Ivermectin vs Combined Hydroxychloroquine and Antiretroviral Drugs (ART) Among Asymptomatic COVID-19 (Thailand, 2020-06-17)

[-] TrumpLyftAlles | 2 points | Jun 17 2020 17:49:31

The first clinical trial out of Thailand! This brings the ClinicalTrials count to 26. With 3 in the EU equivalent of ClinicalTrials, 5 Indian trials, and a handful elsewhere (Lebanon, 2 at Iran, ??) there are almost 40 trials underway (2 are "completed" but haven't reported results yet).

Official title: Comparative Efficacy of Ivermectin Versus Combination of Hydroxychloroquine Plus Darunavir/ Ritonavir for Shortening Duration of SARS-CoV2 Detection From Respiratory Secretion Among Asymptomatic or Afebrile COVID-19 Infection

Description:

* Study procedure will be carried out after informed consent is obtained.

* Baseline physical exam and laboratory investigations will be performed.

* Eligible patients will be randomized to one of the two treatment arms.

* Symptoms and signs will be monitored daily.

* NP swab will be done at day 5-7, and approximately weeky until discharge.

* Weekly complete blood counts, blood chemistries, electrocardiography will be performed for adverse event monitoring.

* Patients will be discharged at 2- 4 weeks after hospitalization, according to PCR results.

* There will be 1-2 follow up visit at out patient clinic for NP swab (patients with +ve last NP swab before discharge), and blood tests.

* Additional 5-8 ml. of EDTA blood will be taken at baseline and weekly for antibody detection.

* Interim analysis of both safety and efficacy will be performed when approximately 50% of enrollment is achieved.

* Intention to treat analysis is planned at the completion of enrollment.

EDTA stands for Ethylenediaminetetraacetic acid. EDTA functions by binding calcium in the blood and keeping the blood from clotting. ... The nominal EDTA concentration is 1.8mg EDTA per milliliter of blood.

This is an interventional study with N = 80, randomized into two arms.

Masking: Single (Outcomes Assessor)

Masking Description: PCR for SAR-CoV2 detection will be performed by technician without knowledge of treatment arm

Primary Completion Date: June 2021 (???)

Experimental arm: oral ivermectin 600 mcg/kg/day once daily for 3 days

Control arm:

Day 1 400mcg hydroxychloroquine, 200mg HCQ on days 2-5
Darunavir/ritonavir (400/100mg) every 12 hours for 5 days

Primary outcome measures:

Adverse event rates [Time frame: after first dose until day 28 of follow-up]
Efficacy for shortening duration of SAR-CoV2 detection by PCR [ Time Frame: weekly after treatment until 4th week ]

Secondary outcome measure:

Antibody detection rates [ Time Frame: weekly after treatment until 4th week ]
comparison of median duration for total antibody detection in each arm

Thoughts:

It's interesting that HCQ is being compared to ivermectin; HCQ seems to be of declining interest after several negative results, including the WHO recently inveighing against its use. HCQ fanboys advocate HCQ + AZT + Zinc; they will reject this study's results because it doesn't conform to that (AFAIK no-scientific-basis) belief.

HCQ vs ivermectin will be useful for everyone else, though, i.e. those who are not HCQ True Believers.

These drugs in the control arm are new to me. HIV drugs? Why?

Darunavir/ritonavir:

Darunavir is used with ritonavir (Norvir) and other medications to treat human immunodeficiency virus (HIV) infection in adults and children 3 years of age and older. Darunavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although darunavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of transmitting the HIV virus to other people.

From [wikipedia](https://en.wikipedia.org/wiki/Ritonavir#:~:text=Ritonavir%20(RTV)%2C%20sold%20under,used%20with%20other%20protease%20inhibitors.):

Ritonavir (RTV), sold under the trade name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Often a low dose is used with other protease inhibitors.

There are 10 trials looking at Darunavir + covid-19, so it's not a weird idea.

There are 79 trials looking at ritonavir + covid-19!

600mcg/kg of ivermectin for three consecutive days is the heaviest dose of any trial, IIRC: 2 studies are doing one dose of 600 mcg, and the new Israeli trial is dosing a total of 600 mcg over the course of 3 days. 1800 mcg approaches the 2000 mcg dose that was found to be safe by the Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects study:

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 design seems fine. N = 72 is OK, less than the trial average ~= 100. The limited masking may be adequate. The weekly blood chemistry tests (including EDTA) is interesting, esp. given that the study is not looking at any anti-coagulants (AFAIK). HCQ suppresses the immune system; maybe that can help with the too-much-coagulation problem?

The huge problem with this study are the completion dates, primary 2021-06 a year from now and study completion 2020-11-21. By that date, hopefully much of the world will have been vaccinated against covid-19, making this study moot. Let's assume the dates are wrong.

Also posted to /r/covid19.