Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| NeuTec Pharma | INDUSTRY |
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control Group | No Intervention | 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. | |
| Study Group | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ivermectin | Drug | Ivermectin 5mg/5ml solution was manufactured by NEUTEC™ Pharmaceutical Company-Turkey, under "Good Manufacturing Practices" (GMP) certification conditions. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Gender Distribution of the Patients | The gender of patients (Male/female) in both groups were recorded at the time of inclusion. | At the first day of the study |
| Age Distribution of the Patients | The age of the patients (years) in both groups were recorded at the time of inclusion. | At the first day of the study |
| Percentage of Patients With Accompanying Diseases | At the beginning of the study, the patients were asked whether there were any of the following accompanying diseases and the percentage of patients with accompanying disease in both groups were recorded:
| At the first day of the study |
| Percentage of Patients With Baseline Clinical Symptoms | At the beginning of the study, the patients were asked whether there were any of the following clinical symptoms and the percentage of patients with any of the clinical symptoms in both groups were recorded:
| At the first day of the study |
| Body Temperature Means of the Patients | At the beginning of the study, the body temperatures (as degree celcius) of the patients were measured and the mean body temperature values of both groups were recorded. | At the first day of the study |
| Heart Rate Means of the Patients | At the beginning of the study, the heart rates (as per minute) of the patients were measured and the mean heart rate values of both groups were recorded. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Clinical Response | The presence of at least two of the following criteria in patients on the 10th day were accepted as "clinical response": Respiration rate between 22-24/min, SpO2 level in room air >95%, absence of oxygen requirement, observation of radiological improvement in control lung tomography and no need for intensive care. | 10 days (5 days ivermectin therapy plus 5 days follow-up) |
Not provided
Inclusion Criteria:
Patients with at least one of the criteria below were accepted as patients with severe COVID-19 pneumonia;
Exclusion Criteria:
Patients with the following characteristics were excluded from the study.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Nurullah Okumuş, Prof. Dr. | Afyonkarahisar Health Science University, Afyonkarahisar, Turkey | Study Chair |
| Neşe Demirtürk, A. Prof. Dr. | Afyonkarahisar Health Science University, Afyonkarahisar, Turkey | Study Director |
| Rıza A. Çetinkaya, Prof. Dr. | Haydarpasa Sultan Abdulhamid Han Training and Research Hospital, Istanbul, Turkey | Study Director |
| Rahmet Güner, Prof. Dr. | Yıldırım Beyazıt University, Ankara City Hospital, Ankara, Turkey | Study Director |
| İsmail Y. Avcı | Gulhane Faculty of Medicine, University of Health Sciences, Ankara, Turkey | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Afyonkarahisar Health Science University | Afyonkarahisar | Turkey (Türkiye) | ||||
| Gulhane Faculty of Medicine, University of Health Sciences |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32109013 | Background | Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28. | |
| 32307245 |
| Label | URL |
|---|---|
| World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
At the beginning of the study, it was planned to have 30 patients each in the control and study groups. During the study, 6 patients were excluded from the study group because ivermectin treatments were terminated due to the detection of mutations that impairs ivermectin metabolism and new patients were added. As a result, 66 patients were included in the study, 6 patients were excluded due to mutation detection and the study was completed with 30 patients in both groups.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Control Group | 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. |
| FG001 | Study Group | 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. Ivermectin: Ivermectin 5mg/5ml solution was manufactured by NEUTEC™ Pharmaceutical Company-Turkey, under "Good Manufacturing Practices" (GMP) certification conditions. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
36 patients were included in the study group. But, 6 patients in the study group were excluded from the study and analysis because ivermectin treatments were terminated due to the detection of a mutation that impairs ivermectin metabolism. As a result, overall number of baseline participants in the study group was 30.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Control Group | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Gender Distribution of the Patients | The gender of patients (Male/female) in both groups were recorded at the time of inclusion. | Posted | Count of Participants | Participants | At the first day of the study |
|
From the beginning of the study to the end of the 10th day
In our study, it was also aimed to detect mutations that impair ivermectin metabolism and report side effects that may occur due to these mutations, and these mutations were detected in 6 patients initially included in the study group. Since these patients were excluded from the study on the first day following the mutation detection and their ivermectin treatment was discontinued, they were evaluated separately from the other patients included in the study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control Group | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Encephalopathy | Nervous system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea and vomiting | Gastrointestinal disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Dr. Nurullah Okumuş | Afyonkarahisar Health Sciences University | +90 532 4372406 | drnuri@hotmail.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 5, 2020 | Dec 3, 2020 | Prot_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 5, 2020 | Dec 3, 2020 | ICF_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 5, 2020 | Dec 19, 2020 | SAP_002.pdf |
Not provided
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D007559 | Ivermectin |
| D006886 | Hydroxychloroquine |
| C462182 | favipiravir |
| D017963 | Azithromycin |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
Not provided
Not provided
Patients who were hospitalised with a pre-diagnosis of severe COVID-19 pneumonia and thereafter diagnosis of COVID-19 was also confirmed microbiologically with polymerase chain reaction (PCR) positivity in respiratory tract samples were included into the study. They were randomized to the study and control group, respectively. Single numbered patients were accepted as study group and double numbered patients as control group
Not provided
Not provided
Not provided
Not provided
|
| At the first day of the study |
| Respiratory Rate Means of the Patients | At the beginning of the study, the respiratory rates (as per minute) of the patients were measured and the mean respiratory rate values of both groups were recorded. | At the first day of the study |
| Systolic and Diastolic Pressure Means of the Patients | At the beginning of the study, the systolic and diastolic pressures (as mmHg) of the patients were measured and the mean systolic and diastolic pressure values of both groups were recorded. | At the first day of the study |
| Number of Participants With Clinical Response | The presence of at least two of the following criteria in patients at the end of 5th day were accepted as "clinical response": Extubation in mechanically ventilated patients, respiratory rate <26/min, 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 "Sequential Organ Failure Assessment (SOFA)" score. | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
| Changes in Oxygen Saturation (SpO2) Values | Baseline SpO2 values of the patients were recorded in both groups. Then, their treatments were started and SpO2 values at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in SpO2 values on the 1st, 3rd and 5th days after the basal value calculated graphically, the change in the SpO2 value at the end of the 5th day (primary endpoint) with the baseline value was compared statistically (the results were given as p value). | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
| Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | Baseline PaO2/FiO2 ratios of the patients were recorded in both groups. Then, their treatments were started and PaO2/FiO2 ratios at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in PaO2/FiO2 ratios on the 1st, 3rd and 5th days after the basal ratio was calculated graphically, the change in the PaO2/FiO2 ratio at the end of the 5th day (primary endpoint) with the baseline value was compared statistically (the results were given as p value). | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
| Changes in Serum Lymphocyte Counts | Baseline Serum Lymphocyte counts (cell/mm^3) of the patients were recorded in both groups. Then, their treatments were started and Serum Lymphocyte counts at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in Serum Lymphocyte counts on the 1st, 3rd and 5th days after the basal level was calculated graphically, the change in the Serum Lymphocyte count at the end of the 5th day (primary endpoint) with the baseline count was compared statistically (the results were given as p value). | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
| Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | Baseline PNL/L ratio of the patients were recorded in both groups. Then, their treatments were started and PNL/L ratios at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in PNL/L ratios on the 1st, 3rd and 5th days after the basal level was calculated graphically, the change in the PNL/L ratio at the end of the 5th day (primary endpoint) with the baseline ratio was compared statistically (the results were given as p value). | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
| Changes in Serum Ferritin Levels | Baseline serum ferritin levels (mg/dL) of the patients were recorded in both groups. Then, their treatments were started and serum ferritin levels at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in serum ferritin levels on the 1st, 3rd and 5th days after the basal level was calculated graphically, the change in the serum ferritin level at the end of the 5th day (primary endpoint) with the baseline level was compared statistically (the results were given as p value). | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
| Changes in Serum D-dimer Levels | Baseline serum D-dimer levels (mg/L) of the patients were recorded in both groups. Then, their treatments were started and serum D-dimer levels at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in serum D-dimer levels on the 1st, 3rd and 5th days after the basal level was calculated graphically, the change in the serum D-dimer level at the end of the 5th day (primary endpoint) with the baseline level was compared statistically (the results were given as p value). | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
| Genetic Examination of Haplotypes and Mutations That Cause Function Losing for Ivermectin Metabolism | A blood sample was taken from the patients included in the study group, after taking or during the first dose of ivermectin. From the blood samples, haplotypes and mutations that cause the function losing were investigated by performing sequence analysis of multidrug resistance 1 (MDR1)/ABCB1 and CYP3A4 genes with Sanger method. In case of detection of mutation, the patient were excluded from the study and if observed, side effects of ivermectin were noted. | At the first day of ivermectin therapy (1st day) |
| Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Adverse effects of ivermectin and drugs other than ivermectin (Hydroxychloroquine, favipiravir, azithromycin) were evaluated in the patients in the study group and and the number of participants were noted. Adverse effects of drugs other than ivermectin (Hydroxychloroquine, favipiravir, azithromycin) were evaluated in the patients in the control group and and the number of participants were noted. | At the first 5 days of study |
| Mortality | The number of died patients were evaluated in study and control groups | Through study completion, an average of 3 months |
| Changes in Oxygen Saturation (SpO2) Values | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). SpO2 values at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in SpO2 values on the 6th, 8th and 10th days was calculated graphically, the change in the SpO2 value at the end of the 10th day (secondary endpoint) with the baseline value was compared statistically (the results were given as p value). | From 6th to the end of 10th day |
| Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). PaO2/FiO2 ratios at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in PaO2/FiO2 ratios on the 6th, 8th and 10th days was calculated graphically, the change in the PaO2/FiO2 ratio at the end of the 10th day (secondary endpoint) with the baseline ratio was compared statistically (the results were given as p value). | From 6th to the end of 10th day |
| Changes in Serum Lymphocyte Counts | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). Serum lymphocyte counts (cell/mm^3) at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in serum lymphocyte counts on the 6th, 8th and 10th days was calculated graphically, the change in the serum lymphocyte count at the end of the 10th day (secondary endpoint) with the baseline value was compared statistically (the results were given as p value). | From 6th to the end of 10th day |
| Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). PNL/L ratios at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in PNL/L ratios on the 6th, 8th and 10th days was calculated graphically, the change in the PNL/L ratio at the end of the 10th day (secondary endpoint) with the baseline value was compared statistically (the results were given as p value). | From 6th to the end of 10th day |
| Changes in Serum Ferritin Levels | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). Serum ferritin levels (mg/dL) at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in serum ferritin levels on the 6th, 8th and 10th days was calculated graphically, the change in the serum ferritin level at the end of the 10th day (secondary endpoint) with the baseline value was compared statistically (the results were given as p value). | From 6th to the end of 10th day |
| Changes in Serum D-dimer Levels | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). Serum D-dimer levels (mg/L) at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in Serum D-dimer levels on the 6th, 8th and 10th days was calculated graphically, the change in the serum D-dimer level at the end of the 10th day (secondary endpoint) with the baseline value was compared statistically (the results were given as p value). | From 6th to the end of 10th day |
| Rate of COVID-19 Polymerase Chain Reaction (PCR) Test Negativity | At the end of the follow-up period (10th day), patients in the study and control group were investigated by PCR test for SARS-CoV-2 and the negative results were recorded as percentage for both groups. | At the end of 10th day |
| Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Adverse effects of ivermectin and drugs other than ivermectin (Hydroxychloroquine, favipiravir, azithromycin) were evaluated in the patients in the study group and and the number of participants were noted. Adverse effects of drugs other than ivermectin (Hydroxychloroquine, favipiravir, azithromycin) were evaluated in the patients in the control group and and the number of participants were noted. | From the 6th day of study to the 10th day of study |
| Ankara |
| Turkey (Türkiye) |
| Yıldırım Beyazıt University, Ankara City Hospital | Ankara | Turkey (Türkiye) |
| Haydarpasa Sultan Abdulhamid Han Training and Research Hospital | Istanbul | Turkey (Türkiye) |
| Background |
| Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: The reality and challenges. J Microbiol Immunol Infect. 2020 Jun;53(3):436-443. doi: 10.1016/j.jmii.2020.03.034. Epub 2020 Apr 4. |
| 27242902 | Background | Croci R, Bottaro E, Chan KW, Watanabe S, Pezzullo M, Mastrangelo E, Nastruzzi C. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin. Int J Biomater. 2016;2016:8043983. doi: 10.1155/2016/8043983. Epub 2016 May 8. |
| 32533071 | Background | 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. |
| 32251768 | Background | 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. |
| BG001 | Study Group | 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. Ivermectin: Ivermectin 5mg/5ml solution was manufactured by NEUTEC™ Pharmaceutical Company-Turkey, under "Good Manufacturing Practices" (GMP) certification conditions. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
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. Ivermectin: Ivermectin 5mg/5ml solution was manufactured by NEUTEC™ Pharmaceutical Company-Turkey, under "Good Manufacturing Practices" (GMP) certification conditions. |
|
|
| Primary | Age Distribution of the Patients | The age of the patients (years) in both groups were recorded at the time of inclusion. | Posted | Mean | Standard Deviation | Years | At the first day of the study |
|
|
|
| Primary | Percentage of Patients With Accompanying Diseases | At the beginning of the study, the patients were asked whether there were any of the following accompanying diseases and the percentage of patients with accompanying disease in both groups were recorded:
| Posted | Count of Participants | Participants | At the first day of the study |
|
|
|
| Primary | Percentage of Patients With Baseline Clinical Symptoms | At the beginning of the study, the patients were asked whether there were any of the following clinical symptoms and the percentage of patients with any of the clinical symptoms in both groups were recorded:
| Posted | Count of Participants | Participants | At the first day of the study |
|
|
|
| Primary | Body Temperature Means of the Patients | At the beginning of the study, the body temperatures (as degree celcius) of the patients were measured and the mean body temperature values of both groups were recorded. | Posted | Mean | Standard Deviation | Degree celcius | At the first day of the study |
|
|
|
| Primary | Heart Rate Means of the Patients | At the beginning of the study, the heart rates (as per minute) of the patients were measured and the mean heart rate values of both groups were recorded. | Posted | Mean | Standard Deviation | beats per minute | At the first day of the study |
|
|
|
| Primary | Respiratory Rate Means of the Patients | At the beginning of the study, the respiratory rates (as per minute) of the patients were measured and the mean respiratory rate values of both groups were recorded. | Posted | Mean | Standard Deviation | breaths per minute | At the first day of the study |
|
|
|
| Primary | Systolic and Diastolic Pressure Means of the Patients | At the beginning of the study, the systolic and diastolic pressures (as mmHg) of the patients were measured and the mean systolic and diastolic pressure values of both groups were recorded. | Posted | Mean | Standard Deviation | mmHg | At the first day of the study |
|
|
|
| Primary | Number of Participants With Clinical Response | The presence of at least two of the following criteria in patients at the end of 5th day were accepted as "clinical response": Extubation in mechanically ventilated patients, respiratory rate <26/min, 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 "Sequential Organ Failure Assessment (SOFA)" score. | Posted | Count of Participants | Participants | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
|
|
|
|
| Primary | Changes in Oxygen Saturation (SpO2) Values | Baseline SpO2 values of the patients were recorded in both groups. Then, their treatments were started and SpO2 values at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in SpO2 values on the 1st, 3rd and 5th days after the basal value calculated graphically, the change in the SpO2 value at the end of the 5th day (primary endpoint) with the baseline value was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | percentage of peripheral capillary O2 | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
|
|
|
|
| Primary | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | Baseline PaO2/FiO2 ratios of the patients were recorded in both groups. Then, their treatments were started and PaO2/FiO2 ratios at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in PaO2/FiO2 ratios on the 1st, 3rd and 5th days after the basal ratio was calculated graphically, the change in the PaO2/FiO2 ratio at the end of the 5th day (primary endpoint) with the baseline value was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | Ratio | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
|
|
|
|
| Primary | Changes in Serum Lymphocyte Counts | Baseline Serum Lymphocyte counts (cell/mm^3) of the patients were recorded in both groups. Then, their treatments were started and Serum Lymphocyte counts at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in Serum Lymphocyte counts on the 1st, 3rd and 5th days after the basal level was calculated graphically, the change in the Serum Lymphocyte count at the end of the 5th day (primary endpoint) with the baseline count was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | cell/mm^3 | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
|
|
|
|
| Primary | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | Baseline PNL/L ratio of the patients were recorded in both groups. Then, their treatments were started and PNL/L ratios at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in PNL/L ratios on the 1st, 3rd and 5th days after the basal level was calculated graphically, the change in the PNL/L ratio at the end of the 5th day (primary endpoint) with the baseline ratio was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | Ratio | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
|
|
|
|
| Primary | Changes in Serum Ferritin Levels | Baseline serum ferritin levels (mg/dL) of the patients were recorded in both groups. Then, their treatments were started and serum ferritin levels at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in serum ferritin levels on the 1st, 3rd and 5th days after the basal level was calculated graphically, the change in the serum ferritin level at the end of the 5th day (primary endpoint) with the baseline level was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | mg/dL | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
|
|
|
|
| Primary | Changes in Serum D-dimer Levels | Baseline serum D-dimer levels (mg/L) of the patients were recorded in both groups. Then, their treatments were started and serum D-dimer levels at the end of the 1st (TD1), 3rd (TD3) and 5th days (TD5) were also recorded. The end of the 5th day was accepted as the primary endpoint. While the change in serum D-dimer levels on the 1st, 3rd and 5th days after the basal level was calculated graphically, the change in the serum D-dimer level at the end of the 5th day (primary endpoint) with the baseline level was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | mg/L | From starting to the end of ivermectin therapy (0 to the end of 5th day) |
|
|
|
|
| Primary | Genetic Examination of Haplotypes and Mutations That Cause Function Losing for Ivermectin Metabolism | A blood sample was taken from the patients included in the study group, after taking or during the first dose of ivermectin. From the blood samples, haplotypes and mutations that cause the function losing were investigated by performing sequence analysis of multidrug resistance 1 (MDR1)/ABCB1 and CYP3A4 genes with Sanger method. In case of detection of mutation, the patient were excluded from the study and if observed, side effects of ivermectin were noted. | We aimed to investigate the effectiveness/safety of adding ivermectin to the COVID-19 treatment in patients without mutation. Since ivermectin was not given to the control group, no blood sample was taken from these patients for mutation screening. The reason why there are 36 patients in the study group in this table is to indicate that there are 6 patients who were included in the study group but were removed from the study group because of a mutation and were replaced by additional patients. | Posted | Count of Participants | Participants | At the first day of ivermectin therapy (1st day) |
|
|
|
| Primary | Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Adverse effects of ivermectin and drugs other than ivermectin (Hydroxychloroquine, favipiravir, azithromycin) were evaluated in the patients in the study group and and the number of participants were noted. Adverse effects of drugs other than ivermectin (Hydroxychloroquine, favipiravir, azithromycin) were evaluated in the patients in the control group and and the number of participants were noted. | Posted | Count of Participants | Participants | At the first 5 days of study |
|
|
|
| Secondary | Number of Participants With Clinical Response | The presence of at least two of the following criteria in patients on the 10th day were accepted as "clinical response": Respiration rate between 22-24/min, SpO2 level in room air >95%, absence of oxygen requirement, observation of radiological improvement in control lung tomography and no need for intensive care. | Posted | Count of Participants | Participants | 10 days (5 days ivermectin therapy plus 5 days follow-up) |
|
|
|
|
| Secondary | Mortality | The number of died patients were evaluated in study and control groups | Posted | Count of Participants | Participants | Through study completion, an average of 3 months |
|
|
|
|
| Secondary | Changes in Oxygen Saturation (SpO2) Values | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). SpO2 values at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in SpO2 values on the 6th, 8th and 10th days was calculated graphically, the change in the SpO2 value at the end of the 10th day (secondary endpoint) with the baseline value was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | percentage of peripheral capillary O2 | From 6th to the end of 10th day |
|
|
|
|
| Secondary | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). PaO2/FiO2 ratios at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in PaO2/FiO2 ratios on the 6th, 8th and 10th days was calculated graphically, the change in the PaO2/FiO2 ratio at the end of the 10th day (secondary endpoint) with the baseline ratio was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | Ratio | From 6th to the end of 10th day |
|
|
|
|
| Secondary | Changes in Serum Lymphocyte Counts | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). Serum lymphocyte counts (cell/mm^3) at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in serum lymphocyte counts on the 6th, 8th and 10th days was calculated graphically, the change in the serum lymphocyte count at the end of the 10th day (secondary endpoint) with the baseline value was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | cell/mm^3 | From 6th to the end of 10th day |
|
|
|
|
| Secondary | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). PNL/L ratios at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in PNL/L ratios on the 6th, 8th and 10th days was calculated graphically, the change in the PNL/L ratio at the end of the 10th day (secondary endpoint) with the baseline value was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | Ratio | From 6th to the end of 10th day |
|
|
|
|
| Secondary | Changes in Serum Ferritin Levels | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). Serum ferritin levels (mg/dL) at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in serum ferritin levels on the 6th, 8th and 10th days was calculated graphically, the change in the serum ferritin level at the end of the 10th day (secondary endpoint) with the baseline value was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | mg/dL | From 6th to the end of 10th day |
|
|
|
|
| Secondary | Changes in Serum D-dimer Levels | In both groups, after the treatment period was completed (first 5 days, primary endpoint), patients were followed up for 5 more days (follow-up period). Serum D-dimer levels (mg/L) at the end of 6th (FD1), 8th (FD3) and 10th day (FD5) were also recorded. The end of the 10th day was accepted as the secondary endpoint. While the change in Serum D-dimer levels on the 6th, 8th and 10th days was calculated graphically, the change in the serum D-dimer level at the end of the 10th day (secondary endpoint) with the baseline value was compared statistically (the results were given as p value). | Posted | Mean | Standard Deviation | mg/L | From 6th to the end of 10th day |
|
|
|
|
| Secondary | Rate of COVID-19 Polymerase Chain Reaction (PCR) Test Negativity | At the end of the follow-up period (10th day), patients in the study and control group were investigated by PCR test for SARS-CoV-2 and the negative results were recorded as percentage for both groups. | PCR test was applied to 8 patients in the control group and 16 patients in the study group at the end of the study (secondary endpoint). | Posted | Count of Participants | Participants | At the end of 10th day |
|
|
|
|
| Secondary | Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Adverse effects of ivermectin and drugs other than ivermectin (Hydroxychloroquine, favipiravir, azithromycin) were evaluated in the patients in the study group and and the number of participants were noted. Adverse effects of drugs other than ivermectin (Hydroxychloroquine, favipiravir, azithromycin) were evaluated in the patients in the control group and and the number of participants were noted. | Posted | Count of Participants | Participants | From the 6th day of study to the 10th day of study |
|
|
|
| 9 |
| 30 |
| 0 |
| 30 |
| 3 |
| 30 |
| EG001 | Study Group | 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. Ivermectin: Ivermectin 5mg/5ml solution was manufactured by NEUTEC™ Pharmaceutical Company-Turkey, under "Good Manufacturing Practices" (GMP) certification conditions. | 6 | 30 | 0 | 30 | 0 | 30 |
| EG002 | Participants With Mutations | Patients that were included in the study group and excluded from the study because one or both of the multidrug resistance 1 (MDR1) / ABCB1 and CYP3A4 genes were detected in the blood sample taken at the beginning of ivermectin treatment on the first day | 0 | 6 | 5 | 6 | 0 | 6 |
| Increase in liver function tests | Gastrointestinal disorders | Systematic Assessment |
|
Not provided
Not provided
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002738 |
| Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004917 | Erythromycin |
| Coronary artery disease |
|
| Cardiac failure |
|
| Chronic obstructive pulmonary disease |
|
| Malignancy |
|
| Immunodeficiency |
|
| Sore throat |
|
| dyspnea |
|
| Headache |
|
| Weakness |
|
| Myalgia |
|
| Diarrhea |
|
| Nausea or vomiting |
|
| TD3 |
|
| TD5 |
|
| TD3 |
|
| TD5 |
|
| TD3 |
|
| TD5 |
|
| TD3 |
|
| TD5 |
|
| TD3 |
|
| TD5 |
|
| TD3 |
|
| TD5 |
|
| FD3 |
|
| FD5 |
|
| FD3 |
|
| FD5 |
|
| FD3 |
|
| FD5 |
|
| FD3 |
|
| FD5 |
|
| FD3 |
|
| FD5 |
|
| FD3 |
|
| FD5 |
|