Ivermectin to Prevent Hospitalizations in COVID-19

Covid19 Clinical Trial

— IVERCORCOVID19  

Official title:

Ivermectin to Prevent Hospitalizations in COVID-19: Randomized, Double-blind, Placebo-controlled

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04529525
• Other study ID #: IVERCORCOVID19MSPICC
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 19, 2020
• Est. completion date: February 22, 2021

Study information

• Verified date: September 2020
• Source: Instituto de Cardiología de Corrientes
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 501
• Est. completion date: February 22, 2021
• Est. primary completion date: February 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Over 18 years of age who reside in the province of Corrientes at the time of diagnosis;

• Confirmed diagnosis of COVID-19 by polymerase chain reaction test for detection of SARS-CoV2 in the last 48 hours;

• In the case of women of childbearing age, they must be using a contraceptive method of proven efficacy and safety (barrier, hormonal or permanent contraceptives) for at least 3 months prior to inclusion in the present study and for the entire period of time for the duration of the study and until at least 30 days after the end of this study. A woman will be considered to have no reproductive capacity if she is postmenopausal (at least 2 years without her menstrual cycles) or if she has undergone surgical sterilization (at least one month before the time of inviting her to participate in this study);

• Weight at the time of inclusion greater than 48,000 kilograms;

• That they sign the informed consent for participation in the study.

Exclusion Criteria:

• Pregnant or breastfeeding women;

• Known allergy to ivermectin or some of the components of ivermectin tablets or placebo;

• Current use of home oxygen;

• That require hospitalization due to COVID-19 at the time of diagnosis or history of hospitalization for COVID-19;

• Presence of mal-absorptive syndrome;

• Presence of any other concomitant acute infectious disease;

• Known history of severe liver disease, for example liver cirrhosis;

• Need or use of antiviral drugs at the time of admission for another viral pathology other than COVID-19;

• Need or use of hydroxychloroquine or chloroquine;

• Use of ivermectin up to 7 days prior to randomization;

• Patients on dialysis or who have required it in the last 2 months or who plan to do it in the next 2 months;

• Current participation or in the last 30 days in a research study that has included the administration of a drug.

Related Conditions & MeSH terms

• Covid19

Intervention

Drug:
• Ivermectin
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.
• Placebo
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.

Locations

Country	Name	City	State
Argentina	Ministry of Public Health of the Province of Corrientes	Corrientes

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Cardiología de Corrientes

Country where clinical trial is conducted

Argentina, 

References & Publications (11)

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. — View Citation

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. — View Citation

González Canga A, Sahagún Prieto AM, Diez Liébana MJ, Fernández Martínez N, Sierra Vega M, García 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 — View Citation

Görlich D, Mattaj IW. Nucleocytoplasmic transport. Science. 1996 Mar 15;271(5255):1513-8. Review. — View Citation

Götz V, Magar L, Dornfeld D, Giese S, Pohlmann A, Höper 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/srep231 — View Citation

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. 2 — View Citation

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 — View Citation

Simsek Yavuz S, Ünal S. Antiviral treatment of COVID-19. Turk J Med Sci. 2020 Apr 21;50(SI-1):611-619. doi: 10.3906/sag-2004-145. Review. — View Citation

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 — View Citation

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. Epub 2005 Jun 29. — View Citation

Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin a/ß-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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Time to hospitalization	Number of days elapsed	through study completion, an average of 30 days
Secondary	Percentage of Use of invasive mechanical ventilation support in each arm	All patients who are connected to invasive mechanical ventilation support	through study completion, an average of 30 days
Secondary	Time to invasive mechanical ventilation support	Number of days elapsed	through study completion, an average of 30 days
Secondary	Percentage of dialysis in each arm	All patients who require temporary or permanent renal replacement therapy	through study completion, an average of 30 days
Secondary	All-cause mortality	Death of the patient, from any cause.	through study completion, an average of 30 days
Secondary	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
Secondary	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