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)

• ClinicalTrials.gov Identifier: NCT04635943
• Recruitment Status: Completed
• First Posted: November 19, 2020
• Last Update Posted: December 6, 2021
• Sponsor: Universidad Peruana Cayetano Heredia
• Collaborator: Barcelona Institute for Global Health
• Information provided by (Responsible Party): Universidad Peruana Cayetano Heredia

Tracking Information

• First Submitted Date: November 9, 2020
• First Posted Date: November 19, 2020
• Last Update Posted Date: December 6, 2021
• Actual Study Start Date: August 29, 2020
• Actual Primary Completion Date: April 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 18, 2020)

Proportion of patients with a positive SARS-CoV-2 PCR. [ Time Frame: 7 days post-treatment ]

Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 15, 2021)

• Mean viral load [ Time Frame: Baseline and on days 4, 7, 14 and 21 ]
  Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab
• Fever and cough progression [ Time Frame: Up to and including day 21 ]
  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
• Seroconversion at day 21 [ Time Frame: Up to and including day 21 ]
  Proportion of participants with positive IgG at day 21
• Proportion of drug-related adverse events [ Time Frame: 7 days post treatment ]
  Proportion of drug-related adverse events
• Levels of IgG, IgM and IgA [ Time Frame: Up to and including day 21 ]
• Frequency of innate immune cells [ Time Frame: 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
• Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T cells [ Time Frame: 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 from cytokine Human Magnetic 30-Plex Panel [ Time Frame: Up to and including day 21 ]
  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)
• Presence of intestinal helminths [ Time Frame: Baseline and on day 14. ]
  Proportion and parasitic load of intestinal helminths by spontaneous sedimentation method.

Original Secondary Outcome Measures (submitted: November 18, 2020)

• Mean viral load [ Time Frame: Baseline and on days 4, 7, 14 and 21 ]
  Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab
• Fever and cough progression [ Time Frame: Up to and including day 21 ]
  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
• Seroconversion at day 21 [ Time Frame: Up to and including day 21 ]
  Proportion of participants with positive IgG at day 21
• Proportion of drug-related adverse events [ Time Frame: 7 days post treatment ]
  Proportion of drug-related adverse events
• Levels of IgG, IgM and IgA [ Time Frame: Up to and including day 21 ]
• Frequency of innate immune cells [ Time Frame: 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
• Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T cells [ Time Frame: 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 from cytokine Human Magnetic 30-Plex Panel [ Time Frame: Up to and including day 21 ]
  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)
• Presence of intestinal helminths [ Time Frame: Baseline and on day 14. ]
  Proportion and parasitic load of intestinal helminths by quantitative Kato-katz and Baerman method

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

SAINT-PERU is a triple-blinded, randomized, placebo-controlled trial with two parallel arms to evaluate the efficacy of one daily dose of ivermectin during three consecutive days, administered to patients with a positive PCR test for SARS-CoV-2 in a nasopharyngeal specimen, symptomatic for 96 hours or less, with non-severe COVID-19 disease at baseline, regardless of the presence of risk factors for progression to severity. The efficacy of the drug-based strategy to reduce or block transmission involves treating during early phases of infection, when viral replication is yet limited.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

The Ivermectin presentation will be an oral drop solution in a flasks containing 5ml. The placebo presentation will also be an oral drop solution, undistinguishable from ivermectin, but without this device pharmaceutical ingredient. The pharmacist will prepare the treatment flasks (three 5ml flasks per participant), labelling them according to the randomization list in blocks of four (a, b) previously prepared by the epidemiologist, and according to the randomized treatment allocation previously notified by the principal investigator. The participant, investigator and outcomes assessor will be blinded to the study intervention.

Primary Purpose: Treatment

Condition

• Covid19
• Coronavirus Infection
• SARS-CoV Infection

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

Study Arms

• 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.
  Intervention: Drug: Ivermectin
• 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.
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 15, 2021): 186
• Original Estimated Enrollment (submitted: November 18, 2020): 68
• Actual Study Completion Date: April 30, 2021
• Actual Primary Completion Date: April 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Peru

Administrative Information

• NCT Number: NCT04635943
• Other Study ID Numbers: EC-CNTEI-014-2020
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Universidad Peruana Cayetano Heredia
• Original Responsible Party: Same as current
• Current Study Sponsor: Universidad Peruana Cayetano Heredia
• Original Study Sponsor: Same as current
• Collaborators: Barcelona Institute for Global Health
• Investigators: Not Provided
• PRS Account: Universidad Peruana Cayetano Heredia
• Verification Date: March 2021