A Study to Compare the Efficacy and Safety of Different Doses of Ivermectin for COVID-19 (IFORS)

Phase 2 Clinical Trial to Compare the Efficacy and Safety of Different Doses of Ivermectin in Patients Diagnosed With the New Coronavirus Infection (SARS-CoV-2)

In December 2019, a group of patients with pneumonia of unknown cause was linked to a wholesale seafood market in Wuhan, China. The genetic analysis of samples from the lower respiratory tract of these patients indicated a new coronavirus as the causative agent, which was named SARS-CoV-2. The virus spread rapidly to more than 45 countries, including Brazil, causing an international alarm. However, in spite of its epidemiological magnitude, so far, there is no antiviral treatment or vaccine approved for the treatment of this infection. With about 15% to 20% of SARS-CoV-2 patients suffering from serious illnesses and overburdened hospitals, therapeutic options are desperately needed. So, instead of creating compounds from scratch that can take years to develop and test, researchers and public health agencies have sought to redirect drugs already approved for other diseases and known to be widely safe. In this context, the analysis of the international literature shows the existence of an in vitro antiviral activity of ivermectin against SARS-CoV-2. However, there are no studies that have evaluated its clinical effectiveness in patients diagnosed with SARS-CoV-2 infection. Therefore, and considering this knowledge gap, the present study aims to determine the clinical efficacy and safety of different doses of ivermectin in patients diagnosed with SARS-CoV-2 infection.

Study Overview

• Status: Terminated
• Conditions: Coronavirus Infection
• Intervention / Treatment: Other: Standard of Care; Drug: Ivermectin

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • São Carlos, São Paulo, Brazil, 13565-905
      • Hospital Univeristário da Universidade Federal de São Carlos (HU-UFSCar)
    • São Carlos, São Paulo, Brazil, 13566-448
      • Hospital Universitário da Universidade Federal de São Carlos (HU-UFSCar)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of infection by SARS-CoV-2:

  1. symptoms of acute respiratory tract infection (sudden onset of at least one of the following: cough, fever, shortness of breath) and biomolecular diagnosis of SARS-CoV-2 infection; OR
  2. any acute respiratory disease AND biomolecular diagnosis of SARS-CoV-2 infection; OR
  3. severe acute respiratory infection (fever and at least one sign / symptom of respiratory disease eg cough, fever, shortness of breath) AND in need of hospitalization AND biomolecular diagnosis of SARS-CoV-2 infection;
• Eastern Cooperative Oncology Group Performance Status score 0 to 1;
• National Early Warning Score 0 to 4;
• Ability to understand and consent to participate in this clinical trial, manifested by signing the Informed Consent Form (ICF).

Exclusion Criteria:

• Inability to ingest / absorb the study drug orally through spontaneous ingestion or use of gastro / enteral tubes;
• Any finding of clinical observation (history / physical evaluation) that is interpreted by the investigating physician as a risk to participate in the trial;
• Any laboratory test findings that the investigating physician considers as a risk to the research participant as to his / her participation in the clinical study;
• Any ECG examination finding that the investigating physician considers as a risk to the research participant as to his / her participation in the trial;
• Known hypersensitivity to the components of the drugs used during the study;
• Women in pregnancy or breastfeeding;
• Body weight less than 15kg;
• Estimated glomerular filtration rate (CKD-Epidemiology Collaboration, CKD-EPI) <30 mL / min;
• Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT)> 5 times the upper limit of normality;
• Refusal to participate;
• Refusal to sign the informed consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of care; Standard of care (SOC) treatment	Other: Standard of Care; Standard treatment for COVID-19
Experimental: SOC plus ivermectin 100 mcg/kg	Drug: Ivermectin; SOC plus different dosing regimens of Ivermectin
Experimental: SOC plus ivermectin 200 mcg/kg	Drug: Ivermectin; SOC plus different dosing regimens of Ivermectin
Experimental: SOC plus ivermectin 400 mcg/kg	Drug: Ivermectin; SOC plus different dosing regimens of Ivermectin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Undetectable viral load during 7 days of follow-up.	Proportion of patients who achieved undetectable viral load during 7 days of follow-up.	7 days following intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral load variation in the nasopharyngeal swab.	Viral load variation in the nasopharyngeal swab during treatment.	7 days following intervention.
Time to undetectable SARS-CoV-2 viral load in the nasopharyngeal swab.	Variation of serum lymphocyte counts during treatment.	7 days following intervention.
Incidence of Treatment-Emergent Self-reported Adverse Events	Incidence of Treatment-Emergent Adverse Events as assessed by clinical history and physical examination	28 days following intervention.
Incidence of Treatment-Emergent Laboratory-based Adverse Events	Incidence of Treatment-Emergent Adverse Events as assessed by laboratory tests	28 days following intervention.

Collaborators and Investigators

• Sponsor: Universidade Federal de Sao Carlos
• Investigators: Principal Investigator: Henrique Pott Junior, MD PhD, Universidade Federal de Sao Carlos

Publications and helpful links

General Publications

• Pott-Junior H, Paoliello MMB, Miguel AQC, da Cunha AF, de Melo Freire CC, Neves FF, da Silva de Avo LR, Roscani MG, Dos Santos SS, Chacha SGF. Use of ivermectin in the treatment of Covid-19: A pilot trial. Toxicol Rep. 2021;8:505-510. doi: 10.1016/j.toxrep.2021.03.003. Epub 2021 Mar 9.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; clinical trial; ivermectin; coronavirus infections
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Coronavirus Infections; Infections; Anti-Infective Agents; Antiparasitic Agents; Ivermectin
• Other Study ID Numbers: IFORS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No