Clinical trial NCT04894721: Prophylaxis for COVID-19: Ivermectin in Close Contacts of COVID-19 Cases (IVERNEX-TUC)
Official title: Study of Efficacy and Safety of Ivermectin for COVID-19 Prophylaxis in Post-exposure Contact or Epidemiological Link
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Covid19
Keywords: Ivermectin
Prophylaxis
COVID-19
Epidemiological link
Lead sponsor: Ministry of Public Health, Argentina
Sponsor class: OTHER_GOV
First posted: 2021-05-20
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled. Experimental and Control Group in relationship of 2:1
Primary purpose: PREVENTION

Brief summary: Randomized controlled clinical trial on using oral ivermectin in COVID-19 prophylaxis supplying the drug to close contacts of confirmed cases.

Detailed description: This is a randomized, double-blind, and controlled clinical trial that aims to evaluate the use of oral ivermectin in COVID-19 prophylaxis. The study has two arms in a relationship of 2:1: Experimental Group (EG n=500) and Placebo Group (CG n=250).

The sample size was calculated by applying a two-proportion comparison test. Type of two-sided test, 95% confidence or safety level (1-α), 95% statistical power, 75% P1 (proportion in the placebo group), 65% P2 (proportion in the new treatment or intervention group), size sample without adjustment (n = 543), 25% expected proportion of losses, n= 724 sample adjusted for losses.

The hypothesis of the study is that treatment with ivermectin may decrease the chance of occurrence/progress of clinical manifestations and onset of severe disease. Whereas control of the contagion on the first days of development of the disease, this treatment with ivermectin in suspected cases of COVID-19 (by epidemiological nexus) would contribute to the control of contagion at the first part of the infection, even in the absence of symptoms.

Categorical variables will be represented with frequencies and proportions, while continuous quantitative variables will be expressed as mean ± standard deviation (SD) or as median and interquartile range (IQR). The proportions will be compared using Pearson's Chi-square test or Fisher's exact test as appropriate, and continuous quantitative variables with Student's t test. The estimation of the efficacy of intensive treatment with Ivermectin will be calculated using Kaplan-Meier curves and the differences will be analyzed by means of the log-rank test. The risk will be calculated as a ratio of advantages for Intensive treatment with Ivermectin (Odds Ratio, OR) with its 95% confidence intervals (95% CI). A value of p \<0.05 will be considered significant. Analyzes will be performed using Stata 11.2 software.

Eligibility criteria: Inclusion Criteria:

* Over 18 years either sex
* Women of childbearing age with a negative pregnancy test
* In close contact group or epidemiological nexus of a positive COVID-19 case
* Able to understand and grant informed consent
* Real-time - polymerase chain reaction test with a negative result

Exclusion Criteria:

* Known hypersensitivity or allergy to any component of the drug under evaluation
* Age under 18 years
* Use of immunosuppressants (including systemic corticosteroids) in the last 30 days
* Pregnant or lactating
* Patients with other acute infectious diseases
* Patients with autoimmune disease and/or chronic decompensated diseases
* Who have received a vaccine for COVID-19 (1/2 dose) or that have taken ivermectin (prior to 30 days of the study) or who are participating in another COVID-19 prophylaxis study

Primary outcomes:
measure: Number of subjects who were diagnosed with COVID-19 in EG and CG (Negative polymerase chain reaction - real-time).
timeFrame: At 2 weeks
Secondary outcomes:
measure: Contagion risk.
timeFrame: Up to 2 weeks
measure: Prophylactic effect associated with patient's preexisting comorbidity
timeFrame: Up to 2 weeks
Other outcomes:
Locations:
city: Tucumán
country: Argentina
facility: SI.PRO.SA, Ministerio de Salud Pública
Study officials:
affiliation: Ministry of Public Health, Tucumán, Argentina
name: Rossana Chahla, Ph. D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chong CR, Sullivan DJ Jr. New uses for old drugs. Nature. 2007 Aug 9;448(7154):645-6. doi: 10.1038/448645a. No abstract available.
citation: Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun;178:104787. doi: 10.1016/j.antiviral.2020.104787. Epub 2020 Apr 3.
citation: Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, Phru CS, Rahman M, Zaman K, Somani J, Yasmin R, Hasnat MA, Kabir A, Aziz AB, Khan WA. A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. Int J Infect Dis. 2021 Feb;103:214-216. doi: 10.1016/j.ijid.2020.11.191. Epub 2020 Dec 2.
citation: Ahmed Elgazzar, Basma Hany, Shaimaa Abo Youssef et al. Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic, 13 November 2020, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-100956/v1]
citation: Hirsch RR, Carvallo, Héctor E. Ivermectin as Prophylaxis Against COVID-19 Retrospective Cases Evaluation. Microbiol Infect Dis. 2020; 4(4): 1-8.