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

Sponsor
Clinica Universidad de Navarra, Universidad de Navarra (Other)
Overall Status
Completed
CT.gov ID
NCT04390022
Collaborator
Barcelona Institute for Global Health (Other)
24
1
2
2.3
10.4

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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A final study visit will be made for participants who withdraw prematurely from the study or are withdrawn by the investigator.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

Study Type:
Interventional
Actual Enrollment :
24 participants
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.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
Official Title:
Pilot Study to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission
Actual Study Start Date :
Jul 31, 2020
Actual Primary Completion Date :
Sep 17, 2020
Actual Study Completion Date :
Oct 9, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Ivermectin

Participants on this arm will receive a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit.

Drug: Ivermectin
Single dose of STROMECTOL® tablets at 400mcg/kg
Other Names:
  • Stromectol
  • Placebo Comparator: Placebo

    Participants on the arm will receive a single, oral dose of placebo tablets at the enrollment visit.

    Drug: Placebo
    Placebo tablets will not match ivermectin but they will be administered by staff not involved in the clinical care.

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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).

    2. Fever and Cough Progression [Days 4, 7, 14 and 21]

      Proportion of patients with fever and cough

    3. Seroconversion at Day 21 [Up to and including day 21]

      Proportion of participants with positive IgG at day 21

    4. Proportion of Drug-related Adverse Events [7 days post treatment]

      Proportion of drug-related adverse events

    5. 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]

    6. 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]

    7. 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]

    8. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 59 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. Fever or cough present for more than 48 hours

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

    3. Age under 18 or over 60 years

    4. 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

    1. 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)

    2. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinica Universidad de Navarra Pamplona Navarra Spain 31108

    Sponsors and Collaborators

    • Clinica Universidad de Navarra, Universidad de Navarra
    • Barcelona Institute for Global Health

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Clinica Universidad de Navarra, Universidad de Navarra
    ClinicalTrials.gov Identifier:
    NCT04390022
    Other Study ID Numbers:
    • SAINT
    First Posted:
    May 15, 2020
    Last Update Posted:
    Dec 17, 2020
    Last Verified:
    Dec 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Clinica Universidad de Navarra, Universidad de Navarra
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ivermectin Placebo
    Arm/Group Description Participants on this arm received a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit. (Single dose of STROMECTOL® tablets at 400mcg/kg) Participants on this arm received a single, oral dose of placebo tablets at the enrollment visit. (Placebo tablets did not match ivermectin but they were administered by staff not involved in the clinical care)
    Period Title: Overall Study
    STARTED 12 12
    COMPLETED 12 12
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Ivermectin Placebo Total
    Arm/Group Description Participants on this arm received a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit. (Single dose of STROMECTOL® tablets at 400mcg/kg) Participants on this arm received a single, oral dose of placebo tablets at the enrollment visit. (Placebo tablets did not match ivermectin but they were administered by staff not involved in the clinical care) Total of all reporting groups
    Overall Participants 12 12 24
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    26
    26
    26
    Sex: Female, Male (Count of Participants)
    Female
    5
    41.7%
    7
    58.3%
    12
    50%
    Male
    7
    58.3%
    5
    41.7%
    12
    50%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Body mass index (kg/m^2) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [kg/m^2]
    23.5
    22.9
    22.9
    Any symptoms (Count of Participants)
    Count of Participants [Participants]
    12
    100%
    12
    100%
    24
    100%
    Earliest start of any symptom (hours) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [hours]
    24
    48
    48
    Fever (Count of Participants)
    Count of Participants [Participants]
    7
    58.3%
    9
    75%
    16
    66.7%
    Earliest start of fever (hours) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [hours]
    24
    24
    24
    Cough (Count of Participants)
    Count of Participants [Participants]
    4
    33.3%
    2
    16.7%
    6
    25%
    Earliest start of cough (hours) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [hours]
    24
    10
    18
    CRP (mg/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL]
    0.3
    0.3
    0.3
    Ferritin (mg/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL]
    165.0
    156.1
    160.9
    IL-6 (pg/mL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [pg/mL]
    6.5
    4.5
    5.3
    D-Dimer (ng/mL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ng/mL]
    295
    280
    285

    Outcome Measures

    1. Primary Outcome
    Title Proportion of Patients With a Positive SARS-CoV-2 PCR
    Description 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).
    Time Frame 7 days post-treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ivermectin Placebo
    Arm/Group Description Participants on this arm received a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit. (Single dose of STROMECTOL® tablets at 400mcg/kg) Participants on this arm received a single, oral dose of placebo tablets at the enrollment visit. (Placebo tablets did not match ivermectin but they were administered by staff not involved in the clinical care)
    Measure Participants 12 12
    PCR positivity (gene N)
    12
    100%
    12
    100%
    PCR positivity (gene E)
    11
    91.7%
    12
    100%
    2. Secondary Outcome
    Title Median Viral Load
    Description Quantitative and semi-quantitative PCR in nasopharyngeal swab. PCRs were performed using two target genes (E and N).
    Time Frame Baseline and on days 4, 7, 14 and 21

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ivermectin Placebo
    Arm/Group Description Participants on this arm received a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit. (Single dose of STROMECTOL® tablets at 400mcg/kg) Participants on this arm received a single, oral dose of placebo tablets at the enrollment visit. (Placebo tablets did not match ivermectin but they were administered by staff not involved in the clinical care)
    Measure Participants 12 12
    Gene E - day 1
    16850000
    26700000
    Gene E - day 4
    161000
    493500
    Gene E - day 7
    1018
    23550
    Gene E - day 14
    7
    30
    Gene E - day 21
    1
    0
    Gene N - day 1
    367000000
    327500000
    Gene N - day 4
    269000
    2194500
    Gene N - day 7
    2255
    36800
    Gene N - day 14
    86
    75
    Gene N - day 21
    0
    107
    3. Secondary Outcome
    Title Fever and Cough Progression
    Description Proportion of patients with fever and cough
    Time Frame Days 4, 7, 14 and 21

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ivermectin Placebo
    Arm/Group Description Participants on this arm received a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit. (Single dose of STROMECTOL® tablets at 400mcg/kg) Participants on this arm received a single, oral dose of placebo tablets at the enrollment visit. (Placebo tablets did not match ivermectin but they were administered by staff not involved in the clinical care)
    Measure Participants 12 12
    Fever - Day 4
    0
    0%
    0
    0%
    Fever - Day 7
    1
    8.3%
    0
    0%
    Fever - Day 14
    0
    0%
    0
    0%
    Fever - Day 21
    0
    0%
    0
    0%
    Cough - Day 4
    5
    41.7%
    6
    50%
    Cough - Day 7
    5
    41.7%
    5
    41.7%
    Cough - Day 14
    1
    8.3%
    3
    25%
    Cough - Day 21
    1
    8.3%
    3
    25%
    4. Secondary Outcome
    Title Seroconversion at Day 21
    Description Proportion of participants with positive IgG at day 21
    Time Frame Up to and including day 21

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ivermectin Placebo
    Arm/Group Description Participants on this arm received a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit. (Single dose of STROMECTOL® tablets at 400mcg/kg) Participants on this arm received a single, oral dose of placebo tablets at the enrollment visit. (Placebo tablets did not match ivermectin but they were administered by staff not involved in the clinical care)
    Measure Participants 12 12
    Count of Participants [Participants]
    12
    100%
    12
    100%
    5. Secondary Outcome
    Title Proportion of Drug-related Adverse Events
    Description Proportion of drug-related adverse events
    Time Frame 7 days post treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ivermectin Placebo
    Arm/Group Description Participants on this arm received a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit. (Single dose of STROMECTOL® tablets at 400mcg/kg) Participants on this arm received a single, oral dose of placebo tablets at the enrollment visit. (Placebo tablets did not match ivermectin but they were administered by staff not involved in the clinical care)
    Measure Participants 12 12
    Count of Participants [Participants]
    0
    0%
    0
    0%
    6. Secondary Outcome
    Title Levels of IgG, IgM and IgA
    Description 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]
    Time Frame Up to and including day 28

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Secondary Outcome
    Title Frequency of Innate Immune Cells
    Description 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]
    Time Frame Up to and including day 7

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Secondary Outcome
    Title Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T Cells
    Description 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]
    Time Frame Up to and including day 7

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Secondary Outcome
    Title Results From Cytokine Human Magnetic 30-Plex Panel
    Description 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]
    Time Frame Up to and including day 28

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame 28 days
    Adverse Event Reporting Description Adverse events were assessed at each study visit (days 1, 4, 7, 14, 21 and 28)
    Arm/Group Title Ivermectin Placebo
    Arm/Group Description Participants on this arm received a single, oral dose of ivermectin 400 mcg/kg at the enrolment visit. (Single dose of STROMECTOL® tablets at 400mcg/kg) Participants on this arm received a single, oral dose of placebo tablets at the enrollment visit. (Placebo tablets did not match ivermectin but they were administered by staff not involved in the clinical care)
    All Cause Mortality
    Ivermectin Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/12 (0%) 0/12 (0%)
    Serious Adverse Events
    Ivermectin Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/12 (0%) 0/12 (0%)
    Other (Not Including Serious) Adverse Events
    Ivermectin Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/12 (41.7%) 5/12 (41.7%)
    Blood and lymphatic system disorders
    Leukopenia 0/12 (0%) 0 1/12 (8.3%) 1
    Ferritin elevation 0/12 (0%) 0 1/12 (8.3%) 1
    Hypochromic Microcytic Anemia 1/12 (8.3%) 1 0/12 (0%) 0
    D-Dimer increase 1/12 (8.3%) 1 0/12 (0%) 0
    Cardiac disorders
    Sinus tachycardia 0/12 (0%) 0 1/12 (8.3%) 1
    Dorsal discomfort of a mechanical nature 1/12 (8.3%) 1 0/12 (0%) 0
    Cold Sore 1/12 (8.3%) 1 0/12 (0%) 0
    Gastrointestinal disorders
    Odynophagia 1/12 (8.3%) 1 0/12 (0%) 0
    General disorders
    Hematoma 1/12 (8.3%) 1 1/12 (8.3%) 1
    Infections and infestations
    Acute pharyngitis (tonsillitis) 0/12 (0%) 0 1/12 (8.3%) 1
    Abdominal bacterial translocation 0/12 (0%) 0 1/12 (8.3%) 1
    Nervous system disorders
    Insomnia 0/12 (0%) 0 1/12 (8.3%) 1
    Skin and subcutaneous tissue disorders
    Worsening of acne 1/12 (8.3%) 1 0/12 (0%) 0
    Grade II burn 0/12 (0%) 0 1/12 (8.3%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Carlos Chaccour
    Organization Barcelona Institute for Global Health
    Phone 0034666293112
    Email carlos.chaccour@isglobal.org
    Responsible Party:
    Clinica Universidad de Navarra, Universidad de Navarra
    ClinicalTrials.gov Identifier:
    NCT04390022
    Other Study ID Numbers:
    • SAINT
    First Posted:
    May 15, 2020
    Last Update Posted:
    Dec 17, 2020
    Last Verified:
    Dec 1, 2020