Sars-CoV-2/COVID-19 Ivermectin Navarra-ISGlobal Trial

Study Overview
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Brief Summary
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SAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease. The trial is currently planned at a single center in Navarra.

Detailed Description
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SAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease. The trial is currently planned at a single center in Navarra. Participants will be randomized to receive a single dose of 400 mcg/kg ivermectin or a placebo. The randomization code will be generated by the trial statistician using blocks that ensure balance between the groups. The allocation will be made by the investigator after obtaining informed consent, and confirmation of fulfillment of all inclusion and none of the exclusion criteria. The investigational product will be administered by a researcher not involved in patient care or participant follow up. Participants will remain in the trial for a period of 28 days. In the interests of public health and containing transmission of infection, trial visits will be conducted in the participant's home by a clinical trial team comprising nursing and medical members. Subsequent visits will be to assess clinical and laboratory parameters. A final study visit will be made for participants who withdraw prematurely from the study or are withdrawn by the investigator.

Official Title
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Pilot Study to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission

Conditions
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Covid-19, Coronavirus Infection, SARS-CoV-2 Infection

Intervention / Treatment
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* Drug: Ivermectin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with COVID-19 in the emergency room of the Clínica Universidad de Navarra with a positive SARS-CoV-2 PCR. Residents of the Pamplona basin (Cuenca de Pamplona) The patient should be aged 18 to 59 years Negative pregnancy test for women of child bearing age* The patient or his/her representative, have given consent to participate in the study. The patient should, in the investigator's opinion, be able to comply with all the requirements of the clinical trial (including home follow up during isolation) Women of child bearing age may participate if they use a safe contraceptive method for the entire period of the study and at least one month afterwards. A woman is considered to not have childbearing capacity if she is post-menopausal (minimum of 2 years without menstruation) or has undergone surgical sterilization (at least one month before the study) Exclusion Criteria: Known history of Ivermectin allergy Hypersensitivity to any component of Stromectol® COVID-19 Pneumonia Diagnosed by the attending physician Identified in a chest X-ray Fever or cough present for more than 48 hours Positive IgG against SARS-CoV-2 by rapid test Age under 18 or over 60 years The following co-morbidities (or any other disease that might interfere with the study in the eyes of the investigator): Immunosuppression Chronic Obstructive Pulmonary Disease Diabetes Hypertension Obesity Acute or chronic renal failure History of coronary disease History of cerebrovascular disease Current neoplasm Recent travel history to countries that are endemic for Loa loa (Angola, Cameroon, Central African Republic, Chad, Democratic Republic of Congo, Ethiopia, Equatorial, Guinea, Gabon, Republic of Congo, Nigeria and Sudan) Current use of CYP 3A4 or P-gp inhibitor drugs such as quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir or cobicistat. Use of critical CYP3A4 substrate drugs such as warfarin.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: SAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ivermectin<br>Participants on this arm will receive a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit. | Drug: Ivermectin<br>* Single dose of STROMECTOL® tablets at 400mcg/kg<br>* Other names: Stromectol;|
| Placebo Comparator: Placebo<br>Participants on the arm will receive a single, oral dose of placebo tablets at the enrollment visit. | Drug: Placebo<br>* Placebo tablets will not match ivermectin but they will be administered by staff not involved in the clinical care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With a Positive SARS-CoV-2 PCR | Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. PCRs were performed using two target genes (E and N). | 7 days post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Viral Load | Quantitative and semi-quantitative PCR in nasopharyngeal swab. PCRs were performed using two target genes (E and N). | Baseline and on days 4, 7, 14 and 21 | 
| Fever and Cough Progression | Proportion of patients with fever and cough | Days 4, 7, 14 and 21 | 
| Seroconversion at Day 21 | Proportion of participants with positive IgG at day 21 | Up to and including day 21 | 
| Proportion of Drug-related Adverse Events | Proportion of drug-related adverse events | 7 days post treatment | 
| Levels of IgG, IgM and IgA | Levels in median fluorescence intensity (MFI) of IgG, IgM and IgA against the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 in plasma, measured by a Luminex assay. [Results not yet available] | Up to and including day 28 | 
| Frequency of Innate Immune Cells | Frequency (% over total PBMC) of innate immune cells (myeloid and plasmacytoid dendritic cells, NK cell, classical, intermediate and pro-inflammatory macrophages) measured in cryopreserved PBMC by flow cytometry. [Results not yet available] | Up to and including day 7 | 
| Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T Cells | Frequency of CD4+ T and CD8+ T cells (% over total CD4+T and CD8+ T) expressing any functional marker upon in vitro stimulation of PBMC with SARS-CoV-2 peptides, measured by flow cytometry. [Results not yet available] | Up to and including day 7 | 
| Results From Cytokine Human Magnetic 30-Plex Panel | Concentration (all in pg/mL) of epidermal growth factor (EGF), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1RA, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p40/p70), IL-13, IL-15, IL-17, IFN-γ induced protein (IP-10), monocyte chemoattractant protein (MCP-1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein (MIP)-1α, MIP-1β in plasma measured by a Luminex assay using a commercially available kit (Cytokine Human Magnetic 30-Plex Panel from ThermoFisher). [Results not yet available] | Up to and including day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ivermectin