Ivermectin Effect on SARS-CoV-2 Replication in Patients With COVID-19
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04381884 |
Recruitment Status :
Completed
First Posted : May 11, 2020
Last Update Posted : October 5, 2020
|
Tracking Information | |||||||
---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | May 5, 2020 | ||||||
First Posted Date ICMJE | May 11, 2020 | ||||||
Last Update Posted Date | October 5, 2020 | ||||||
Actual Study Start Date ICMJE | May 18, 2020 | ||||||
Actual Primary Completion Date | September 29, 2020 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Reduction in SARS-CoV-2 viral load [ Time Frame: 1 - 5 days ] Number of patients in whom the SARS-CoV-2 viral load decreases after Ivermectin treatment
|
||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
|
||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures |
Observed effects to Ivermectin serum concentrations quantified at different treatment time points. [ Time Frame: 1 month ] | ||||||
Original Other Pre-specified Outcome Measures | Same as current | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Ivermectin Effect on SARS-CoV-2 Replication in Patients With COVID-19 | ||||||
Official Title ICMJE | A Pilot, Proof of Concept Trial to Prove Ivermectin Efficacy in the Reduction of SARS-CoV-2 Replication at Early Stages of COVID-19 | ||||||
Brief Summary | In the context of COVID-19 pandemic, a report on ivermectin suppression of SARS-CoV-2 viral replication in cell cultures has been published, and the use of this medication seems to be potentially useful for the therapy. IVM safety profile and IVM wide spectrum enables to move forward with the investigation in patients infected by SARS-CoV-2 as a proof-of-concept of its possible use in the management of patients with COVID-19, given the current pandemic situation. | ||||||
Detailed Description | Ivermectin (IVM) is a semisynthetic antiparasitic agent belonging to the avermectin group, drugs isolated from Streptomyces avermitilis. Ivermectin is widely used for humans and animals, with millions of doses annually administered through mass drug distribution programs held by the World Health Organization (WHO - 2016). Since 1980, Ivermectin has been included in the Essential Medicines List of the World Health Organization (WHO - 2019). This medicine is orally administered and is usually used for the treatment against nematodes and ectoparasites, making this drug the first-choice medication for onchocerciasis, lymph filariasis, itch and strongylosis. Until now, SARS-CoV-2 viral load dynamics has not been clearly determined. However, works tending to a preliminary characterization of the viral load (VL) behavior have emerged. One of them, the most substantial one, includes the work done by Kai-Wang showing the VL behavior during the 30 days before the onset of COVID-19 symptoms (Kai-Wang To et al; 2020). In this work, an average of 7.5 oropharyngeal samples of individuals with severe (n=10) and moderate (n=13) COVID-19 have been assessed. Time between the onset of symptoms and hospitalization ranged between 0 and 13 days, with a mean of 4 days. VL median at day 0 in all patients was 5.2 log10 copies/mL, and no significant differences between severe and moderate COVID-19 groups occurred. The viral load peak observed during the first week from the onset of symptoms had a median equal to 6.91 (Q1-Q3: 4.27-7.40) and 5.29 (Q1-Q3: 3.91-7.56) log10 copies/mL in severe and moderate COVID-19 patients, respectively. There was no significant difference between both groups (p=0.52). Likewise, no difference between patients with and without comorbidities has been observed (n of patients equal to 12 and 11, respectively) as per initial VL (p=0.49) and peak VL (p=0.29). However, it has been observed that the VL peak was directly associated with the age of the patient (R2=0.48 and p=0.02). In a combined analysis of all patients (n=23), it has been observed that the VL grows in the first days following the onset of symptoms and that, in the 5-6 days, VL falls sharply, reaching a lower mean value, yet similar to that of the day 0. General VL behavior from day 9 to 30 showed a negative slope (VL fall) equal to -0.15 (95% confidence interval: -0.19 to -0.11) log10 per daya. It must be emphasized that by day 20 from the onset of symptoms, VL mean continues to be quantifiable (4 log10 copies/mL), and that 7/23 (30%) patients show viral RNA detection after such day. In other paper, the VL of 17 patients with an age median of 59 (range 26-76 years) has been studied, who tested positive for SARS-CoV-2 (Zou et al; 2020). Nonetheless, VL measurement by nasal swab was performed in 16 patients and quantification was conducted relatively, expressed in Ct values (cycle threshold), which is related with the VL copies detected in the molecular reaction: the lower the Ct value, the greater the VL, and vice versa. The feature worth noting of such work is that VL dynamics varies widely from one patient to another. Contrary to the work of Kai-Wang To et al. [1], the VL peak seems to occur earlier (first three days), whereas the sharp VL fall is at day 6 approximately, from which day the VL is undetectable in most patients. Only very few patients show detectable viral RNA after 10 days from the onset of symptoms. In other work, pharyngeal swabs performed in 67 patients have been studied (Pan et al; 2020). VL dynamics similar to that reported by Kai-Wang To et al. is observed, with a VL of approximately 4 to 5 log10 copies/mL at day 0 of the onset of symptoms, a peak at day 6/7 (8 log10 copies/mL) and a sharp fall from day 8 of the onset of symptoms. A temporary onset of viremia is observed with a VL of 4 log10 copies/mL up to day 15 from the onset of symptoms. Finally, in the work published by Wölfel et al. [4] much more accelerated dynamics than that in the work of Kai-Wang To et al. and Pan et al. (Wölfel et al; 2020) is observed, and the peak appearing much earlier than the day 4 from the onset of symptoms in the nine studied patients. Additionally, in 8 patients, the VL falls sharply reaching values below the quantification limit (2 log10 copies/mL) at day 10-11 following the onset of symptoms. Although there are transient VL relapses after day 10, this value remains very close to the study quantification limit. In conclusion, if the works of Kai-Wang and Pan are considered, a greater viral RNA half-life is expected at day 10 following the onset of symptoms. Even though in the works of Zou and Wölfel the peak occurs much earlier than the first five days and viral negativity occurs after day 10-11 following the onset of symptoms. Method variability among the many works is a limiting factor when comparing the outcomes. That is why, due to the sample size in Kai Wang et al (n=23) and Zou et al (n=67), it is suggested to use these works as reference and to consider the works of Pan (n=17) and Wölfel (n=9) as part of behavior diversity. It is important to define the period in which therapy is to be initiated from the onset of symptoms so that the sharp fall observed post-peak is not a factor that biases the potential antiviral effect of the drug. Considering these backgrounds along with the preliminary study with ivermectin, it is not possible to define a specific, progressive outcome for the reduction of the VL, but it may be expressed in a variation percentage with respect to the control population (without therapy) at the end of treatment. This percentage difference between the treated population and the untreated population must be greater than the variation observed for the study day or period in the patients included in the above mentioned works, since such percentage difference would replicate the behavior in our control population. |
||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Patients will be randomized to receive Ivermectin 600 µg / kg / once daily plus standard care or standard care upon diagnosis of COVID-19. Masking: None (Open Label)Primary Purpose: Treatment |
||||||
Condition ICMJE | COVID-19 Drug Treatment | ||||||
Intervention ICMJE | Drug: IVERMECTIN (IVER P®) arm will receive IVM 600 µg / kg once daily plus standard care. CONTROL arm will receive standard care.
IVERMECTIN (IVER P®) arm will receive IVM 600 µg / kg once daily plus standard care. CONTROL arm will receive standard care.
|
||||||
Study Arms ICMJE |
|
||||||
Publications * | Krolewiecki A, Lifschitz A, Moragas M, Travacio M, Valentini R, Alonso DF, Solari R, Tinelli MA, Cimino RO, Alvarez L, Fleitas PE, Ceballos L, Golemba M, Fernandez F, Fernandez de Oliveira D, Astudillo G, Baeck I, Farina J, Cardama GA, Mangano A, Spitzer E, Gold S, Lanusse C. Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial. EClinicalMedicine. 2021 Jun 18;37:100959. doi: 10.1016/j.eclinm.2021.100959. eCollection 2021 Jul. Erratum In: EClinicalMedicine. 2021 Sep;39:101119. | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Completed | ||||||
Actual Enrollment ICMJE |
45 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Actual Study Completion Date ICMJE | September 29, 2020 | ||||||
Actual Primary Completion Date | September 29, 2020 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
|
||||||
Sex/Gender ICMJE |
|
||||||
Ages ICMJE | 18 Years to 69 Years (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | Argentina | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04381884 | ||||||
Other Study ID Numbers ICMJE | IVM-AR-1 | ||||||
Has Data Monitoring Committee | No | ||||||
U.S. FDA-regulated Product |
|
||||||
IPD Sharing Statement ICMJE | Not Provided | ||||||
Current Responsible Party | Laboratorio Elea Phoenix S.A. | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Laboratorio Elea Phoenix S.A. | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE |
|
||||||
Investigators ICMJE | Not Provided | ||||||
PRS Account | Laboratorio Elea Phoenix S.A. | ||||||
Verification Date | October 2020 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |