Clinical Trial to Study the Efficacy and Therapeutic Safety of Ivermectin: (SAINTBO)

Study Overview
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Brief Summary
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Coronavirus disease (COVID-19) is an infectious disease caused by a new virus. The disease causes a respiratory illness (such as the flu) with symptoms such as cough, fever, and, in more severe cases, respiratory distress, even developing Acute Respiratory Distress Syndrome, evolving in some cases with the death of the patient. Currently, there are no specific treatments for COVID-19. Currently, there are several ongoing clinical trials evaluating possible treatments. Recently, Leon Caly reports here that Ivermectin, an FDA-approved antiparasitic that was shown to have broad-spectrum antiviral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero cells. hours after infection with SARS-CoV-2 capable of a 5000-fold reduction in viral RNA at 48 h. (1) Ivermectin, therefore, warrants further investigation for possible benefits in humans. The reason for this study is to understand the effect of the drug in eradicating the virus. It is a randomized controlled trial to evaluate the efficacy of Ivermectin in COVID-19. The recruited patient will be assigned to two groups, (1) a group received ivermectin plus care treatment (2) the placebo group plus standard care treatment. The result will be recorded by documenting the RT-PCR reports confirmed at the time of recruitment and at 7 and 14 days within the framework of the study, then they will be adapted to the national care protocol, with 9 scheduled clinical and telemedicine interviews. It will be a randomized controlled trial to be run in RT-PCR confirmed COVID-19 patients who meet the inclusion criteria (asymptomatic/mild to moderate severity). They will be divided into groups after randomization. Group A will be administered one (1) a group received ivermectin plus standard of care treatment (2) the placebo group plus standard of care treatment, along with the existing inpatient and outpatient management clinical guidelines of the hospitals participating in the study, these being adapted to the National standard. The reverse transcriptase-polymerase chain reaction (RT-PCR) will be carried out on days 7 and 14 after the therapeutic intervention and the duration of time at which the RT-PCR becomes negative and/or clinical evolution of the patient will be compared in both study groups. The dose of the drug is not subject to change according to the patient's response or the possible side effect of being administered in a single dose.

Detailed Description
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STUDY DESIGN It is a double-blind, randomized, placebo-controlled superiority trial with two parallel arms. Participants will be randomized to receive a single 600 µg / kg dose of ivermectin or placebo, and the number of patients in the treatment and placebo groups will be in a 2: 1 ratio for the intervention group. The trial statistician will generate the randomization code using blocks of four individuals to ensure the balance between groups. The assignment will be carried out by the main investigator using opaque envelopes, after obtaining informed consent and verification of compliance with all the inclusion and exclusion criteria. The investigational product will be administered by personnel who are not involved in patient care or monitoring of study participants. Participants will be followed up at their homes for a period of 28 days. A patient can discontinue her participation in the study at any time and for any reason. The principal investigator and the panel of experts that make up the safety and adverse effects committee may also withdraw a patient from the study if they believe it is in the best interest of the patient. Serious adverse events (SAEs) related to ivermectin will be followed until they resolve or up to 28 days after the participant's final visit, whichever occurs first. All other SAEs deemed unrelated to ivermectin will be followed up until the participant's final visit or for a specified period at the discretion of the principal investigator. The study will end when the final randomized patient has completed the study, all planned visits have been completed, and inconsistencies in the data have been resolved. OBJECTIVES Primary objective • To explore the efficacy and therapeutic safety of Ivermectin in patients with non-severe and low-risk COVID-19 in the first 72 hours after the onset of symptoms, through the negativization of the polymerase chain in real time. RT-PCR (nasopharyngeal swab) and clinical improvement on day 7 and 28 after treatment, to explore its possible use in the fight against the pandemic. Secondary objectives To evaluate the efficacy of ivermectin in reducing the SARS-CoV-2 viral load in the nasopharyngeal swab on day 7 after treatment. To evaluate the efficacy of ivermectin in improving the progression of symptoms in treated patients. Assess the proportion of seroconversions in patients treated on day 21. Evaluate the safety of ivermectin at the proposed dose. Determine the magnitude of the immune response against SARS-CoV-2 Evaluate the early kinetics of immunity against SARS-CoV-2

Official Title
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Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Therapeutic Safety of Ivermectin Versus Placebo Associated With Standard of Care Treatment in the Early Phase of Coronavirus Infection (COVID19).

Conditions
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Covid19

Intervention / Treatment
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* Drug: Ivermectin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed case of COVID-19 in national reference hospitals - COVID sentinel hospitals. Male and female patients 18 to 75 years (inclusive) of age. Supply of signed and dated informed consent form Declared availability to comply with all study procedures and availability for the duration of the study. In good general health with mild or moderate symptoms during the first week of disease evolution (onset of symptoms maximum 7 days before recruitment). Ability to take oral medications and be willing to adhere to the medication consumption regimen prescribed in the study. The patient must, in the opinion of the principal investigator, be able to comply with all the requirements of the clinical trial (including home monitoring during isolation). The patient is able and willing to comply with the requirements of this test protocol. Voluntarily signed informed consent obtained prior to any proceeding related to the trial. Exclusion Criteria: Known history of ivermectin allergy Hypersensitivity to any component of ivermectin or the excipients of the brand to be used. COVID-19 pneumonia Diagnosed by the treating physician Identified on a chest x-ray Fever or cough present for more than 48 hours. immunoglobulin G (IgG) positive against SARS-CoV-2 by a rapid diagnostic test 8. Recent travel history to loa endemic countries (Angola, Cameroon, Central African Republic, Chad, the Democratic Republic of the Congo, Ethiopia, Equatorial Guinea, Gabon, Republic of the Congo, Nigeria, and Sudan) 9. Current use of quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir, or cobicistat. Use of critical drugs such as warfarin.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, Placebo-controlled parallel clinical trial to Study the efficacy and therapeutic safety of Ivermectin associated with standard of care treatment versus placebo with standard of care treatment in the early phase of coronavirus infection (COVID19). A PHASE II pilot study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ivermectin<br>Participants will receive a single 600 µg / kg dose of ivermectin. | Drug: Ivermectin<br>* Participants will be randomly assigned to receive a single 600 µg / kg dose of ivermectin or placebo.<br>* Other names: A;|
| Placebo Comparator: Placebo Comparator<br>Participants will receive a single dose of placebo. | Drug: Placebo<br>* Participants will be randomly assigned to receive a single of placebo.<br>* Other names: B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of viral load | A comparison will be made between the initial viral load before the dose of ivermectin with respect to the viral load on the third day after the administration of the drug. The primary outcome of interest will be the correlation between the use of a treatment regimen containing Ivermectin plus the standard of care, with the endpoint of measurement relative to the difference in viral loads. | 3 days | 
| Clinical remission | Clinical remission, defined as a remission of all the patient's symptoms based on the clinical management protocol. The primary outcome of interest will be the correlation between the use of a treatment regimen containing Ivermectin plus the standard of care, initiated early after the confirmed diagnosis of COVID-19 with the endpoint of measurement relative to the difference in clinical evolution. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical signs of toxicity | The secondary outcome of interest will be the correlation between these treatment regimens and the appearance of clinical signs of toxicity or adverse effects (defined as the first clinical or laboratory finding of a neurological, hepatic, renal, hematological, or pancreatic alteration, or verification of alterations in pupillometry during the outpatient clinical course or hospitalization. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Efficacy, Safety, Ivermectin