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It is a single-center, prospective, randomized, double-blind, placebo-controlled study carried out by the Ministry of Public Health of the Province of Corrientes, Argentina, in coordination with the Corrientes Institute of Cardiology "Juana F. Cabral". Patients who meet all the inclusion criteria and none of the exclusion criteria are randomized via the web system to receive placebo or ivermectin. The need for hospitalization in patients with COVID-19 is assessed as the primary end point. As secondary end points are evaluated: time to hospitalization (in days); use of invasive mechanical ventilation; time to invasive mechanical ventilation (in days); dialysis; all-cause mortality; negative of the swab at 3 ± 1 days and 12 ± 2 days after entering the study and ivermectin safety.
Intermediate internal analyzes of study objectives and serious adverse events will be performed, including 125; 250 and 375 patients in order to assess the possible need for early termination of the study. For these intermediate internal analyzes, the Haybittle-Peto rule will be followed, therefore a value of p <0.001 will be considered significant
The study will be carried out in the province of Corrientes, in the Argentine Republic. All patients must be domiciled in this province. In the province of Corrientes, the care of patients with COVID19 is in charge of a single group of professionals (Crisis Committee) and patients who require hospitalization will be carried out in a single hospital destined for this purpose
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ivermectin | Active Comparator | The dose of ivermectin in patients who are randomized to the active substance depends on the weight of the patient: More than 48 kg and less than 80 kg: Two tablets of 6 mg each (12 mg in total) at the time of inclusion and the same dose at 24 hours. More than 80 kg and less than 110 kg: Three tablets of 6 mg each (18 mg in total) at the time of inclusion and the same dose at 24 hours. More than 110 Kg: Four tablets of 6 mg each (24 mg in total) at the time of inclusion and the same dose at 24 hours. |
|
| Placebo | Placebo Comparator | The dose of placebo in patients who are randomized to the this depends on the weight of the patient: More than 48 kg and less than 80 kg: Two tablets of 6 mg each (12 mg in total) at the time of inclusion and the same dose at 24 hours. More than 80 kg and less than 110 kg: Three tablets of 6 mg each (18 mg in total) at the time of inclusion and the same dose at 24 hours. More than 110 Kg: Four tablets of 6 mg each (24 mg in total) at the time of inclusion and the same dose at 24 hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ivermectin | Drug | Patients will receive the tablet from the branch to which they were randomized only at the time of inclusion and 24 hours after the first dose. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Hospitalization of medical cause in patients with COVID-19 in each arm | Hospitalization will be considered when at least 24 hours have elapsed in a health institution, in any of its services. | through study completion, an average of 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| Time to hospitalization | Number of days elapsed | through study completion, an average of 30 days |
| Percentage of Use of invasive mechanical ventilation support in each arm | All patients who are connected to invasive mechanical ventilation support |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ministry of Public Health of the Province of Corrientes | Corrientes | 3400 | Argentina |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32293834 | Result | Simsek Yavuz S, Unal S. Antiviral treatment of COVID-19. Turk J Med Sci. 2020 Apr 21;50(SI-1):611-619. doi: 10.3906/sag-2004-145. | |
| 18446504 | Result | Gonzalez Canga A, Sahagun Prieto AM, Diez Liebana MJ, Fernandez Martinez N, Sierra Vega M, Garcia Vieitez JJ. The pharmacokinetics and interactions of ivermectin in humans--a mini-review. AAPS J. 2008;10(1):42-6. doi: 10.1208/s12248-007-9000-9. Epub 2008 Jan 25. |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D007559 | Ivermectin |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Placebo | Drug | Patients will receive the tablet from the branch to which they were randomized only at the time of inclusion and 24 hours after the first dose. |
|
| through study completion, an average of 30 days |
| Time to invasive mechanical ventilation support | Number of days elapsed | through study completion, an average of 30 days |
| Percentage of dialysis in each arm | All patients who require temporary or permanent renal replacement therapy | through study completion, an average of 30 days |
| All-cause mortality | Death of the patient, from any cause. | through study completion, an average of 30 days |
| Negative of the swab at 3±1 days and 12±2 days after entering the study | Negative Nasal Swab Using Polymerase Chain Reaction Technique | At days 3±1 and 12±2 |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) | According to the adverse events that patients may present. | through study completion, an average of 30 days |
| 26988202 | Result | Gotz V, Magar L, Dornfeld D, Giese S, Pohlmann A, Hoper D, Kong BW, Jans DA, Beer M, Haller O, Schwemmle M. Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import. Sci Rep. 2016 Mar 18;6:23138. doi: 10.1038/srep23138. |
| 24161512 | Result | Lundberg L, Pinkham C, Baer A, Amaya M, Narayanan A, Wagstaff KM, Jans DA, Kehn-Hall K. Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce Venezuelan Equine Encephalitis Virus replication. Antiviral Res. 2013 Dec;100(3):662-72. doi: 10.1016/j.antiviral.2013.10.004. Epub 2013 Oct 22. |
| 23769930 | Result | Tay MY, Fraser JE, Chan WK, Moreland NJ, Rathore AP, Wang C, Vasudevan SG, Jans DA. Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin. Antiviral Res. 2013 Sep;99(3):301-6. doi: 10.1016/j.antiviral.2013.06.002. Epub 2013 Jun 14. |
| 22417684 | Result | Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012 May 1;443(3):851-6. doi: 10.1042/BJ20120150. |
| 7615630 | Result | Chi NC, Adam EJ, Adam SA. Sequence and characterization of cytoplasmic nuclear protein import factor p97. J Cell Biol. 1995 Jul;130(2):265-74. doi: 10.1083/jcb.130.2.265. |
| 8599106 | Result | Gorlich D, Mattaj IW. Nucleocytoplasmic transport. Science. 1996 Mar 15;271(5255):1513-8. doi: 10.1126/science.271.5255.1513. |
| 16103202 | Result | Rowland RR, Chauhan V, Fang Y, Pekosz A, Kerrigan M, Burton MD. Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in vero cells. J Virol. 2005 Sep;79(17):11507-12. doi: 10.1128/JVI.79.17.11507-11512.2005. |
| 15992957 | Result | Timani KA, Liao Q, Ye L, Zeng Y, Liu J, Zheng Y, Ye L, Yang X, Lingbao K, Gao J, Zhu Y. Nuclear/nucleolar localization properties of C-terminal nucleocapsid protein of SARS coronavirus. Virus Res. 2005 Dec;114(1-2):23-34. doi: 10.1016/j.virusres.2005.05.007. Epub 2005 Jun 29. |
| 32251768 | Result | 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. |
| 34215210 | Derived | Vallejos J, Zoni R, Bangher M, Villamandos S, Bobadilla A, Plano F, Campias C, Chaparro Campias E, Medina MF, Achinelli F, Guglielmone HA, Ojeda J, Farizano Salazar D, Andino G, Kawerin P, Dellamea S, Aquino AC, Flores V, Martemucci CN, Martinez SM, Segovia JE, Reynoso PI, Sosa NC, Robledo ME, Guarrochena JM, Vernengo MM, Ruiz Diaz N, Meza E, Aguirre MG. Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial. BMC Infect Dis. 2021 Jul 2;21(1):635. doi: 10.1186/s12879-021-06348-5. |
| 33234158 | Derived | Vallejos J, Zoni R, Bangher M, Villamandos S, Bobadilla A, Plano F, Campias C, Chaparro Campias E, Achinelli F, Guglielmone HA, Ojeda J, Medina F, Farizano Salazar D, Andino G, Ruiz Diaz NE, Kawerin P, Meza E, Dellamea S, Aquino A, Flores V, Martemucci CN, Vernengo MM, Martinez SM, Segovia JE, Aguirre MG. Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19): a structured summary of a study protocol for a randomized controlled trial. Trials. 2020 Nov 24;21(1):965. doi: 10.1186/s13063-020-04813-1. |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |