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

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Covid-19; Coronavirus Infection; SARS-CoV-2 Infection
• Interventions: Drug: Ivermectin; Drug: Placebo
• Enrollment: 24

Participant Flow

Recruitment Details
Pre-assignment Details

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 Number of Baseline Participants		12	12	24
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	12 participants	12 participants	24 participants
		26; (19 to 36)	26; (21 to 44)	26; (20 to 40)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	24 participants
	Female	5 41.7%	7 58.3%	12 50.0%
	Male	7 58.3%	5 41.7%	12 50.0%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants	0 participants	0 participants
				0
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Body mass index; Median (Inter-Quartile Range); Unit of measure: Kg/m^2
	Number Analyzed	12 participants	12 participants	24 participants
		23.5; (19.6 to 27.8)	22.9; (21.0 to 24.8)	22.9; (20.6 to 26.1)
Any symptoms; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	24 participants
		12 100.0%	12 100.0%	24 100.0%
Earliest start of any symptom [1]; Median (Inter-Quartile Range); Unit of measure: Hours
	Number Analyzed	12 participants	12 participants	24 participants
		24; (24 to 48)	48; (36 to 48)	48; (24 to 48)
		[1] Measure Description: Presence of symptoms as well as their onset date was self-reported by each patient in the baseline visit.
Fever; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	24 participants
		7 58.3%	9 75.0%	16 66.7%
Earliest start of fever [1] [2]; Median (Inter-Quartile Range); Unit of measure: Hours
	Number Analyzed	7 participants	9 participants	16 participants
		24; (12 to 24)	24; (24 to 48)	24; (15 to 36)
		[1] Measure Description: Presence of fever as well as its onset date was self-reported by each patient in the baseline visit.; [2] Measure Analysis Population Description: Only patients with reported fever
Cough; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	24 participants
		4 33.3%	2 16.7%	6 25.0%
Earliest start of cough [1] [2]; Median (Inter-Quartile Range); Unit of measure: Hours
	Number Analyzed	4 participants	2 participants	6 participants
		24; (16 to 36)	10; (8 to 12)	18; (8 to 24)
		[1] Measure Description: Presence of cough as well as its onset date was self-reported by each patient in the baseline visit.; [2] Measure Analysis Population Description: Only patients with cough.
CRP; Median (Inter-Quartile Range); Unit of measure: mg/dL
	Number Analyzed	12 participants	12 participants	24 participants
		0.3; (0.2 to 0.8)	0.3; (0.2 to 0.6)	0.3; (0.2 to 0.7)
Ferritin; Median (Inter-Quartile Range); Unit of measure: mg/dL
	Number Analyzed	12 participants	12 participants	24 participants
		165.0; (95.8 to 241.3)	156.1; (103.1 to 223.0)	160.9; (101.8 to 223.0)
IL-6; Median (Inter-Quartile Range); Unit of measure: pg/mL
	Number Analyzed	12 participants	12 participants	24 participants
		6.5; (5.1 to 9.6)	4.5; (3.0 to 6.5)	5.3; (3.8 to 8.2)
D-Dimer; Median (Inter-Quartile Range); Unit of measure: ng/mL
	Number Analyzed	12 participants	12 participants	24 participants
		295; (270 to 420)	280; (270 to 315)	285; (270 to 365)

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)
Overall Number of Participants Analyzed	12	12
Measure Type: Count of Participants; Unit of Measure: Participants
PCR positivity (gene N)	12 100.0%	12 100.0%
PCR positivity (gene E)	11 91.7%	12 100.0%

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)
Overall Number of Participants Analyzed	12	12
Median (Inter-Quartile Range); Unit of Measure: copies/mL
Gene E - day 1	16850000; (5915000 to 385250000)	26700000; (8325000 to 423500000)
Gene E - day 4	161000; (2820 to 878000)	493500; (103700 to 9910000)
Gene E - day 7	1018; (92 to 15445)	23550; (709 to 226500)
Gene E - day 14	7; (0 to 42)	30; (1 to 50)
Gene E - day 21	1; (0 to 9)	0; (0 to 16)
Gene N - day 1	367000000; (18350000 to 9280000000)	327500000; (58300000 to 6740000000)
Gene N - day 4	269000; (1885 to 1046500)	2194500; (73150 to 37100000)
Gene N - day 7	2255; (938 to 34650)	36800; (4510 to 630500)
Gene N - day 14	86; (0 to 1235)	75; (24 to 710)
Gene N - day 21	0; (0 to 67)	107; (0 to 183)

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)
Overall Number of Participants Analyzed	12	12
Measure Type: Count of Participants; Unit of Measure: Participants
Fever - Day 4	0 0.0%	0 0.0%
Fever - Day 7	1 8.3%	0 0.0%
Fever - Day 14	0 0.0%	0 0.0%
Fever - Day 21	0 0.0%	0 0.0%
Cough - Day 4	5 41.7%	6 50.0%
Cough - Day 7	5 41.7%	5 41.7%
Cough - Day 14	1 8.3%	3 25.0%
Cough - Day 21	1 8.3%	3 25.0%

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)
Overall Number of Participants Analyzed	12	12
Measure Type: Count of Participants; Unit of Measure: Participants
	12 100.0%	12 100.0%

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)
Overall Number of Participants Analyzed	12	12
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	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 Not Reported

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 Not Reported

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 Not Reported

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 Not Reported

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 (%)		Affected / at Risk (%)
Total	0/12 (0.00%)		0/12 (0.00%)
Serious Adverse Events
	Ivermectin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0.00%)		0/12 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Ivermectin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.67%)		5/12 (41.67%)
Blood and lymphatic system disorders
Leukopenia †	0/12 (0.00%)	0	1/12 (8.33%)	1
Ferritin elevation †	0/12 (0.00%)	0	1/12 (8.33%)	1
Hypochromic Microcytic Anemia †	1/12 (8.33%)	1	0/12 (0.00%)	0
D-Dimer increase †	1/12 (8.33%)	1	0/12 (0.00%)	0
Cardiac disorders
Sinus tachycardia †	0/12 (0.00%)	0	1/12 (8.33%)	1
Dorsal discomfort of a mechanical nature †	1/12 (8.33%)	1	0/12 (0.00%)	0
Cold Sore †	1/12 (8.33%)	1	0/12 (0.00%)	0
Gastrointestinal disorders
Odynophagia †	1/12 (8.33%)	1	0/12 (0.00%)	0
General disorders
Hematoma †	1/12 (8.33%)	1	1/12 (8.33%)	1
Infections and infestations
Acute pharyngitis (tonsillitis) †	0/12 (0.00%)	0	1/12 (8.33%)	1
Abdominal bacterial translocation †	0/12 (0.00%)	0	1/12 (8.33%)	1
Nervous system disorders
Insomnia †	0/12 (0.00%)	0	1/12 (8.33%)	1
Skin and subcutaneous tissue disorders
Worsening of acne †	1/12 (8.33%)	1	0/12 (0.00%)	0
Grade II burn †	0/12 (0.00%)	0	1/12 (8.33%)	1
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

Results Point of Contact

• Name/Title: Carlos Chaccour
• Organization: Barcelona Institute for Global Health
• Phone: 0034666293112
• EMail: carlos.chaccour@isglobal.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chaccour C, Casellas A, Blanco-Di Matteo A, Pineda I, Fernandez-Montero A, Ruiz-Castillo P, Richardson MA, Rodríguez-Mateos M, Jordán-Iborra C, Brew J, Carmona-Torre F, Giráldez M, Laso E, Gabaldón-Figueira JC, Dobaño C, Moncunill G, Yuste JR, Del Pozo JL, Rabinovich NR, Schöning V, Hammann F, Reina G, Sadaba B, Fernández-Alonso M. The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial. EClinicalMedicine. 2021 Jan 19:100720. doi: 10.1016/j.eclinm.2020.100720. [Epub ahead of print]

• Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
• ClinicalTrials.gov Identifier: NCT04390022
• Other Study ID Numbers: SAINT
• First Submitted: May 7, 2020
• First Posted: May 15, 2020
• Results First Submitted: December 9, 2020
• Results First Posted: December 17, 2020
• Last Update Posted: December 17, 2020