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

Covid19 Clinical Trial

— SAINTBO  

Official title:

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).

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04836299
• Other study ID #: RCT01
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 8, 2021
• Est. completion date: December 5, 2021

Study information

• Verified date: April 2021
• Source: Universidad Mayor de San Simón
• Contact: Jorge L Aviles, MPH
• Phone: +59170745106
• Email: georgeavi[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

1. To evaluate the efficacy of ivermectin in reducing the SARS-CoV-2 viral load in the nasopharyngeal swab on day 7 after treatment.

2. To evaluate the efficacy of ivermectin in improving the progression of symptoms in treated patients.

3. Assess the proportion of seroconversions in patients treated on day 21.

4. Evaluate the safety of ivermectin at the proposed dose.

5. Determine the magnitude of the immune response against SARS-CoV-2

6. Evaluate the early kinetics of immunity against SARS-CoV-2

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: December 5, 2021
• Est. primary completion date: July 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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:

1. Known history of ivermectin allergy

2. Hypersensitivity to any component of ivermectin or the excipients of the brand to be used.

3. COVID-19 pneumonia

• Diagnosed by the treating physician

• Identified on a chest x-ray

4. Fever or cough present for more than 48 hours.

5. 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.

Related Conditions & MeSH terms

• Covid19

Intervention

Drug:
• Ivermectin
Participants will be randomly assigned to receive a single 600 µg / kg dose of ivermectin or placebo.
• Placebo
Participants will be randomly assigned to receive a single of placebo.

Locations

Country	Name	City	State
Bolivia	Universidad Mayor de San Simón	Cochabamba

Sponsors (3)

Lead Sponsor	Collaborator
Universidad Mayor de San Simón	Barcelona Institute for Global Health, Université Catholique de Louvain

Country where clinical trial is conducted

Bolivia, 

References & Publications (19)

Alout H, Foy BD. Ivermectin: a complimentary weapon against the spread of malaria? Expert Rev Anti Infect Ther. 2017 Mar;15(3):231-240. doi: 10.1080/14787210.2017.1271713. Epub 2016 Dec 29. Review. — View Citation

Aroke D, Tchouakam DN, Awungia AT, Mapoh SY, Ngassa SN, Kadia BM. Ivermectin induced Steven-Johnsons syndrome: case report. BMC Res Notes. 2017 May 8;10(1):179. doi: 10.1186/s13104-017-2500-5. — View Citation

Badhan R, Zakaria Z, Olafuyi O. The Repurposing of Ivermectin for Malaria: A Prospective Pharmacokinetics-Based Virtual Clinical Trials Assessment of Dosing Regimen Options. J Pharm Sci. 2018 Aug;107(8):2236-2250. doi: 10.1016/j.xphs.2018.03.026. Epub 2018 Apr 5. — View Citation

Bray M, Rayner C, Noël F, Jans D, Wagstaff K. Ivermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses. Antiviral Res. 2020 Jun;178:104805. doi: 10.1016/j.antiviral.2020.104805. Epub 2020 Apr 21. — View Citation

Chaccour C, Hammann F, Ramón-García S, Rabinovich NR. Ivermectin and COVID-19: Keeping Rigor in Times of Urgency. Am J Trop Med Hyg. 2020 Jun;102(6):1156-1157. doi: 10.4269/ajtmh.20-0271. — View Citation

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30. — View Citation

Chosidow A, Gendrel D. [Safety of oral ivermectin in children]. Arch Pediatr. 2016 Feb;23(2):204-9. doi: 10.1016/j.arcped.2015.11.002. Epub 2015 Dec 14. Review. French. — View Citation

Choudhary R, Sharma AK. Potential use of hydroxychloroquine, ivermectin and azithromycin drugs in fighting COVID-19: trends, scope and relevance. New Microbes New Infect. 2020 Apr 22;35:100684. doi: 10.1016/j.nmni.2020.100684. eCollection 2020 May. Review. — View Citation

Foletto VR, Vanz F, Gazarini L, Stern CA, Tonussi CR. Efficacy and security of ivermectin given orally to rats naturally infected with Syphacia spp., Giardia spp. and Hymenolepis nana. Lab Anim. 2015 Jul;49(3):196-200. doi: 10.1177/0023677214562850. Epub 2014 Dec 5. — View Citation

Guzzo CA, Furtek CI, Porras AG, Chen C, Tipping R, Clineschmidt CM, Sciberras DG, Hsieh JY, Lasseter KC. Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. J Clin Pharmacol. 2002 Oct;42(10):1122-33. — View Citation

Heidary F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. J Antibiot (Tokyo). 2020 Sep;73(9):593-602. doi: 10.1038/s41429-020-0336-z. Epub 2020 Jun 12. — View Citation

Patrì A, Fabbrocini G. Hydroxychloroquine and ivermectin: A synergistic combination for COVID-19 chemoprophylaxis and treatment? J Am Acad Dermatol. 2020 Jun;82(6):e221. doi: 10.1016/j.jaad.2020.04.017. Epub 2020 Apr 10. — View Citation

Rizzo E. Ivermectin, antiviral properties and COVID-19: a possible new mechanism of action. Naunyn Schmiedebergs Arch Pharmacol. 2020 Jul;393(7):1153-1156. doi: 10.1007/s00210-020-01902-5. Epub 2020 May 27. — View Citation

Schmith VD, Zhou JJ, Lohmer LRL. The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19. Clin Pharmacol Ther. 2020 Oct;108(4):762-765. doi: 10.1002/cpt.1889. Epub 2020 Jun 7. — View Citation

Sharun K, Dhama K, Patel SK, Pathak M, Tiwari R, Singh BR, Sah R, Bonilla-Aldana DK, Rodriguez-Morales AJ, Leblebicioglu H. Ivermectin, a new candidate therapeutic against SARS-CoV-2/COVID-19. Ann Clin Microbiol Antimicrob. 2020 May 30;19(1):23. doi: 10.1186/s12941-020-00368-w. — 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

The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro https://doi.org/10.1016/j.antiviral.2020.104787. https://covid19-evidence.paho.org/handle/20.500.12663/988?locale-attribute=es

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum in: JAMA. 2021 Mar 16;325(11):1113. — View Citation

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Need for supplemental oxygen	The need for supplemental oxygen implementation will be evaluated	28 days
Other	Hospital stay	The need for hospital care and the stay both in general wards and in intensive care (ICU) will be evaluated.	3 months
Other	Need for mechanical ventilation	The need to implement the intervention through mechanical ventilation will be evaluated.	21 days
Primary	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
Primary	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	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

External Links

•   SARS-CoV-2 Ivermectin Navarra-ISGlobal Trial (SAINT)