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

Covid19 Clinical Trial

— SAINT-PERU  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04635943
• Other study ID #: EC-CNTEI-014-2020
• Status: Completed
• Phase: Phase 2
• Start date: August 29, 2020
• Est. completion date: April 30, 2021

Study information

• Verified date: March 2021
• Source: Universidad Peruana Cayetano Heredia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 186
• Est. completion date: April 30, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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)

Related Conditions & MeSH terms

• Communicable Diseases
• Coronavirus Infection
• Coronavirus Infections
• COVID-19
• Covid19
• Infections
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

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).
• Placebo
The placebo presentation will be an oral drop solution undistinguishable from ivermectin, but without this device pharmaceutical ingredient.

Locations

Country	Name	City	State
Peru	Hospital Nacional Cayetano Heredia	Lima

Sponsors (2)

Lead Sponsor	Collaborator
Universidad Peruana Cayetano Heredia	Barcelona Institute for Global Health

Country where clinical trial is conducted

Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	7 days post-treatment
Secondary	Mean viral load	Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab	Baseline and on days 4, 7, 14 and 21
Secondary	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
Secondary	Seroconversion at day 21	Proportion of participants with positive IgG at day 21	Up to and including day 21
Secondary	Proportion of drug-related adverse events	Proportion of drug-related adverse events	7 days post treatment
Secondary	Levels of IgG, IgM and IgA		Up to and including day 21
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	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	Up to and including day 7
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)-a, IFN-?, interleukin (IL)-1RA, IL-1ß, 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-? induced protein (IP-10), monocyte chemoattractant protein (MCP-1), monokine induced by IFN-? (MIG), macrophage inflammatory protein (MIP)-1a, MIP-1ß 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
Secondary	Presence of intestinal helminths	Proportion and parasitic load of intestinal helminths by spontaneous sedimentation method.	Baseline and on day 14.