Coronavirus Infection, Covid-19, SARS-CoV-2 Infection
Conditions
Keywords
ivermectin
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 A final study visit will be made for participants who withdraw prematurely from the study or are withdrawn by the investigator.
Interventions
DRUGIvermectin
Single dose of STROMECTOL® tablets at 400mcg/kg
DRUGPlacebo
Placebo tablets will not match ivermectin but they will be administered by staff not involved in the clinical care.
Sponsors
Barcelona Institute for Global Health
Clinica Universidad de Navarra, Universidad de Navarra
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blind
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Fever and Cough Progression | Days 4, 7, 14 and 21 | Proportion of patients with fever and cough |
| Seroconversion at Day 21 | Up to and including day 21 | Proportion of participants with positive IgG at day 21 |
| Proportion of Drug-related Adverse Events | 7 days post treatment | Proportion of drug-related adverse events |
| 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. \[Results not yet available\] |
| 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. \[Results not yet available\] |
| 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). \[Results not yet available\] |
| 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. \[Results not yet available\] |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ivermectin 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) | 12 |
| Placebo 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) | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Ivermectin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 26 years | 26 years | 26 years |
| Any symptoms | 12 Participants | 12 Participants | 24 Participants |
| Body mass index | 23.5 kg/m^2 | 22.9 kg/m^2 | 22.9 kg/m^2 |
| Cough | 4 Participants | 2 Participants | 6 Participants |
| CRP | 0.3 mg/dL | 0.3 mg/dL | 0.3 mg/dL |
| D-Dimer | 295 ng/mL | 280 ng/mL | 285 ng/mL |
| Earliest start of any symptom | 24 hours | 48 hours | 48 hours |
| Earliest start of cough | 24 hours | 10 hours | 18 hours |
| Earliest start of fever | 24 hours | 24 hours | 24 hours |
| Ferritin | 165.0 mg/dL | 156.1 mg/dL | 160.9 mg/dL |
| Fever | 7 Participants | 9 Participants | 16 Participants |
| IL-6 | 6.5 pg/mL | 4.5 pg/mL | 5.3 pg/mL |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 5 / 12 | 5 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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).
Time frame: 7 days post-treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ivermectin | Proportion of Patients With a Positive SARS-CoV-2 PCR | PCR positivity (gene N) | 12 Participants |
| Ivermectin | Proportion of Patients With a Positive SARS-CoV-2 PCR | PCR positivity (gene E) | 11 Participants |
| Placebo | Proportion of Patients With a Positive SARS-CoV-2 PCR | PCR positivity (gene N) | 12 Participants |
| Placebo | Proportion of Patients With a Positive SARS-CoV-2 PCR | PCR positivity (gene E) | 12 Participants |
Secondary
Fever and Cough Progression
Proportion of patients with fever and cough
Time frame: Days 4, 7, 14 and 21
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ivermectin | Fever and Cough Progression | Fever - Day 4 | 0 Participants |
| Ivermectin | Fever and Cough Progression | Fever - Day 21 | 0 Participants |
| Ivermectin | Fever and Cough Progression | Fever - Day 7 | 1 Participants |
| Ivermectin | Fever and Cough Progression | Fever - Day 14 | 0 Participants |
| Ivermectin | Fever and Cough Progression | Cough - Day 4 | 5 Participants |
| Ivermectin | Fever and Cough Progression | Cough - Day 7 | 5 Participants |
| Ivermectin | Fever and Cough Progression | Cough - Day 14 | 1 Participants |
| Ivermectin | Fever and Cough Progression | Cough - Day 21 | 1 Participants |
| Placebo | Fever and Cough Progression | Cough - Day 21 | 3 Participants |
| Placebo | Fever and Cough Progression | Cough - Day 4 | 6 Participants |
| Placebo | Fever and Cough Progression | Fever - Day 21 | 0 Participants |
| Placebo | Fever and Cough Progression | Fever - Day 4 | 0 Participants |
| Placebo | Fever and Cough Progression | Cough - Day 14 | 3 Participants |
| Placebo | Fever and Cough Progression | Fever - Day 7 | 0 Participants |
| Placebo | Fever and Cough Progression | Cough - Day 7 | 5 Participants |
| Placebo | Fever and Cough Progression | Fever - Day 14 | 0 Participants |
Secondary
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. \[Results not yet available\]
Time frame: Up to and including day 7
Secondary
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. \[Results not yet available\]
Time frame: Up to and including day 7
Secondary
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. \[Results not yet available\]
Time frame: Up to and including day 28
Secondary
Median Viral Load
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ivermectin | Median Viral Load | Gene E - day 1 | 16850000 copies/mL |
| Ivermectin | Median Viral Load | Gene E - day 4 | 161000 copies/mL |
| Ivermectin | Median Viral Load | Gene E - day 7 | 1018 copies/mL |
| Ivermectin | Median Viral Load | Gene E - day 14 | 7 copies/mL |
| Ivermectin | Median Viral Load | Gene E - day 21 | 1 copies/mL |
| Ivermectin | Median Viral Load | Gene N - day 1 | 367000000 copies/mL |
| Ivermectin | Median Viral Load | Gene N - day 4 | 269000 copies/mL |
| Ivermectin | Median Viral Load | Gene N - day 7 | 2255 copies/mL |
| Ivermectin | Median Viral Load | Gene N - day 14 | 86 copies/mL |
| Ivermectin | Median Viral Load | Gene N - day 21 | 0 copies/mL |
| Placebo | Median Viral Load | Gene N - day 7 | 36800 copies/mL |
| Placebo | Median Viral Load | Gene E - day 1 | 26700000 copies/mL |
| Placebo | Median Viral Load | Gene N - day 1 | 327500000 copies/mL |
| Placebo | Median Viral Load | Gene E - day 4 | 493500 copies/mL |
| Placebo | Median Viral Load | Gene N - day 21 | 107 copies/mL |
| Placebo | Median Viral Load | Gene E - day 7 | 23550 copies/mL |
| Placebo | Median Viral Load | Gene N - day 4 | 2194500 copies/mL |
| Placebo | Median Viral Load | Gene E - day 14 | 30 copies/mL |
| Placebo | Median Viral Load | Gene N - day 14 | 75 copies/mL |
| Placebo | Median Viral Load | Gene E - day 21 | 0 copies/mL |
Secondary
Proportion of Drug-related Adverse Events
Proportion of drug-related adverse events
Time frame: 7 days post treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ivermectin | Proportion of Drug-related Adverse Events | 0 Participants |
| Placebo | Proportion of Drug-related Adverse Events | 0 Participants |
Secondary
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). \[Results not yet available\]
Time frame: Up to and including day 28
Secondary
Seroconversion at Day 21
Proportion of participants with positive IgG at day 21
Time frame: Up to and including day 21
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ivermectin | Seroconversion at Day 21 | 12 Participants |
| Placebo | Seroconversion at Day 21 | 12 Participants |