SAINT: Sars-CoV-2/COVID-19 Ivermectin Navarra-ISGlobal Trial
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A final study visit will be made for participants who withdraw prematurely from the study or are withdrawn by the investigator.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
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:
|
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
- 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
- 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).
- 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
- 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]
- 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]
Eligibility Criteria
Criteria
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.
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.- SAINT
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
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%
|
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
|
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%
|
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%
|
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%
|
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 |
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 |
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 |
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
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 |
carlos.chaccour@isglobal.org |
- SAINT