severe Infection and to Decrease Viral Shedding - A Double Blind , Randomized Controlled Trial

This is a double-blind RCT with N=100.

The experimental arm will receive one 3mg dose. The control arm will get placebo.

Primary outcome measures:

• Viral clearance at day 6
• Shedding period: time between first PCR positive test to last of two consecutive negative tests
• Days until symptoms clear (with a 14-day time frame)

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Subject age: 18 - 80

This trial is for patients who do not have severe infection -- severe defined as requiring ventilator support (invasive or non-invasive).

Start date: 2020-05-12 Primary completion date: 2020-09-30 Study completion date: 2020-10-31

Thoughts:

It's good that ivermectin alone is being investigated; it's more common to evaluate IVM + (something else). Since there are just two arms, N=100 seems adequate, depending on the size of the hoped-for benefit from the drug.

The dose is disappointingly low, either the lowest being trialed, or a tie with a study or two. That's ridiculous, given ivermectin's superb safety record; 10 times the usual 200mcg/kg has been tested and shown safe.

AFAIK, this is the first ivermectin study out of Israel. If the study shows positive results, that might have greater weight in Western circles than results out of Egypt or Argentina.

The September / October completion dates are shortly before the predicted second wave will occur in North America and Europe, if in fact there's a seasonal effect with covid19.

permalink

Good news: the dose is higher than I inferred from the ClinicalTrials description.

It is 12-15mg/day, based on the patient weight, given on 3 consecutive days, which results in a cumulative dose of 600mcg/day. Excellent!

---

Here is my exercise in hubris, trying to tell a couple of pros how to do their study. I can be really dumb sometimes.

Yesterday I send the two researchers identified at ClinicalTrials this email:

Hi, Doctors Schwartz and Biber,

I hope I misunderstood when I read about your forthcoming study on ClinicalTrials.gov: Is it your intention to give only 3mg of ivermectin to your experimental subjects?

I'm sure you know that the usual FDA-recommended dose is 200mcg/kg, which corresponds to 44mg for a 220-pounder like me!

This paper Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects says:

The primary safety endpoint was mydriasis, accurately quantitated by pupillometry. Ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-approved dose of 200 microg/kg.

The trial Ivermectin Effect on SARS-CoV-2 Replication in Patients With COVID-19 is treating at 600mcg/kg.

I am a self-appointed ivermectin enthusiast on reddit, and wrote up your design briefly here. It is an excellent design, good N, beautifully blinded. It has a chance of being very persuasive, making a big difference.

But not if you're only giving patients 3mg. You'll report that ivermectin did not clear COVID-19 by day 6, and did not reduce the period that patients were shedding the virus -- not because ivermectin doesn't work but because you didn't test the therapeutic dose. Arguably ivermectin is the safest drug known: billions of doses given to billion(s) of people with an outstanding safety record. There's no downside to dosing higher!

Please give a higher dose of ivermectin. 600mcg/kg would be good!

If I misunderstand, please clarify your dosing regimen on ClinicalTrials.

Thanks for doing this research! Hopefully it will help identify ivermectin as truly helpful against COVID-19.

Today I got this reply: they are dosing at 600mcg/kg, which is great, except I think they did the math wrong?!

Thanks for your comment.

We are using the 3mg capsules.

The dose is 12-15mg/day (according to body weight) and we are giving it

for 3 consecutive days. (around 600 mcg/Kg).

BW

So I sent them this just now (this is really dumb, because I failed to realize that they mean 600mcg/kg cumulatively instead of 600/kg each day):

Thanks so much for your reply, Professor Schwartz!

I might be wrong (I'm not the MD and your credentials are impeccable) but it seems like your dose is low if you're aiming for 600mcg/kg (which is EXCELLENT).

From this site, the calculated dose should be a lot higher than 12-15 mg.

More like 40 mg?!! That would be 13 capsules for a 68kg patient.

Forgive me if I'm an idiot and/or I'm stepping on toes. Just trying to be helpful.

I think your study is going to have a very large impact! I guess you saw the super-laudatory article on TrialSiteNews? Everyone will pay close attention when your trial is published. Could make a big difference!

Fingers crossed that ivermectin works in your trial.

Thanks very much for the reply!

68kg = 150 pounds, which I selected as a guess at average patient weight.

The study's entry at ClinicalTrials.gov still says:

Drug: Ivermectin Oral Product
3mg Capsules

Edit: While I was posting about this on \r\covid19, I realized that the cumulative dose of 12-15mg over three days adds up to about 600mcg/kg. So I send this email.

UGH! Sorry! Apologies!

Your 12-15 mg/day over three days accumulates to 600mcg/day.

Sorry for misunderstanding, and trying to teach the teachers. I'm an idiot.

Thanks for this study!

permalink

An article about the study where one of the researchers is interviewed. Doesn't add much.

The antiparasitic drug Ivermectin could "cure" the coronavirus, according to an Israeli scientist

Wow, it could "cure"? So could everything else. Sensationalism.

This is discouraging:

He told the Post that the study is underway due to bureaucratic delays from the Ministry of Health. But he added that he expects the study to be complete in the coming months, assuming enough people enroll.

It will be a bummer if a bunch of ivermectin trials never happen because the pandemic ends too soon.

permalink