Clinical trial NCT04646109
Conditions: COVID-19
Keywords: Ivermectin SARS-CoV-2 Treatment
Sponsor: Afyonkarahisar Health Sciences University
Start date: 2020-05-11; Completion date: 2020-09-02
Enrollment: 66 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
In this multicenter study; it was aimed to investigate the effectiveness and safety of ivermectin use in the treatment of patients with severe COVID-19 pneumonia that have no mutations which alter ivermectin metabolism and cause side effects.

Detailed description:
Patients with severe COVID-19 pneumonia were included in the study. Two groups, the study group and the control group, took part in the study.

Ivermectin 200 mcg/kg/day for five days (9 mg between 36-50 kg, 12 mg between 51-65 kg, 15 mg between 66-79 kg and 200 microgram/kg in \> 80 kg) in the form of a solution prepared for enteral use added to the reference treatment protocol -hydroxychloroquine (2x400mg loading dose followed by 2x200mg, po, 5 days) + favipiravir (2x1600mg loading dose followed by 2x600mg maintenance dose, po, total 5 days) + azithromycin (first day 500mg followed by 4 days 250mg/day, po, total 5 days)- of patients included in the study group. Patients in the control group were given only reference treatment with 3 other drugs without ivermectin.

The mutations in 29 pairs of primers in mdr1/abcab1 gene by sequencing analysis using Sanger method, and the haplotypes and mutations of the CYP3A4 gene that cause the function losing were investigated among the patients who meet criteria and who were included in the study group according to randomization. Mutation screening was done when the first dose of the research drug ivermectin was given, ivermectin treatment was not continued in patients with mutations detected as a result of genetic examination and these patients were excluded from the study.

Patients were followed for 5 additional days after treatment. At the end of the treatment and follow-up period (At the end of 10th day), clinical response and changes in oxygenation and laboratory parameters were evaluated.

Arms: arm 1: Patients who were hospitalised with a pre-diagnosis of severe COVID-19 pneumonia and thereafter diagnosis of COVID-19 was also confirmed microbiologically with PCR positivity in respiratory tract samples were included into the study. They were randomized to the control and study group, respectively. Hydroxychloroquine, favipiravir and azithromycin (HFA) standard treatment protocol were given to the control group as recommended in the "COVID-19 (SARS-CoV-2 Infection) Guide" prepared by the Republic of Turkey Ministry of Health. arm 2: In addition to HFA treatment, ivermectin 200 micrograms/kg/day (9mg between 36-50 kg, 12mg between 51-65 kg, 15mg between 66-79 kg and 200 micrograms/kg in \> 80 kg) in the form of a solution prepared for enteral use was added (HFA+I) to the treatment protocol of the study group's for five days. Blood sample was taken with the first dose of ivermectin and haplotype analysis was performed in ABCB1 and CYP3A4 genes in the whole study group.
Interventions: intervention 1: Ivermectin
Intervention descriptions: intervention 1: Ivermectin 5mg/5ml solution was manufactured by NEUTEC™ Pharmaceutical Company-Turkey, under "Good Manufacturing Practices" (GMP) certification conditions.

Protocol documents:
SAP_002.pdf: 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
Study name: Evaluation Of The Effectiveness And Safety Of Adding Ivermectin to 
Treatment in Severe COVID-19 Patients 
Study protocol cod: IVMC_03 
Ethics committee approval number and date: 139/03.04.2020 
Coordinator researcher: Prof. Dr. Nurullah OKUMUŞ 
 
 
 
 
 
 
 
 
 
 
 
Date: 04.05.2020 Version: 3 


 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
Convenience Sampling method will be used in the study. Unilateral blinding will be 
made in determining which of the study and control groups participating patients will be 
included in the study, those with an odd number will be included in the study group, and 
those with an even number will be included in the control group. 
 
In determining the sample size, it was planned to include 30 individuals in each group 
based on the number of available kits. In this case, the values of 0.05 for Type I Error 
Rate, 0.67 for Effect Size and 0.80 for Power were reached. 
 
The Chi-Square test will be used in the evaluation of categorical data, the Wilcoxon test 
for in-group comparisons, and the Mann-Whitney U test for intergroup comparisons. For 
statistical significance, the value of p=0.05 will be taken into account and the analyzes 
will be carried out in the SPSS 20.0 package program. 
 
Date: 04.05.2020 Version: 3 

ICF_001.pdf: 
1-5 
 
 
 
INFORMED CONSENT FORM 
 
Name of Research Project: Evaluation of the Effectiveness and Safety of Adding Ivermectin to 
Treatment in Severe COVID19 Patients 
Name of Coordinator Researcher: Prof. Dr. Nurullah OKUMUŞ 
 
Dear Volunteer, 
We invite you to be a volunteer in a voluntary study in which the efficacy and safety of the drug called 
ivermectin is evaluated. 
This study is for research purposes. It has no profit aim in any way. 
Clinical COVID19 disease caused by the new corona virus (SARS CoV-2) progresses from mild, self-
limiting mild respiratory disease to severe pneumonia, multi-organ failure and death. The disease can 
be fatal in patients with severe prognosis, and currently used treatments may not provide full 
effectiveness in every patient. 
Currently, the standard treatment recommended by the Ministry of Health in our country is used in all 
patients with severe COVID19 disease. In our research, in addition to this treatment, we will use 
ivermectin drug, which was previously used in parasites and some viral diseases in humans and has been 
shown to be effective against SARS CoV-2 virus in a new study. We think that ivermectin may also be 
effective in COVID19 patients and will help recovery in patients with severe prognosis. 
A total of 60 (sixty) patients who were diagnosed with severe COVID19 disease and are> 18 years old 
will be included in the study. If you agree to volunteer in the study, the prescribed time for receiving 
treatment is 5 days. Participation in the study is entirely at your discretion, and you can withdraw from 
the study at any time. Your information recorded for the study will not be used elsewhere in any way. 
In this study; Patients presenting with severe COVID19 infection clinical status will be given odd and 
even numbers in order of application. Odd numbers will be grouped as "study group" and even numbers 
as "control group".  
Date: 04.05.2020 Version: 3 


2-5 
 
If you are in the control group, you will receive Hydroxychloroquine (2x400 mg loading dose followed 
by 2x200 mg orally for a total of 5 days) ± Favipiravir (2x1600 mg loading dose followed by 2x600 mg, 
orally for a total of 5 days) ± Azithromycin (500mg on the first day followed by 250mg / day by mouth 
for a total of 5 days) treatment which is currently used in our country and recommended by the Scientific 
Committee of the Ministry of Health.  
If you are in the study group, in addition to this treatment; Ivermectin, which we evaluated in our study, 
is suitable for oral use at a dose of 200 mcg/kg/day (9 mg between 36-50 kg, 12 mg between 51-65 kg, 
15 mg between 66-79 kg,> 80 kg 200 mcg / kg) will be given to you orally or with the help of a catheter 
for five days in the form of a prepared solution . 
The most common side effects during ivermectin treatment are fever, headache, dizziness, itching and 
rash. Skin reactions and asthma can be worsen. Rarely, neurological side effects such as encephalopathy, 
confusion and coma have been reported during the use of ivermectin. In our study, side effects will be 
monitored closely in all patients taking this drug, and if any side effects are observed, your treatment 
will be terminated. You volunteers who will participate in the study will also be informed about the side 
effects of drugs such as hydroxychloroquine, azithromycin and favipiravir in the reference treatment. 
Some side effects can be seen in people with some genetic differences during the use of ivermectin. In 
our study, volunteers who will receive ivermectin will first be tested for these genetic differences (MDR-
1 / ABCB1 and CYP3A4 mutations). It is entirely up to you whether to participate in this genetic study 
and the subsequent ivermectin efficacy and safety study. In people with these genetic differences, 
ivermectin metabolism may be disrupted and harmful effects of ivermectin may occur. If you are in the 
patient group to be given ivermectin and if these gene mutations are detected by genetic study, you 
will be excluded from the study due to the possibility of side effects. 
Blood samples to be taken for genetic studies will be studied in the laboratories of Intergen company. 
After the study is completed, without your consent, the samples taken from you will be duly destroyed 
at the current center, in accordance with the law. The storage of the blood sample taken by you and its 
use in further studies are only subject to your consent. These examples can be stored for many years, 
provided that your name (identity information) is protected or destroyed.  
If you allow to be taken your blood sample for genetic study, please sign only one of the options in the 
boxes below that is suitable for you. 


3-5 
 
 
ӿ Coded sample: The sample taken from you is given a code number. Only the researcher knows the code 
number and only the researcher can access your identification information. Thus, your credentials are kept 
confidential. 
 
 
 
 
 
I approve the use of the ӿ coded blood sample taken by me only for this study investigating the efficacy 
and safety of Ivermectin use in COVID19 infection; I do not give consent for future studies related to 
possible COVID19 infection. 
Name-Surname (by handwriting):                               
 
Signature: 
I approve the use of the coded blood sample taken by me only for this study investigating the efficacy 
and safety of Ivermectin use in COVID19 infection; I would like to be informed again and give new 
approval for future studies related to possible COVID19 infection. 
Name-Surname (by handwriting):                               
 
Signature: 
 
I approve the use of the coded blood sample taken by me in other studies related to COVID19 infection, 
but I would like to be informed again and give new approval in other studies (including genetic studies) 
other than COVID19 infection. 
Name-Surname (by handwriting):                               
 
Signature: 
 


4-5 
 
If you agree to voluntarily participate in this study; You have responsibilities such as cooperating with 
the researchers who conducted the study, providing accurate information (about your accompanying 
additional health problem, drug allergy, medications you are constantly using, etc.), your clinical 
situation, the treatment and methods applied, and not reporting the information about the results of 
the study to third parties. 
If you agree to voluntarily participate in this study; Records that will reveal your identity will be kept 
confidential, will not be disclosed to the public, and your identity will be kept confidential even if the 
research results are published. In addition, the study monitors, reviewers, ethics committee and other 
relevant health authorities will have direct access to your original medical records, but this information 
will be kept confidential. By signing the written informed consent form, you or your legal representative 
will allow such access. You or your legal representative will be notified in a timely manner as soon as 
new information regarding the research topic becomes available that will affect your willingness to 
continue participating in the research. 
If you agree to participate in the study, no payment will be made to you. However, against the possibility 
of any harm caused by the work, your health insurance will be taken out to compensate the damage and 
to make any necessary medical intervention. 
Whether or not to take part in this study is entirely up to you. If you decide to participate this will be 
given to you to sign the written informed consent form. If you are unable to give consent or sign, consent 
and signature will be obtained from the person who is your legal representative. 
Even if you sign this form right now, you are free to stop working at any time without giving a reason. If 
you make such a decision, your medical care will not be affected in any way. 
 
----------------------------------------------------------------------------------------------------------------- 
 
 
 
 
 
 
 
 
 
 
 
 


5-5 
 
----------------------------------------------------------------------------------------------------------------- 
 
I have read (or listened to) the above text, which contains the information that should be given to 
the volunteers before starting the research. I asked the researchers my questions on issues I 
thought were missing and got satisfactory answers. I am of the opinion that I understood all the 
written and oral statements submitted to me in detail. Ample time was given to decide whether I 
would like to participate in the study. 
 
When I encounter a health problem during research; I know that I can reach the responsible 
researchers whose names and phone numbers are given below at any time. 
 
Responsible researchers; Prof. Dr. Neşe DEMİRTÜRK (Phone: 0505 4775515), Ass. Prof. Dr. Rıza Aytaç 
ÇETİNKAYA (Phone: 0505 4382814), Prof. Dr. İsmail Yaşar Avcı (Phone: 0532 2927212, 0533 6689733) 
 
Under these circumstances, I declare that I voluntarily accept to participate in the study titled 
“Evaluation of the Effectiveness and Safety of Adding Ivermectin to Treatment in Patients with 
Severe Course of COVID19”, without any pressure or coercion, provided that confidentiality rules 
are observed. 
 
The volunteer:  
 
 
 
 
Legal representative:   
Name, surname:                                                             
Name, surname:                                                                     
Date:   
 
 
 
 
 
Date:   
 
 
Signature:  
 
 
 
 
 
Signature:  
 
The researcher making the information: 
Name, surname: 
Date: 
Signature: 
 
----------------------------------------------------------------------------------------------------------------- 

Prot_000.pdf: 
1 
 
 
 
STUDY PROTOCOL 
 
Introduction and Aim 
 
Since the first case was reported in Wuhan, China in December 2019, the SARS CoV-
2-induced COVID19 epidemic, which has surrounded the whole world with great 
speed, still continues its effect as a pandemic. According to the first reports, SARS 
CoV-2, which was reported to originate from the live animal market in Wuhan and 
has been associated with two bat corona viruses so far, has also gained the ability to 
be transmitted from person to person and spread all over the world. SARS CoV-2 is 
an enveloped, single-stranded betacoronavirus. The virus is mainly found in the 
respiratory secretions of patients and it is transmitted to susceptible people by 
droplets as a result of the spillage of these secretions into the environment. However, 
to date, it has been shown that the virus is also found in the gastrointestinal canal, 
feces and urine, and it has been reported that it is necessary to investigate whether it 
is transmitted by these means (1,2). 
 
In a meta-analysis that evaluated nine studies and included a total of 50,404 patients, 
the main symptoms seen in COVID19 were reported as high fever, cough, myalgia 
and fatigue. In the same publication, a severe picture with acute respiratory failure is 
defined in 14.8% of the patients, and the average mortality is reported as 4.8% (3). In 
the diagnosis of the disease, lung tomography findings, which are compatible with 
the clinic, are particularly important (4). 
 
EVALUATION OF THE EFFECTIVENESS AND SAFETY OF ADDING 
IVERMECTIN TO TREATMENT IN SEVERE COVID-19 PATIENTS 
Date: 04.05.2020 Version: 4 


2 
 
The gold standard for microbiological diagnosis of the disease is to search for virus 
RNA in respiratory tract samples by real-time PCR. However, these tests are likely to 
give false negative results. In this case, radiological findings and some hematological 
parameters are used for diagnosis. It has been reported that most of the patients 
have lymphopenia, high CRP and d-dimer levels, and procalcitonin levels are close to 
normal. For faster diagnosis, rapid diagnostic tests have been developed to detect 
IgM / IgG type antibodies in blood samples of patients, and there are studies 
conducted to determine the sensitivity and specificity of these tests (1,3). 
 
There is no drug with proven efficacy in the treatment of the disease. Ribavirin, 
hydroxychloroquine, lopinavir-ritonavir, remdesivir, favipiravir, azithromycin are 
among the drugs being tried. In patients with severe prognosis and with septic shock, 
cytokine antagonists such as corticosteroids, tocilizumab, and plasma treatments 
obtained in recovered patients are tried (5,6). 
 
Ivermectin, which is an antiparasitic drug effective against endo and ecto parasites in 
the structure of 22,23 dihydroavermectin B1, which is produced semi-synthetically 
from the avermectin family, has been approved by the FDA for oral use in humans, it 
is a highly effective drug for ascariasis, cutaneous larval migrans, strongiloidosis, 
onchocerciasis, and scabies (7). 
 
In addition to its antiparasitic activity, ivermectin has been shown in in vitro studies in 
recent years that it has antiviral efficacy against many viruses such as human 
immunodeficiency virus (HIV-1), dengue virus and western nile virus. In a phase 3 
study between 2014 and 2017 in people with Deng virus infection in Thailand, it was 
reported that orally once a day was used and it was safe, and it did not provide 
clinical improvement, although a significant decrease was observed in the serum viral 
NS1 protein level (8, 9). 


3 
 
The most common side effects during ivermectin treatment; fever, headache, 
dizziness, itching and rash. Rarely, neurological side effects such as encephalopathy, 
confusion and coma have been reported during the use of ivermectin in the 
treatment of onchoceriosis. These side effects have been shown in animal and human 
studies to be related to the mdr-1 gene mutation. It has been shown that in persons 
carrying the SNP (single nucleotide polymorphisms) mutation in the mdr-1 / abcb1 
gene encoding P-glycoprotein, this gene expression decreases and ivermectin passes 
to the central nervous system and accumulates and leads to encephalopathy. 
 
In addition, it has been reported that haplotypes and mutations in the CYP3A4 Gene 
that give and lose function cause toxic effects or drug dosing by changing the 
metabolic rate of ivermectin. 
 
In a recently published in vitro study from Australia, the efficacy of ivermectin used as 
an antiparasitic agent on SARS-CoV-2 was evaluated and Vero/hSLAM cells were 
infected with this virus in vitro and exposed to ivermectin, after 48 hours there was a 
99.8% reduction in viral load. Based on these studies, it can be thought that 
ivermectin, which has also been shown to have antiviral efficacy in different studies, 
may also be effective in COVID19 patients (8). 
 
In this study, it is aimed to evaluate the effect of ivermectin addition to the 
"Hydroxychloroquine ± Favipiravir ± Azithromycin" combination therapy, which is the 
reference treatment recommended in the "Covid19 Guideline" prepared by the 
Ministry of Health, on clinical response in patients with severe COVID19 pneumonia 
and to investigate the safety of ivermectin use in these patients (10). 
 
 
 
 


4 
 
Material and Method 
 
The study will be conducted as a prospective, randomized, controlled, single-blind 
Phase 3 study. Patients with severe COVID19 disease who were hospitalized in 
Afyonkarahisar Health Sciences University, Health Sciences University Istanbul Sultan 
Abdülhamid Han Training and Research Hospital, Ankara City Hospital and Health 
Sciences University Ankara Gülhane Training and Research Hospital COVID19 service 
and intensive care units will be included in the study.  
 
There will be two patient groups in the study, the study arm and the control arm. A 
total of 60 patients, including 30 in both arms, are planned to be included in the 
study. 
 
Patient Selection and Inclusion Criteria 
 
Patients who were hospitalized with a pre-diagnosis of *severe COVID-19 pneumonia 
and thereafter diagnosis of COVID-19 was also confirmed microbiologically with PCR 
positivity in respiratory tract samples were included into the study (13). They were 
randomized to the study and control group, respectively. 
* Patients with at least one of the criteria below were accepted as patients with severe 
COVID-19 pneumonia; 
a. Presence of tachypnea ≥30/minute, SpO2 level <90% in room air, PaO2/FiO2 <300 
in oxygen receiving patient 
b. Presence of specific radiological finding for Covid-19 in lung tomography (bilateral 
lobular, peripherally located, diffuse patchy ground glass opacities) 
c. Mechanical ventilation requirement 
d. Acute organ dysfunction findings; patients with SOFA (sepsis-related organ failure 
assessment) score> 2 


5 
 
 
  
 
Mutations in the mdr1 / abcab1 gene and the CYP3A4 gene will be investigated in 
patients who meet any of the above criteria and are> 18 years of age and enrolled in 
the study group by randomization. Patients with mutations will not be included in the 
study. 
 
Exclusion Criteria 
Patients with the following characteristics were excluded from the study. 
1. Pediatric patients; <18 years of old 
2. Patients with chronic liver or kidney disease 
3.Pregnant women 
4. Patients with known ivermectin allergy 
 
 
 
 


6 
 
 
Genetic study  
 
In the patients included in the study group, the mutation in 29 pairs of primers and the 
haplotypes and mutations of the CYP3A4 gene will be investigated by performing 
sequence analysis in the mdr1 / abcab1 gene with the Sanger method. 
 
Design of Primers 
"PRIMER © – Primer Designer v.2.0 (Scientific & Educational Software)" software will 
be used in primer design for mutation research. Primers will be synthesized by 
Metabion International AG. Sequence analysis plan and primer design will be made, 
including the coding regions of these genes, exon-intron junction regions. 
 
Sanger Sequence Analysis 
DNA fragments for all patients will be sequenced with the ABI 3130 sequence 
analyzer after amplification using polymerase chain reaction (PCR) followed by bi-
directional fluorescent markers using BigDye chemistry (Life Technologies, Carlsbad, 
CA, USA). The sequences will be read with the Seqscape program. Variants obtained 
here will be analyzed according to ACMG criteria and variants will be classified. In the 
analysis of variants, data will also be evaluated using relevant databases to identify 
known haplotypes. 
 
 
 
 
 
 


7 
 
Treatment and patient follow-up 
 
The following reference treatment recommended by the Ministry of Health will be 
applied to all patients in the control and study groups; 
1. Hydroxychloroquine (2x400mg loading dose followed by 2x200mg, po, 5 days) 
2. Favipiravir (2x1600mg loading followed by 2x600mg, po, maintenance dose for a 
total of 5 days) 
3.Azithromycin (500mg first day followed by 250mg / day 4 days, po, 5 days total) 
 
In addition to the reference therapy, ivermectin at a dose of 200 mcg / kg / day (9 mg 
between 36-50 kg, 12 mg between 51-65 kg, 15 mg between 66-79 kg,> 80 kg 
200mcg / kg) It will be applied for five days in the form of a solution prepared for 
enteral use (Ivermectin 5mg/5ml solution was manufactured by Neutec 
Pharmaceutical-Turkey, under GMP conditions). 
 
Patients in the control arm will be given reference treatment with the other 3 drugs 
without giving ivermectin. 
 
The drug whose effectiveness will be evaluated in the study is ivermectin. Ivermectin 
is an FDA-approved antiparasitic drug. Approved adult dose in parasitic infections is 
reported as 200mcg / kg / day (11). Although ivermectin has been shown to be 
effective in SARS CoV-2 in vitro, there is no randomized prospective controlled study 
showing that it is effective in COVID19 patients. In a very recent study that is still in 
press, it has been reported that it significantly reduces mortality in COVID19 patients, 
and in this study, no information is given about the duration and dosage of use (12). 


8 
 
In a study conducted in Thailand on the use of ivermectin in dengue fever infection, it 
was reported that it was used at doses of 200mcg / kg / day and 400mcg / kg / day 
(13). 
 
Ivermectin antiparasitically as a single daily or multi-dose intermittent sequential; In 
dengue fever infection, considering the use of 200 or 400 mcg / kg / day as an antiviral 
for 3 days, it is seen that the total dose given in antiviral treatment reaches up to 1200 
mcg / kg / day (14,15,16). Based on all these studies, we planned to use ivermectin at 
a dose of 200 mcg / kg / day, which is approved by the FDA, in our study. Definitive 
recommendations for treating COVID19 disease Although not, the duration of 
treatment with antiviral drugs is recommended as 5 days in the guide prepared by the 
Scientific Committee of the Ministry of Health. Considering that the average duration 
of symptoms in patients is 5-7, the duration of ivermectin treatment was planned as 5 
days in our study, and it was planned to reach a total dose of 1000 mcg / kg / day, 
close to the total dose used in viral infections in the literature. The treatment can be 
terminated in less than 5 days if the patients reach the treatment early or if there are 
side or toxic effects. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


9 
 
Study Design 
 
In all patients included in the study; demographic data, comorbid conditions, 
admission symptoms, complete blood count and biochemical blood examinations at 
the time of admission, initial SARSCoV-2 PCR results and thoracic tomography findings 
at presentation will be recorded. 
 
During the study; respiratory findings and laboratory parameters of the patients will be 
recorded on the 1st, 3rd and 5th days of the treatment and on the 1st, 3rd and 5th 
days after the treatment, during the follow-up period. Side effects observed during the 
treatment in all patients also will be recorded. 
 
Primary and secondary endpoints for efficacy and safety assessment in the study will 
be determined as follows: 
 
Primary endpoint: Clinical responses and drug side effects obtained in patients on the 
5th day, at the end of the ivermectin treatment will be evaluated. Extubation in 
mechanically ventilated patients, respiratory rate <26, SpO2 level in room air > 90%, 
PaO2 / FiO2> 300 in patients receiving oxygen, presence of at least two of the 2-point 
reduction criteria in SOFA score will be evaluated as "clinical response".  
 
Secondary endpoint: Clinical responses and drug side effects obtained in patients on 
the 5th day after the end of ivermectin treatment will be evaluated. For clinical 
response, the presence of at least two of the following criteria is sought: Respiration 
rate between 22-24, SpO2 level in room air >95%, absence of oxygen requirement, 
observation of radiological improvement in control lung tomography, no need for 
intensive care.  
 


10 
 
In order to evaluate the treatment response in patients; blood lymphocyte count, CRP, 
ferritin and d-dimer values, changes in polymorphonuclear leukocyte/lymphocyte 
(PNL/L) ratio, changes in SpO2 and PaO2/FiO2 ratio will be determined and compared 
between both groups. Mortality rates at the end of the follow-up period will be also 
evaluated in both groups. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


11 
 
REFERENCES 
1. 
Guan WJ, Ni ZY, Hu Y et al. Clinical Characteristics of Corona virüs Disease  2019 in China. N Engl J Med. 
2020 Feb 28. doi: 10.1056/NEJMoa2002032. [Epub ahead of print].   
2. 
Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-
2) and corona virus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimic Agent 2020; 
doi.org/10.1016/j.ijantimicag.2020.105924 
3. 
Li Z , Yi Y, Luo X et al. Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test 
for SARS-CoV-2 Infection Diagnosis. J Med Virol 2020;doi: 10.1002/jmv.25727. [Epub ahead of print].  
4. 
CaoY, Liu X, Xiong L, Cai K. Imaging and Clinical Features of Patients With 2019 Novel Corona virus SARS-
CoV-2: A systematic review and meta-analysis. J med Virol 2020; doi: 10.1002/jmv.25822. [Epub ahead of 
print] 
5. 
Shen C, Wang Z, Zhao F et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. 
JAMA 2020; doi:10.1001/jama.2020.4783 
6. 
Wang M, Cao R, Zhang L et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel 
coronavirus (2019-nCoV) in vitro. Cell Res 2020;doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4. 
7. 
Croci R, Bottaro E, Chan KWK et al. Liposomail systems as nanocarriers for the antiviral agent İvermektin. 
Int J Biomater 2016:8043983. doi: 10.1155/2016/8043983. 
8. 
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The-FDA approved drug ivermektin inhibits the 
replication of SARSCoV-2 in vitro. Antivir Res 2020; https://doi.org/10.1016/j.antiviral.2020.104787 
9. 
Mastrangelo E, Pezzullo M, Burghgraeve TD et al. Ivermecyin is a potent inhibitor of flavivirus replication 
specifically targeting NS3 helicase activity: new prospects for an old drug. J Antimicrob Chemother 
2012;67:1884-1894.  
10. https://covid19bilgi.saglik.gov.tr/depo/rehberler/COVID-19_Rehberi.pdf 
11. https://www.sanfordguide.com/products/digital-subscriptions/sanford-guide-to-antimicrobial-therapy-
mobile/ 
12. Patel AN, Desai SS, Grainger DW, Mehra MR. Usefullness of ivermectin in COVID19 illness. (April 19, 2020). 
Available at SSRN: https://ssrn.com/abstract=3580524 
13. https://clinicaltrials.gov/ct2/show/study/NCT02045069 
14. Torres JR, Isturiz R, Murillo J, Guzman M, Contreras R. Efficacy of Ivermectin in the Treatment of 
Strongyloidiasis Complicating AIDS. Clın Infect Dis 1993;17:900-902.  
15. Yamasmith E, Avirutnan P, Mairiang D et al. Efficacy and safety of ivermectin against Dengue infection: a 
phase III,randomised, double-blind, placebo-controlled trial. The 34th Annual Meeting The Royal College 
of Physicians of Thailand 'Internal Medicine and One Health' 26th - 28th April 2018, PEACH Royal Cliff 
Beach Resort, Pattaya, Chonburi, Thailand 
16. Avirutnan P, Mairiand D.  Pharmacokinetics and pharmacodynamics of ivermectin in pediatric dengue 
patients (PKIDEN).  https://clinicaltrials.gov/ct2/show/NCT03432442