COVID-19
Conditions
Keywords
Ivermectin, SARS-CoV-2, Treatment
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.
Interventions
DRUGIvermectin
Ivermectin 5mg/5ml solution was manufactured by NEUTEC™ Pharmaceutical Company-Turkey, under Good Manufacturing Practices (GMP) certification conditions.
Sponsors
NeuTec Pharma
Afyonkarahisar Health Sciences University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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 study and control group, respectively. Patients with at least one of the criteria below were accepted as patients with severe COVID-19 pneumonia; 1. Presence of tachypnea ≥ 30/minute, SpO2 level \< 90% in room air, PaO2/FiO2 \<300 in oxygen receiving patient 2. Presence of specific radiological finding for COVID-19 in lung tomography (bilateral lobular, peripherally located, diffuse patchy ground glass opacities) 3. Mechanical ventilation requirement 4. Acute organ dysfunction findings; patients with SOFA (sepsis-related organ failure assessment) score \>2
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | At the first 5 days of study | 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. |
| Respiratory Rate Means of the Patients | At the first day of the study | 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. |
| Systolic and Diastolic Pressure Means of the Patients | At the first day of the study | 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. |
| Number of Participants With Clinical Response | From starting to the end of ivermectin therapy (0 to the end of 5th day) | 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. |
| Changes in Oxygen Saturation (SpO2) Values | From starting to the end of ivermectin therapy (0 to the end of 5th day) | 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). |
| Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | From starting to the end of ivermectin therapy (0 to the end of 5th day) | 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). |
| Changes in Serum Lymphocyte Counts | From starting to the end of ivermectin therapy (0 to the end of 5th day) | 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). |
| Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | From starting to the end of ivermectin therapy (0 to the end of 5th day) | 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). |
| Changes in Serum Ferritin Levels | From starting to the end of ivermectin therapy (0 to the end of 5th day) | 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). |
| Changes in Serum D-dimer Levels | From starting to the end of ivermectin therapy (0 to the end of 5th day) | 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). |
| Genetic Examination of Haplotypes and Mutations That Cause Function Losing for Ivermectin Metabolism | At the first day of ivermectin therapy (1st day) | 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. |
| Gender Distribution of the Patients | At the first day of the study | The gender of patients (Male/female) in both groups were recorded at the time of inclusion. |
| Age Distribution of the Patients | At the first day of the study | The age of the patients (years) in both groups were recorded at the time of inclusion. |
| Percentage of Patients With Accompanying Diseases | At the first day of the study | 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: * Diabetes mellitus * Hypertension * Coronary artery disease * Cardiac failure * Chronic obstructive pulmonary disease * Malignancy * Immunodeficiency |
| Percentage of Patients With Baseline Clinical Symptoms | At the first day of the study | 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: * Fever * Cough * Sore throat * Dispnea * Headache * Weakness * Myalgia * Diarrhea * Nausea or vomiting |
| Body Temperature Means of the Patients | At the first day of the study | 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. |
| Heart Rate Means of the Patients | At the first day of the study | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | Through study completion, an average of 3 months | The number of died patients were evaluated in study and control groups |
| Changes in Oxygen Saturation (SpO2) Values | From 6th to the end of 10th day | 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). |
| Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | From 6th to the end of 10th day | 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). |
| Changes in Serum Lymphocyte Counts | From 6th to the end of 10th day | 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). |
| Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | From 6th to the end of 10th day | 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). |
| Changes in Serum Ferritin Levels | From 6th to the end of 10th day | 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). |
| Changes in Serum D-dimer Levels | From 6th to the end of 10th day | 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). |
| Rate of COVID-19 Polymerase Chain Reaction (PCR) Test Negativity | At the end of 10th day | 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. |
| Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | From the 6th day of study to the 10th day of study | 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. |
| Number of Participants With Clinical Response | 10 days (5 days ivermectin therapy plus 5 days follow-up) | 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. |
Countries
Turkey (Türkiye)
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 30 |
| 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. | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Mutation disrupting ivermectin metabolism was found in 6 patients | 0 | 6 |
Baseline characteristics
| Characteristic | Control Group | Total | Study Group |
|---|---|---|---|
| Age, Customized | 66.23 years STANDARD_DEVIATION 13.31 | 62.20 years STANDARD_DEVIATION 13 | 58.17 years STANDARD_DEVIATION 11.52 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 30 Participants | 60 Participants | 30 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Turkey | 30 participants | 60 participants | 30 participants |
| Sex: Female, Male Female | 11 Participants | 20 Participants | 9 Participants |
| Sex: Female, Male Male | 19 Participants | 40 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 30 | 6 / 30 | 0 / 6 |
| other Total, other adverse events | 3 / 30 | 0 / 30 | 0 / 6 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 5 / 6 |
Outcome results
Primary
Age Distribution of the Patients
The age of the patients (years) in both groups were recorded at the time of inclusion.
Time frame: At the first day of the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Age Distribution of the Patients | 66.23 Years | Standard Deviation 13.31 |
| Study Group | Age Distribution of the Patients | 58.17 Years | Standard Deviation 11.52 |
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.
Time frame: At the first day of the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Body Temperature Means of the Patients | 36.8 Degree celcius | Standard Deviation 0.8 |
| Study Group | Body Temperature Means of the Patients | 36.9 Degree celcius | Standard Deviation 0.7 |
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).
Time frame: From starting to the end of ivermectin therapy (0 to the end of 5th day)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in Oxygen Saturation (SpO2) Values | Baseline | 89.67 percentage of peripheral capillary O2 | Standard Deviation 5.09 |
| Control Group | Changes in Oxygen Saturation (SpO2) Values | TD1 | 90.50 percentage of peripheral capillary O2 | Standard Deviation 7.47 |
| Control Group | Changes in Oxygen Saturation (SpO2) Values | TD3 | 91.90 percentage of peripheral capillary O2 | Standard Deviation 4.97 |
| Control Group | Changes in Oxygen Saturation (SpO2) Values | TD5 | 93.00 percentage of peripheral capillary O2 | Standard Deviation 3.25 |
| Study Group | Changes in Oxygen Saturation (SpO2) Values | TD5 | 93.52 percentage of peripheral capillary O2 | Standard Deviation 4.36 |
| Study Group | Changes in Oxygen Saturation (SpO2) Values | Baseline | 89.93 percentage of peripheral capillary O2 | Standard Deviation 6.51 |
| Study Group | Changes in Oxygen Saturation (SpO2) Values | TD3 | 93.07 percentage of peripheral capillary O2 | Standard Deviation 4.12 |
| Study Group | Changes in Oxygen Saturation (SpO2) Values | TD1 | 92.85 percentage of peripheral capillary O2 | Standard Deviation 4.86 |
p-value: 0.14Wilcoxon (Mann-Whitney)
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).
Time frame: From starting to the end of ivermectin therapy (0 to the end of 5th day)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in Serum D-dimer Levels | Baseline | 1.32 mg/L | Standard Deviation 2.04 |
| Control Group | Changes in Serum D-dimer Levels | TD1 | 2.80 mg/L | Standard Deviation 5.66 |
| Control Group | Changes in Serum D-dimer Levels | TD3 | 4.14 mg/L | Standard Deviation 9.91 |
| Control Group | Changes in Serum D-dimer Levels | TD5 | 3.58 mg/L | Standard Deviation 8.27 |
| Study Group | Changes in Serum D-dimer Levels | TD5 | 5.85 mg/L | Standard Deviation 5.28 |
| Study Group | Changes in Serum D-dimer Levels | Baseline | 1.25 mg/L | Standard Deviation 1.71 |
| Study Group | Changes in Serum D-dimer Levels | TD3 | 3.24 mg/L | Standard Deviation 11.6 |
| Study Group | Changes in Serum D-dimer Levels | TD1 | 1.40 mg/L | Standard Deviation 1.73 |
p-value: 0.22Wilcoxon (Mann-Whitney)
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).
Time frame: From starting to the end of ivermectin therapy (0 to the end of 5th day)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in Serum Ferritin Levels | Baseline | 747.05 mg/dL | Standard Deviation 800.54 |
| Control Group | Changes in Serum Ferritin Levels | TD1 | 783.03 mg/dL | Standard Deviation 827.1 |
| Control Group | Changes in Serum Ferritin Levels | TD3 | 881.17 mg/dL | Standard Deviation 779.95 |
| Control Group | Changes in Serum Ferritin Levels | TD5 | 1028.24 mg/dL | Standard Deviation 777.08 |
| Study Group | Changes in Serum Ferritin Levels | TD5 | 875.12 mg/dL | Standard Deviation 1193.06 |
| Study Group | Changes in Serum Ferritin Levels | Baseline | 682.75 mg/dL | Standard Deviation 470.08 |
| Study Group | Changes in Serum Ferritin Levels | TD3 | 875.90 mg/dL | Standard Deviation 694.52 |
| Study Group | Changes in Serum Ferritin Levels | TD1 | 834.94 mg/dL | Standard Deviation 624.12 |
p-value: 0.12Wilcoxon (Mann-Whitney)
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).
Time frame: From starting to the end of ivermectin therapy (0 to the end of 5th day)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in Serum Lymphocyte Counts | TD5 | 968 cell/mm^3 | Standard Deviation 477 |
| Control Group | Changes in Serum Lymphocyte Counts | TD1 | 1034 cell/mm^3 | Standard Deviation 450 |
| Control Group | Changes in Serum Lymphocyte Counts | Baseline | 1010 cell/mm^3 | Standard Deviation 438 |
| Control Group | Changes in Serum Lymphocyte Counts | TD3 | 977 cell/mm^3 | Standard Deviation 575 |
| Study Group | Changes in Serum Lymphocyte Counts | Baseline | 932 cell/mm^3 | Standard Deviation 483 |
| Study Group | Changes in Serum Lymphocyte Counts | TD5 | 1273 cell/mm^3 | Standard Deviation 822 |
| Study Group | Changes in Serum Lymphocyte Counts | TD3 | 1021 cell/mm^3 | Standard Deviation 648 |
| Study Group | Changes in Serum Lymphocyte Counts | TD1 | 928 cell/mm^3 | Standard Deviation 607 |
p-value: 0.15Wilcoxon (Mann-Whitney)
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).
Time frame: From starting to the end of ivermectin therapy (0 to the end of 5th day)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | Baseline | 197.44 Ratio | Standard Deviation 102.31 |
| Control Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | TD3 | 174.77 Ratio | Standard Deviation 94.74 |
| Control Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | TD1 | 181.83 Ratio | Standard Deviation 99.62 |
| Control Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | TD5 | 180.13 Ratio | Standard Deviation 95.43 |
| Study Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | TD5 | 178.94 Ratio | Standard Deviation 98.21 |
| Study Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | Baseline | 158.83 Ratio | Standard Deviation 88.15 |
| Study Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | TD1 | 147.31 Ratio | Standard Deviation 74.15 |
| Study Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | TD3 | 147.74 Ratio | Standard Deviation 83.3 |
p-value: 0.68Wilcoxon (Mann-Whitney)
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).
Time frame: From starting to the end of ivermectin therapy (0 to the end of 5th day)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | Baseline | 7.48 Ratio | Standard Deviation 6.41 |
| Control Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | TD1 | 7.74 Ratio | Standard Deviation 7.47 |
| Control Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | TD3 | 9.26 Ratio | Standard Deviation 7.58 |
| Control Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | TD5 | 9.88 Ratio | Standard Deviation 8.45 |
| Study Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | TD5 | 7.16 Ratio | Standard Deviation 4.97 |
| Study Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | Baseline | 8.77 Ratio | Standard Deviation 8.35 |
| Study Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | TD3 | 9.02 Ratio | Standard Deviation 13.08 |
| Study Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | TD1 | 10.82 Ratio | Standard Deviation 8.55 |
p-value: 0.37Wilcoxon (Mann-Whitney)
Primary
Gender Distribution of the Patients
The gender of patients (Male/female) in both groups were recorded at the time of inclusion.
Time frame: At the first day of the study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Group | Gender Distribution of the Patients | Male | 19 Participants |
| Control Group | Gender Distribution of the Patients | Female | 11 Participants |
| Study Group | Gender Distribution of the Patients | Male | 21 Participants |
| Study Group | Gender Distribution of the Patients | Female | 9 Participants |
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.
Time frame: At the first day of ivermectin therapy (1st day)
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Group | Genetic Examination of Haplotypes and Mutations That Cause Function Losing for Ivermectin Metabolism | Mutation positive | 0 Participants |
| Control Group | Genetic Examination of Haplotypes and Mutations That Cause Function Losing for Ivermectin Metabolism | Mutation negative | 0 Participants |
| Study Group | Genetic Examination of Haplotypes and Mutations That Cause Function Losing for Ivermectin Metabolism | Mutation positive | 6 Participants |
| Study Group | Genetic Examination of Haplotypes and Mutations That Cause Function Losing for Ivermectin Metabolism | Mutation negative | 30 Participants |
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.
Time frame: At the first day of the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Heart Rate Means of the Patients | 92 beats per minute | Standard Deviation 18 |
| Study Group | Heart Rate Means of the Patients | 88 beats per minute | Standard Deviation 12 |
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.
Time frame: From starting to the end of ivermectin therapy (0 to the end of 5th day)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group | Number of Participants With Clinical Response | 11 Participants |
| Study Group | Number of Participants With Clinical Response | 14 Participants |
p-value: 0.43Chi-squared
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: * Diabetes mellitus * Hypertension * Coronary artery disease * Cardiac failure * Chronic obstructive pulmonary disease * Malignancy * Immunodeficiency
Time frame: At the first day of the study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Group | Percentage of Patients With Accompanying Diseases | Cardiac failure | 1 Participants |
| Control Group | Percentage of Patients With Accompanying Diseases | Diabetes Mellitus | 10 Participants |
| Control Group | Percentage of Patients With Accompanying Diseases | Malignancy | 1 Participants |
| Control Group | Percentage of Patients With Accompanying Diseases | Immunodeficiency | 1 Participants |
| Control Group | Percentage of Patients With Accompanying Diseases | Hypertension | 12 Participants |
| Control Group | Percentage of Patients With Accompanying Diseases | Coronary artery disease | 8 Participants |
| Control Group | Percentage of Patients With Accompanying Diseases | Chronic obstructive pulmonary disease | 3 Participants |
| Study Group | Percentage of Patients With Accompanying Diseases | Cardiac failure | 0 Participants |
| Study Group | Percentage of Patients With Accompanying Diseases | Hypertension | 15 Participants |
| Study Group | Percentage of Patients With Accompanying Diseases | Diabetes Mellitus | 9 Participants |
| Study Group | Percentage of Patients With Accompanying Diseases | Chronic obstructive pulmonary disease | 6 Participants |
| Study Group | Percentage of Patients With Accompanying Diseases | Malignancy | 0 Participants |
| Study Group | Percentage of Patients With Accompanying Diseases | Coronary artery disease | 5 Participants |
| Study Group | Percentage of Patients With Accompanying Diseases | Immunodeficiency | 0 Participants |
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: * Fever * Cough * Sore throat * Dispnea * Headache * Weakness * Myalgia * Diarrhea * Nausea or vomiting
Time frame: At the first day of the study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Group | Percentage of Patients With Baseline Clinical Symptoms | Headache | 2 Participants |
| Control Group | Percentage of Patients With Baseline Clinical Symptoms | Weakness | 11 Participants |
| Control Group | Percentage of Patients With Baseline Clinical Symptoms | Cough | 14 Participants |
| Control Group | Percentage of Patients With Baseline Clinical Symptoms | Myalgia | 7 Participants |
| Control Group | Percentage of Patients With Baseline Clinical Symptoms | Sore throat | 1 Participants |
| Control Group | Percentage of Patients With Baseline Clinical Symptoms | Diarrhea | 0 Participants |
| Control Group | Percentage of Patients With Baseline Clinical Symptoms | Fever | 13 Participants |
| Control Group | Percentage of Patients With Baseline Clinical Symptoms | Nausea or vomiting | 0 Participants |
| Control Group | Percentage of Patients With Baseline Clinical Symptoms | dyspnea | 19 Participants |
| Study Group | Percentage of Patients With Baseline Clinical Symptoms | Nausea or vomiting | 1 Participants |
| Study Group | Percentage of Patients With Baseline Clinical Symptoms | Headache | 5 Participants |
| Study Group | Percentage of Patients With Baseline Clinical Symptoms | Fever | 15 Participants |
| Study Group | Percentage of Patients With Baseline Clinical Symptoms | Sore throat | 3 Participants |
| Study Group | Percentage of Patients With Baseline Clinical Symptoms | dyspnea | 23 Participants |
| Study Group | Percentage of Patients With Baseline Clinical Symptoms | Weakness | 13 Participants |
| Study Group | Percentage of Patients With Baseline Clinical Symptoms | Myalgia | 9 Participants |
| Study Group | Percentage of Patients With Baseline Clinical Symptoms | Diarrhea | 1 Participants |
| Study Group | Percentage of Patients With Baseline Clinical Symptoms | Cough | 16 Participants |
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.
Time frame: At the first day of the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Respiratory Rate Means of the Patients | 24.7 breaths per minute | Standard Deviation 0.7 |
| Study Group | Respiratory Rate Means of the Patients | 24 breaths per minute | Standard Deviation 5 |
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.
Time frame: At the first day of the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Systolic and Diastolic Pressure Means of the Patients | Systolic pressure | 124.61 mmHg | Standard Deviation 15.37 |
| Control Group | Systolic and Diastolic Pressure Means of the Patients | Diastolic pressure | 73.43 mmHg | Standard Deviation 8.47 |
| Study Group | Systolic and Diastolic Pressure Means of the Patients | Systolic pressure | 124.39 mmHg | Standard Deviation 15.6 |
| Study Group | Systolic and Diastolic Pressure Means of the Patients | Diastolic pressure | 75.64 mmHg | Standard Deviation 9.79 |
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.
Time frame: At the first 5 days of study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Group | Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Nausea and vomiting | 2 Participants |
| Control Group | Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Increase in liver function tests | 1 Participants |
| Study Group | Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Nausea and vomiting | 0 Participants |
| Study Group | Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Increase in liver function tests | 0 Participants |
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).
Time frame: From 6th to the end of 10th day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in Oxygen Saturation (SpO2) Values | Baseline | 89.67 percentage of peripheral capillary O2 | Standard Deviation 5.09 |
| Control Group | Changes in Oxygen Saturation (SpO2) Values | FD1 | 92.43 percentage of peripheral capillary O2 | Standard Deviation 2.86 |
| Control Group | Changes in Oxygen Saturation (SpO2) Values | FD3 | 92.91 percentage of peripheral capillary O2 | Standard Deviation 2.71 |
| Control Group | Changes in Oxygen Saturation (SpO2) Values | FD5 | 93.00 percentage of peripheral capillary O2 | Standard Deviation 3.93 |
| Study Group | Changes in Oxygen Saturation (SpO2) Values | FD5 | 95.35 percentage of peripheral capillary O2 | Standard Deviation 2.72 |
| Study Group | Changes in Oxygen Saturation (SpO2) Values | Baseline | 89.93 percentage of peripheral capillary O2 | Standard Deviation 6.51 |
| Study Group | Changes in Oxygen Saturation (SpO2) Values | FD3 | 94.24 percentage of peripheral capillary O2 | Standard Deviation 2.76 |
| Study Group | Changes in Oxygen Saturation (SpO2) Values | FD1 | 94.54 percentage of peripheral capillary O2 | Standard Deviation 2.21 |
p-value: 0.03Wilcoxon (Mann-Whitney)
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).
Time frame: From 6th to the end of 10th day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in Serum D-dimer Levels | Baseline | 1.32 mg/L | Standard Deviation 2.04 |
| Control Group | Changes in Serum D-dimer Levels | FD1 | 3.45 mg/L | Standard Deviation 6.6 |
| Control Group | Changes in Serum D-dimer Levels | FD3 | 1.63 mg/L | Standard Deviation 1.38 |
| Control Group | Changes in Serum D-dimer Levels | FD5 | 1.49 mg/L | Standard Deviation 2.28 |
| Study Group | Changes in Serum D-dimer Levels | FD5 | 0.71 mg/L | Standard Deviation 0.96 |
| Study Group | Changes in Serum D-dimer Levels | Baseline | 1.25 mg/L | Standard Deviation 1.71 |
| Study Group | Changes in Serum D-dimer Levels | FD3 | 0.89 mg/L | Standard Deviation 2.45 |
| Study Group | Changes in Serum D-dimer Levels | FD1 | 1.37 mg/L | Standard Deviation 2.53 |
p-value: 0.03Wilcoxon (Mann-Whitney)
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).
Time frame: From 6th to the end of 10th day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in Serum Ferritin Levels | Baseline | 747.05 mg/dL | Standard Deviation 800.54 |
| Control Group | Changes in Serum Ferritin Levels | FD1 | 1076.88 mg/dL | Standard Deviation 704.05 |
| Control Group | Changes in Serum Ferritin Levels | FD3 | 1097.57 mg/dL | Standard Deviation 595.22 |
| Control Group | Changes in Serum Ferritin Levels | FD5 | 1206.90 mg/dL | Standard Deviation 782.84 |
| Study Group | Changes in Serum Ferritin Levels | FD5 | 494.71 mg/dL | Standard Deviation 349.78 |
| Study Group | Changes in Serum Ferritin Levels | Baseline | 682.75 mg/dL | Standard Deviation 470.08 |
| Study Group | Changes in Serum Ferritin Levels | FD3 | 433.48 mg/dL | Standard Deviation 641.82 |
| Study Group | Changes in Serum Ferritin Levels | FD1 | 628.45 mg/dL | Standard Deviation 580.1 |
p-value: 0.005Wilcoxon (Mann-Whitney)
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).
Time frame: From 6th to the end of 10th day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in Serum Lymphocyte Counts | Baseline | 1010 cell/mm^3 | Standard Deviation 438 |
| Control Group | Changes in Serum Lymphocyte Counts | FD3 | 1086 cell/mm^3 | Standard Deviation 880 |
| Control Group | Changes in Serum Lymphocyte Counts | FD1 | 916 cell/mm^3 | Standard Deviation 411 |
| Control Group | Changes in Serum Lymphocyte Counts | FD5 | 1256 cell/mm^3 | Standard Deviation 710 |
| Study Group | Changes in Serum Lymphocyte Counts | FD5 | 1698 cell/mm^3 | Standard Deviation 1438 |
| Study Group | Changes in Serum Lymphocyte Counts | Baseline | 932 cell/mm^3 | Standard Deviation 483 |
| Study Group | Changes in Serum Lymphocyte Counts | FD1 | 1403 cell/mm^3 | Standard Deviation 869 |
| Study Group | Changes in Serum Lymphocyte Counts | FD3 | 1668 cell/mm^3 | Standard Deviation 819 |
p-value: 0.24Wilcoxon (Mann-Whitney)
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).
Time frame: From 6th to the end of 10th day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | Baseline | 197.44 Ratio | Standard Deviation 102.31 |
| Control Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | FD1 | 204.28 Ratio | Standard Deviation 109.51 |
| Control Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | FD3 | 211.75 Ratio | Standard Deviation 127.62 |
| Control Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | FD5 | 220.78 Ratio | Standard Deviation 127.26 |
| Study Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | FD5 | 236.33 Ratio | Standard Deviation 85.66 |
| Study Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | Baseline | 158.83 Ratio | Standard Deviation 88.15 |
| Study Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | FD3 | 227.43 Ratio | Standard Deviation 103.71 |
| Study Group | Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2) | FD1 | 199.83 Ratio | Standard Deviation 85.02 |
p-value: 0.39Wilcoxon (Mann-Whitney)
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).
Time frame: From 6th to the end of 10th day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | Baseline | 7.48 Ratio | Standard Deviation 6.41 |
| Control Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | FD1 | 10.49 Ratio | Standard Deviation 7.1 |
| Control Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | FD3 | 9.66 Ratio | Standard Deviation 10.99 |
| Control Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | FD5 | 6.19 Ratio | Standard Deviation 4.85 |
| Study Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | FD5 | 7.34 Ratio | Standard Deviation 8.09 |
| Study Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | Baseline | 8.77 Ratio | Standard Deviation 8.35 |
| Study Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | FD3 | 5.81 Ratio | Standard Deviation 9.99 |
| Study Group | Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L) | FD1 | 6.90 Ratio | Standard Deviation 11.84 |
p-value: 0.56Wilcoxon (Mann-Whitney)
Secondary
Mortality
The number of died patients were evaluated in study and control groups
Time frame: Through study completion, an average of 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group | Mortality | 9 Participants |
| Study Group | Mortality | 6 Participants |
p-value: 0.37Chi-squared
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.
Time frame: 10 days (5 days ivermectin therapy plus 5 days follow-up)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group | Number of Participants With Clinical Response | 16 Participants |
| Study Group | Number of Participants With Clinical Response | 22 Participants |
p-value: 0.1Chi-squared
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.
Time frame: At the end of 10th day
Population: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group | Rate of COVID-19 Polymerase Chain Reaction (PCR) Test Negativity | 3 Participants |
| Study Group | Rate of COVID-19 Polymerase Chain Reaction (PCR) Test Negativity | 14 Participants |
p-value: 0.01Chi-squared
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.
Time frame: From the 6th day of study to the 10th day of study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group | Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | 0 Participants |
| Study Group | Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | 0 Participants |