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

Phase 2

Completed

• Conditions: Covid-19; Coronavirus Infection; SARS-CoV-2 Infection
• Interventions: Drug: Placebo; Drug: Ivermectin

• Registration Number: NCT04390022
• Lead Sponsor: Clinica Universidad de Navarra, Universidad de Navarra

Brief Summary

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

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A final study visit will be made for participants who withdraw prematurely from the study or are withdrawn by the investigator.

Study Timeline

• Study First Submitted: 2020-05-07
• Study First Submitted QC: 2020-05-14
• Study First Posted: 2020-05-15
• Study Start: 2020-07-31
• Primary Completion: 2020-09-17
• Study Completion: 2020-10-09
• Status Verified: 2020-12
• Results First Submitted: 2020-12-09
• Results First Submitted QC: 2020-12-10
• Last Update Submitted: 2020-12-10
• Results First Posted: 2020-12-17
• Last Update Posted: 2020-12-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Patients diagnosed with COVID-19 in the emergency room of the Clínica Universidad de Navarra with a positive SARS-CoV-2 PCR.

2. Residents of the Pamplona basin ("Cuenca de Pamplona")

3. The patient should be aged 18 to 59 years

4. Negative pregnancy test for women of child bearing age*

5. The patient or his/her representative, have given consent to participate in the study.

6. 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)

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Exclusion Criteria

1. Known history of Ivermectin allergy

2. Hypersensitivity to any component of Stromectol®

3. COVID-19 Pneumonia

   • Diagnosed by the attending physician
   • Identified in a chest X-ray

4. Fever or cough present for more than 48 hours

5. Positive IgG against SARS-CoV-2 by rapid test

6. Age under 18 or over 60 years

7. 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

8. 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)

9. 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants on the arm will receive a single, oral dose of placebo tablets at the enrollment visit.
Ivermectin	Ivermectin	Participants on this arm will receive a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit.

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With a Positive SARS-CoV-2 PCR	7 days post-treatment	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).

Secondary Outcome Measures

Name	Time	Method
Results From Cytokine Human Magnetic 30-Plex Panel	Up to and including day 28	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).; \[Results not yet available\]
Seroconversion at Day 21	Up to and including day 21	Proportion of participants with positive IgG at day 21
Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T Cells	Up to and including day 7	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.; \[Results not yet available\]
Fever and Cough Progression	Days 4, 7, 14 and 21	Proportion of patients with fever and cough
Median Viral Load	Baseline and on days 4, 7, 14 and 21	Quantitative and semi-quantitative PCR in nasopharyngeal swab. PCRs were performed using two target genes (E and N).
Frequency of Innate Immune Cells	Up to and including day 7	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.; \[Results not yet available\]
Proportion of Drug-related Adverse Events	7 days post treatment	Proportion of drug-related adverse events
Levels of IgG, IgM and IgA	Up to and including day 28	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.; \[Results not yet available\]

Trial Locations

Locations (1)

Clinica Universidad de Navarra; 🇪🇸 Pamplona, Navarra, Spain