The 27th ivermectin vs covid-19 trial on ClinicalTrials.gov, the first trial out of Italy! Do they still have people catching the virus in Italy??? Also Spain: The study will also be be done at a couple Spanish hospitals. The primary sponsor is at an Italian hospital.

Official title: Randomized, Double-blind, Multi Centre Phase II, Proof of Concept, Dose Finding Clinical Trial on Ivermectin for the Early Treatment of COVID-19

1. Description:

Primary objectives

The study is aimed:

1. at defining if ivermectin, administered at dosage of 600 μg/kg or 1200 μg/kg QD for five consecutive days is safe in patients with initial, asymptomatic or oligosymptomatic SARS_CoV-2 infection,

2. at defining if ivermectin, administered at the dosage(s) found to be safe decreases the viral load of SARS-CoV-2 at Day 7.

Secondary objectives To assess

1. the temporal profile of viral load at baseline, day 7, 14 and 30
2. the time to clinical cure (for symptomatic patients)
3. the proportion of patients with virological clearance at day 14 and 30.
4. the hospitalization rate.
5. the COVID-19 Severity Score at day 14 and 30

STUDY DESIGN

This is a multicentre, prospective, randomized, double-blind, adaptive phase II dose finding study.

Patients meeting the inclusion criteria will be asked to participate to the study and randomized in a 1:1:1 ratio to either:

• Placebo arm (arm A): placebo will be identical in appearance to ivermectin in order to preserve blinding and will be administered p.o. at empty stomach with water once daily, for 5 days

• Intervention arms:

  • Arm B: vermectin, single dose 600 μg/kg, for 5 days (I_600) and placebo;
  • Arrn C: Ivermectin, single dose 1200 μg/kg, for 5 days (I_1200) (arm C) ); these drugs will be administered p.o. once daily, for 5 days.

In arm A and B, the number of placebo tablets to be administered will be calculated by the study dedicated pharmacist considering the number of tablets that should be taken in case a patient with the same weight is assigned to arm C.

Patients will be randomized by a centralized computer system. At randomization a treatment ID is assigned to the patient. Once a treatment ID is assigned this must not be re-assigned even in cases of errors.

Enrolled subjects will be identified by a unique subject number (patient code) that will remain consistent for the duration of the study.

Patients will be recruited at the emergency room of hospitals, and/or among asymptomatic hospital workers found positive for SARS-CoV-2 at routine screening and/or in outpatient ambulatory settings, and/or at home, if not meeting the clinical criteria for hospitalization, according to the routine procedure of each participating site. The expected duration of subject inclusion in the study is of 1 month, or until the planned number of subjects to be enrolled will be reached.

N=102, random assignment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: Ivermectin and placebo treatment will be double blinded, i.e. the treatment will be unknown to both the subject and the treating physician. The hospital pharmacist will be unblinded to study treatment because in charge to prepare the study treatment according to randomization arm.

Primary completion date: August 2020 Study completion date: October 2020

Primary outcomes:

1. SADR [Time frame 14 days] - Number of serious adverse drug reaction
2. Viral load [Time frame: Assessed at day 7] - Quantitative viral load as measured by quantitative, digital droplet PCR.

[There are 6 secondary outcomes -- see the entry on ClinicalTrials]

Subjects: 18+, positive PCR test, severity score < 3, who are not being treated with warfarin, other antivirals, chloroquine phosphate or hydroxychloroquine

Thoughts:

This is great! A recently-added study was IMO a complete waste, testing 1 or 2 doses of ivermectin at 100mcg/kg or 200mcg/kg - when there are LOTS of studies at 200mcg/kg, and there is no reason to test lower levels of the drug. THIS study is testing the largest doses to date, by a large margin. The protocol description is ambiguous, esp. the "Intervention/treatment" language is identical for both experimental arms. From the Arm column and the description, the doses are:

• 600mcg/kg * 5 days

This exceeds every other trial; the second highest dose is the Israel study administering 600mcg/kg for only 3 days, not 5.

• 1200mcg/kg * 5 days (regardless of their weight)

This adds up to 6000mcg/kg -- literally 10 times the Israel trial dose!

At 3000mcg/kg and 6000mcg/kg, both arms exceed the limit evaluated by Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects, which found that 2000mcg/kg did not present CNS (Central Nervous System) symptoms.

It will be exciting to see what happens!

This is a well-designed study: multi-center, RCT with great masking. The N=102 means there will be 34 in each of the two experimental arms, which is probably enough (depends on the size of the ivermectin effect). The outcome measurements are fine.

Not that I'm God's gift to anything -- but I have nothing to criticize! :)

Also posted to /r/covid19.

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This “trial” is designed to force side effects to disparage its use , they are using patients with a compromised blood brain barrier. There might even be deaths.

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