Clinical trial NCT04390022: Sars-CoV-2/COVID-19 Ivermectin Navarra-ISGlobal Trial
Official title: Pilot Study to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid-19
Coronavirus Infection
SARS-CoV-2 Infection
Keywords: ivermectin
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
Collaborators: name: Barcelona Institute for Global Health
First posted: 2020-05-15
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Patients diagnosed with COVID-19 in the emergency room of the Clínica Universidad de Navarra with a positive SARS-CoV-2 PCR.
2. Residents of the Pamplona basin ("Cuenca de Pamplona")
3. The patient should be aged 18 to 59 years
4. Negative pregnancy test for women of child bearing age\*
5. The patient or his/her representative, have given consent to participate in the study.
6. 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:

1. Known history of Ivermectin allergy
2. Hypersensitivity to any component of Stromectol®
3. COVID-19 Pneumonia

   * Diagnosed by the attending physician
   * Identified in a chest X-ray
4. Fever or cough present for more than 48 hours
5. Positive IgG against SARS-CoV-2 by rapid test
6. Age under 18 or over 60 years
7. 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
8. 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)
9. 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.

Primary outcomes:
measure: Proportion of Patients With a Positive SARS-CoV-2 PCR
timeFrame: 7 days post-treatment
Secondary outcomes:
measure: Median Viral Load
timeFrame: Baseline and on days 4, 7, 14 and 21
measure: Fever and Cough Progression
timeFrame: Days 4, 7, 14 and 21
measure: Seroconversion at Day 21
timeFrame: Up to and including day 21
measure: Proportion of Drug-related Adverse Events
timeFrame: 7 days post treatment
measure: Levels of IgG, IgM and IgA
timeFrame: Up to and including day 28
measure: Frequency of Innate Immune Cells
timeFrame: Up to and including day 7
measure: Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T Cells
timeFrame: Up to and including day 7
measure: Results From Cytokine Human Magnetic 30-Plex Panel
timeFrame: Up to and including day 28
Other outcomes:
Locations:
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
Study officials:
affiliation: Clinica Universidad de Navarra and Barcelona Institute of Global Health
name: Carlos J Chaccour, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chaccour C, Casellas A, Blanco-Di Matteo A, Pineda I, Fernandez-Montero A, Ruiz-Castillo P, Richardson MA, Rodriguez-Mateos M, Jordan-Iborra C, Brew J, Carmona-Torre F, Giraldez M, Laso E, Gabaldon-Figueira JC, Dobano C, Moncunill G, Yuste JR, Del Pozo JL, Rabinovich NR, Schoning V, Hammann F, Reina G, Sadaba B, Fernandez-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 Feb;32:100720. doi: 10.1016/j.eclinm.2020.100720. Epub 2021 Jan 19.