Randomized Phase IIA Clinical Trial to Evaluate the Efficacy of Ivermectin to Obtain Negative PCR Results in Patients With Early Phase COVID-19 (SAINT-PERU)

SAINT-PERU is a triple-blinded, randomized placebo-controlled trial with two parallel arms to evaluate the efficacy of ivermectin in negativizing nasopharyngeal PCR in patients with SARS-CoV-2 infection. The trial is conducted in two national hospitals at Lima-Peru.

Study Overview

• Status: Completed
• Conditions: Coronavirus Infection; Covid19; SARS-CoV Infection
• Intervention / Treatment: Drug: Ivermectin; Drug: Placebo

Detailed Description

SAINT is a triple-blinded, randomized placebo-controlled trial with two parallel arms to evaluate the efficacy of ivermectin in negativizing nasopharyngeal PCR in patients with SARS-CoV-2 infection. The trial is conducted in two national hospitals at Lima-Peru.

The planned sample size is 186 SARS-CoV-2 PCR positive patients: 93 patients to treatment and 93 to the placebo group. Participants will be randomized to receive one dose of 300 mcg/kg ivermectin or placebo daily for three consecutive days. The epidemiologist will generate a list of correlative numbers, in randomized blocks of size 4, with the assignment to the treatment groups (a and b). The randomization list will be kept in an encrypted file accessible only to the trial statistician. This list will be handed directly to the pharmacist. Independently, the principal investigator will randomly assign the intervention (ivermectin) to one of the two groups (a or b) by tossing a coin, and will inform the pharmacist of the result of this process. The pharmacist will prepare and label the treatment vials according to the randomization list prepared by the epidemiologist and the treatment assignment given by the principal investigator. Eligible patients will be allocated in a 1:1 ratio using this randomization list.

Participants are expected to remain in the trial for a period of 21 days.

In the interests of public health and containing transmission of infection, follow-up visits will be conducted by the trial medical staff at the participant's home or at a hospital in case of hospitalization.

Follow-up visits will assess clinical and laboratory parameters of the patients.

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 2

Contacts and Locations

Study Locations

• Peru
  • Lima, Peru, 15103
    • Hospital Nacional Cayetano Heredia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with COVID-19 typical symptoms (cough, fever, anosmia) present for not more than 96 hours.
2. 18 years or older.
3. No use of ivermectin prior to the study.
4. No known history of ivermectin allergy.
5. The patient can give his consent to take part in the study.
6. Not 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.

Exclusion Criteria:

1. COVID-19 pneumonia

   • Diagnosed by the attending physician (oxygen saturation < 95% or lung crackles)
2. Positive pregnancy test for women of childbearing age*
3. Positive IgG against SARS-CoV-2 by rapid diagnostic test.

4. Negative SARS-CoV-2 PCR from a nasopharyngeal swab.

   • Women of child bearing age may participate if they use a safe contraceptive method for the entire period of the study. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ivermectin; Participants on this arm will receive orally one (1) daily dose of ivermectin 300 mcg/kg for three (3) consecutive days, starting at the enrolment visit.	Drug: Ivermectin; One daily dose of NOXAL-Ivermectin Oral Solution (6 mg/mL) at 300mcg/kg for three (3) consecutive days. A weight-equivalence table will be used to determine each participant´s dose (number of oral drops/day).; Other Names: Noxal
Placebo Comparator: Placebo; Participants on this arm will receive orally one (1) daily dose of placebo for three (3) consecutive days, starting at the enrolment visit.	Drug: Placebo; The placebo presentation will be an oral drop solution undistinguishable from ivermectin, but without this device pharmaceutical ingredient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	7 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean viral load	Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab	Baseline and on days 4, 7, 14 and 21
Fever and cough progression	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	Up to and including day 21
Seroconversion at day 21	Proportion of participants with positive IgG at day 21	Up to and including day 21
Proportion of drug-related adverse events	Proportion of drug-related adverse events	7 days post treatment
Levels of IgG, IgM and IgA		Up to and including day 21
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	Up to and including day 7
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	Up to and including day 7
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)	Up to and including day 21
Presence of intestinal helminths	Proportion and parasitic load of intestinal helminths by spontaneous sedimentation method.	Baseline and on day 14.

Collaborators and Investigators

• Sponsor: Universidad Peruana Cayetano Heredia
• Collaborators: Barcelona Institute for Global Health

Publications and helpful links

General Publications

• Garcia PJ, Mundaca H, Ugarte-Gil C, Leon P, Malaga G, Chaccour C, Carcamo CP. Randomized clinical trial to compare the efficacy of ivermectin versus placebo to negativize nasopharyngeal PCR in patients with early COVID-19 in Peru (SAINT-Peru): a structured summary of a study protocol for randomized controlled trial. Trials. 2021 Apr 9;22(1):262. doi: 10.1186/s13063-021-05236-2.

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2020
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): April 30, 2021

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): December 6, 2021
• Last Update Submitted That Met QC Criteria: December 3, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Infections; Communicable Diseases; Anti-Infective Agents; Antiparasitic Agents; Ivermectin
• Other Study ID Numbers: EC-CNTEI-014-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No