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

• ClinicalTrials.gov Identifier: NCT04431466
• Recruitment Status: Recruiting
• First Posted: June 16, 2020
• Last Update Posted: September 2, 2020
• Sponsor: Universidade Federal de Sao Carlos
• Information provided by (Responsible Party): Henrique Pott Junior, Universidade Federal de Sao Carlos

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Coronavirus Infection	Drug: Ivermectin; Other: Standard treatment for COVID-19	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: July 1, 2020
• Estimated Primary Completion Date: December 1, 2020
• Estimated Study Completion Date: July 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard treatment; Standard treatment for COVID-19	Other: Standard treatment for COVID-19; Standard treatment for COVID-19
Experimental: Ivermectin lower single-dose; Ivermectin 100mcg / kg PO single dose	Drug: Ivermectin; This clinical trial will evaluate the efficacy between different ivermectin dosing schedules (100mcg / kg PO single dose; 100mcg / kg PO on the first day, followed by 100mcg / kg PO after 72h; 200mcg / kg PO single dose; and 200mcg / kg on the first day, followed by 200mcg / kg PO after) for the treatment of individuals with diagnosis SARS-CoV-2 infection.
Experimental: Ivermectin lower repeated-dose; 100mcg / kg PO on the first day, followed by 100mcg / kg PO after 72h	Drug: Ivermectin; This clinical trial will evaluate the efficacy between different ivermectin dosing schedules (100mcg / kg PO single dose; 100mcg / kg PO on the first day, followed by 100mcg / kg PO after 72h; 200mcg / kg PO single dose; and 200mcg / kg on the first day, followed by 200mcg / kg PO after) for the treatment of individuals with diagnosis SARS-CoV-2 infection.
Experimental: Ivermectin higher single-dose; Ivermectin 200mcg / kg PO single dose	Drug: Ivermectin; This clinical trial will evaluate the efficacy between different ivermectin dosing schedules (100mcg / kg PO single dose; 100mcg / kg PO on the first day, followed by 100mcg / kg PO after 72h; 200mcg / kg PO single dose; and 200mcg / kg on the first day, followed by 200mcg / kg PO after) for the treatment of individuals with diagnosis SARS-CoV-2 infection.
Experimental: Ivermectin higher repeated-dose; 200mcg / kg PO on the first day, followed by 200mcg / kg PO after 72h	Drug: Ivermectin; This clinical trial will evaluate the efficacy between different ivermectin dosing schedules (100mcg / kg PO single dose; 100mcg / kg PO on the first day, followed by 100mcg / kg PO after 72h; 200mcg / kg PO single dose; and 200mcg / kg on the first day, followed by 200mcg / kg PO after) for the treatment of individuals with diagnosis SARS-CoV-2 infection.

Outcome Measures

Primary Outcome Measures :

1. Time to undetectable SARS-CoV-2 viral load in the nasopharyngeal swab. [ Time Frame: 7 days following intervention ]
   Time to undetectable SARS-CoV-2 viral load in the nasopharyngeal swab after Intervention Initiation.

Secondary Outcome Measures :

1. Viral load variation in the nasopharyngeal swab. [ Time Frame: 7 days following intervention. ]
   Viral load variation in the nasopharyngeal swab during treatment.
2. Time to undetectable SARS-CoV-2 viral load in the nasopharyngeal swab. [ Time Frame: 7 days following intervention. ]
   Variation of serum lymphocyte counts during treatment.
3. Proportion of patients with undetectable SARS-CoV-2 viral load in the nasopharyngeal swab. [ Time Frame: 7 after intervention. ]
   Proportion of patients with undetectable SARS-CoV-2 viral load in the nasopharyngeal swab at the end of follow-up.
4. Proportion of patients with clinical improvement. [ Time Frame: 7 after intervention. ]
   Proportion of patients with clinical improvement, defined as the time to normalize fever, respiratory rate and oxygen saturation and cough relief at the end of follow-up.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Henrique Pott Junior, MD PhD; +55 16 3351-8340; henriquepott@ufscar.br

Locations

Brazil

Hospital Univeristário da Universidade Federal de São Carlos (HU-UFSCar); Not yet recruiting

São Carlos, São Paulo, Brazil, 13565-905

Contact: Henrique Pott Junior, MD PhD henriquepott@ufscar.br

Hospital Universitário da Universidade Federal de São Carlos (HU-UFSCar); Recruiting

São Carlos, São Paulo, Brazil, 13566-448

Contact: Henrique Pott Junior, MD PhD henriquepott@ufscar.br

Principal Investigator: Henrique Pott Junior, MD PhD

Sponsors and Collaborators

Universidade Federal de Sao Carlos

Investigators

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

More Information

Additional Information:

Hospital Universit&#225;rio da UFSCar 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pott-Junior H, Bastos Paoliello MM, Miguel AQC, da Cunha AF, de Melo Freire CC, Neves FF, da Silva de Avó LR, Roscani MG, Dos Santos SS, Chachá 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.

• Responsible Party: Henrique Pott Junior, Professor, Universidade Federal de Sao Carlos
• ClinicalTrials.gov Identifier: NCT04431466
• Other Study ID Numbers: IFORS
• First Posted: June 16, 2020
• Last Update Posted: September 2, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Henrique Pott Junior, Universidade Federal de Sao Carlos:

coronavirus infections; SARS-CoV-2; COVID-19; ivermectin; clinical trial

Additional relevant MeSH terms:

Infection; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Ivermectin; Antiparasitic Agents; Anti-Infective Agents