Clinical trial NCT04635943: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Coronavirus Infection
SARS-CoV Infection
Lead sponsor: Universidad Peruana Cayetano Heredia
Sponsor class: OTHER
Collaborators: name: Barcelona Institute for Global Health
First posted: 2020-11-19
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Proportion of patients with a positive SARS-CoV-2 PCR.
timeFrame: 7 days post-treatment
Secondary outcomes:
measure: Mean viral load
timeFrame: Baseline and on days 4, 7, 14 and 21
measure: Fever and cough progression
timeFrame: Up to and including day 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 21
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 21
measure: Presence of intestinal helminths
timeFrame: Baseline and on day 14.
Other outcomes:
Locations:
city: Lima
country: Peru
facility: Hospital Nacional Cayetano Heredia
Study officials:
References:
citation: 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.