Ivermectin in Adults With Severe COVID-19.

Sponsor

CES University (Other)

Overall Status

Terminated

CT.gov ID

NCT04602507

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

6.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Since the onset of the disease, more than 40.5 million people have been diagnosed with COVID-19 and nearly 1.2 million people have died (October 21, 2020). There is no complete understanding of the pathogenesis of SARS-CoV-2 infection and to this day there is no specific therapy or vaccine available. Thus, patient care is based on symptomatic therapy and treatment of complications.

Ivermectin has been used for more than 30 years for the treatment of several diseases. More than one million doses of the drug are administered daily, particularly in low- and middle-income countries. Due to the low prevalence of adverse events with the use of this drug, ivermectin is considered to have a good safety profile and its potential benefit in other diseases is currently under investigation.

An in vitro study of ivermectin in SARS-CoV-2 in Australia showed a significant reduction of viral load in infected cells. Subsequently, a descriptive study of 704 critical patients with COVID-19 showed a reduction in mortality, hospitalization, and intensive care unit length-of-stay in those patients who received the drug. Unfortunately, this study was withdrawn by its authors, leaving more questions than answers.

Some countries in Latin America have authorized its use for the management of patients with COVID-19 even in the absence of solid evidence, and several other countries are conducting clinical trials to evaluate its efficacy for the treatment of moderate and severe disease.

Since there is no specific treatment for COVID-19 and the therapeutic options are scarce, the researchers believe it is completely plausible, urgent, and necessary to evaluate if ivermectin use reduces the risk of admission to an intensive care unit (ICU) in hospitalized adults with severe COVID-19. The proposal is a randomized, double-blind clinical trial, conducted at CES Clinic, Medellin-Colombia. The investigators will randomize 100 patients with severe, non-critical illness, into two groups, one group will receive ivermectin in addition to standard management and the other group will receive placebo plus standard management. Clinical outcomes to evaluate will be ICU admission, need for mechanical ventilation, length of hospital stay, days in the ICU and mechanical ventilation, and finally, the incidence of adverse events related to the intervention. The estimated time to complete the study is approximately five months.

Condition or Disease	Intervention/Treatment	Phase
Covid19 Severe Acute Respiratory Syndrome	Drug: Ivermectin Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Arm #1: 50 patients with routine care offered in the hospital plus ivermectin 400 µg/kg orally in a single dose. Arm #2: 50 patients with routine care offered in the hospital plus placebo in a single dose.Arm #1: 50 patients with routine care offered in the hospital plus ivermectin 400 µg/kg orally in a single dose. Arm #2: 50 patients with routine care offered in the hospital plus placebo in a single dose.

Masking:

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

Masking Description:

Once the participant consents, staff will collect relevant demographic and clinical data from the clinical chart and a consecutive code from 001 to 100 will be assigned to each in order of arrival. 100 vials of ivermectin or placebo will be stored in the pharmaceutical service with a randomly assigned number from 001 to 100. After placement of medical order, the qualified nursing staff will dispense ivermectin or placebo. Blinded study physicians will carry on daily medical evaluation. Neither the researchers collecting data nor the analyzers will be aware of the patients' treatment arm. To achieve blinding, a certified pharmaceutical laboratory produced a placebo identical in color, physical form, sensory perception (appearance, smell, and taste), packaging, and labeling to ivermectin.

Primary Purpose:

Treatment

Official Title:

Ivermectin in Adults With Severe COVID-19. Double-blind Randomized Clinical Trial

Actual Study Start Date :

Dec 10, 2020

Actual Primary Completion Date :

Dec 9, 2021

Actual Study Completion Date :

Dec 9, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention 50 patients with the routine care offered in the hospital plus ivermectin 400 µg/kg (2 drops per kg) orally in a single dose.	Drug: Ivermectin Routinary care offered in the hospital plus ivermectin 400 µg/kg (2 drops per kg) orally in a single dose. Other Names: Intervention
Placebo Comparator: Control 50 patients with routine care offered in the hospital plus placebo orally (2 drops per kg) in a single dose.	Other: Placebo Routinary care offered in the hospital plus placebo (2 drops per kg) orally in a single dose Other Names: Control

Arm

Intervention/Treatment

Experimental: Intervention

50 patients with the routine care offered in the hospital plus ivermectin 400 µg/kg (2 drops per kg) orally in a single dose.

Drug: Ivermectin

Routinary care offered in the hospital plus ivermectin 400 µg/kg (2 drops per kg) orally in a single dose.

Other Names:

Intervention

Placebo Comparator: Control

50 patients with routine care offered in the hospital plus placebo orally (2 drops per kg) in a single dose.

Other: Placebo

Routinary care offered in the hospital plus placebo (2 drops per kg) orally in a single dose

Other Names:

Control

Outcome Measures

Primary Outcome Measures

Admission to the intensive care unit. [21 days]
Cumulative incidence of ICU admission.

Secondary Outcome Measures

Hospital length of stay. [21 days]
Duration of hospitalization (days).
Mortality rate. [21 days]
21-day mortality.
ICU length of stay. [21 days]
Number of days in ICU.
Length of stay in ventilator time. [21 days]
Number of days with mechanical ventilator.
Adverse effects of ivermectin. [21 days]
Cumulative incidence of adverse effects: headache, rash, pruritus, arthralgia, tachycardia, dizziness, hypotension, uveitis, Steven Johnson Syndrome.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Over 18 years old.
Confirmed diagnosis of SARS-CoV-2 by polymerase chain reaction (PCR).
Diagnosis of severe pneumonia according to criteria of the National Institute of Health and the Colombian Consensus (suspected respiratory infection, organ failure, arterial oxygen saturation (SaO2) ambient air <90% or respiratory rate > 30 resp/min) or diagnosis of acute respiratory distress syndrome according to criteria of the National Institute of Health and the Colombian Consensus (clinical findings, bilateral radiographic infiltrates, + oxygenation deficit as well: mild: 200 mmHg < PaO2/FiO2 (fraction of inspired oxygen) < 300 mm/Hg; moderate: 100 mm/Hg < PaO2/FiO2 < 200 mm/Hg and, severe: PaO2/FiO2 < 100 mm/Hg).
Less than 14 days since the onset of symptoms.
Hospitalized in a general internal medicine ward, special care unit, or those designated for managing patients with COVID19.

Exclusion Criteria:

Pregnant or lactating women.
Use of ivermectin in the two weeks before admission to the clinic
Diseases affecting the blood-brain barrier (meningitis, encephalocranial trauma, acute subarachnoid hemorrhage)
Limitation to understanding the explanations and giving consent, defined by the investigating physician.
Patients with HIV/AIDS
That the patient is participating in another clinical trial.