Sars-CoV-2/COVID-19 Ivermectin Navarra-ISGlobal Trial (SAINT)

• ClinicalTrials.gov Identifier: NCT04390022
• Recruitment Status: Completed
• First Posted: May 15, 2020
• Results First Posted: December 17, 2020
• Last Update Posted: December 17, 2020
• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Collaborator: Barcelona Institute for Global Health
• Information provided by (Responsible Party): Clinica Universidad de Navarra, Universidad de Navarra

Tracking Information

• First Submitted Date: May 7, 2020
• First Posted Date: May 15, 2020
• Results First Submitted Date: December 9, 2020
• Results First Posted Date: December 17, 2020
• Last Update Posted Date: December 17, 2020
• Actual Study Start Date: July 31, 2020
• Actual Primary Completion Date: September 17, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 10, 2020)

Proportion of Patients With a Positive SARS-CoV-2 PCR [ Time Frame: 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).

Original Primary Outcome Measures (submitted: May 14, 2020)

Proportion of Patients With a Positive SARS-CoV-2 PCR [ Time Frame: 7 days post-treatment ]

Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment

Current Secondary Outcome Measures (submitted: December 10, 2020)

• Median Viral Load [ Time Frame: 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).
• Fever and Cough Progression [ Time Frame: Days 4, 7, 14 and 21 ]
  Proportion of patients with fever and cough
• Seroconversion at Day 21 [ Time Frame: Up to and including day 21 ]
  Proportion of participants with positive IgG at day 21
• Proportion of Drug-related Adverse Events [ Time Frame: 7 days post treatment ]
  Proportion of drug-related adverse events
• Levels of IgG, IgM and IgA [ Time Frame: 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]
• Frequency of Innate Immune Cells [ Time Frame: 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]
• Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T Cells [ Time Frame: 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]
• Results From Cytokine Human Magnetic 30-Plex Panel [ Time Frame: 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]

Original Secondary Outcome Measures (submitted: May 14, 2020)

• Mean viral load [ Time Frame: Baseline and on days 4, 7, 14 and 21 ]
  Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab
• Fever and Cough Progression [ Time Frame: Up to and including day 21 ]
  Proportion of patients with fever and cough at days 4, 7, 14 and 21 as well as proportion of patients progressing to severe disease or death during the trial
• Seroconversion at Day 21 [ Time Frame: Up to and including day 21 ]
  Proportion of participants with positive IgG at day 21
• Proportion of Drug-related Adverse Events [ Time Frame: 7 days post treatment ]
  Proportion of drug-related adverse events
• Levels of IgG, IgM and IgA [ Time Frame: 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
• Frequency of Innate Immune Cells [ Time Frame: 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
• Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T Cells [ Time Frame: 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 From Cytokine Human Magnetic 30-Plex Panel [ Time Frame: 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)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sars-CoV-2/COVID-19 Ivermectin Navarra-ISGlobal Trial
• Official Title: Pilot Study to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission
• 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 Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Investigator)
Masking Description:

Double blind

Primary Purpose: Treatment

Condition

• Covid-19
• Coronavirus Infection
• SARS-CoV-2 Infection

Intervention

• Drug: Ivermectin
  Single dose of STROMECTOL® tablets at 400mcg/kg
  Other Name: Stromectol
• Drug: Placebo
  Placebo tablets will not match ivermectin but they will be administered by staff not involved in the clinical care.

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 14, 2020): 24
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 9, 2020
• Actual Primary Completion Date: September 17, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 59 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT04390022
• Other Study ID Numbers: SAINT
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
• Study Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Collaborators: Barcelona Institute for Global Health

Investigators

• Principal Investigator: Carlos J Chaccour, MD PhD; Clinica Universidad de Navarra and Barcelona Institute of Global Health

• PRS Account: Clinica Universidad de Navarra, Universidad de Navarra
• Verification Date: December 2020