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Trial record 2 of 81 for:    ivermectin | COVID-19

Ivermectin for Severe COVID-19 Management

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ClinicalTrials.gov Identifier: NCT04646109
Recruitment Status : Completed
First Posted : November 27, 2020
Results First Posted : January 27, 2021
Last Update Posted : January 27, 2021
Sponsor:
Collaborator:
NeuTec Pharma
Information provided by (Responsible Party):
Nurullah Okumuş, Afyonkarahisar Health Sciences University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition COVID-19
Intervention Drug: Ivermectin
Enrollment 66
Recruitment Details  
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.
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Period Title: Overall Study
Started 30 36
Completed 30 30
Not Completed 0 6
Reason Not Completed
Mutation disrupting ivermectin metabolism was found in 6 patients             0             6
Arm/Group Title Control Group Study Group Total
Hide Arm/Group 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 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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 30 30 60
Hide Baseline Analysis Population Description
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.
Age, Customized  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 30 participants 60 participants
66.23  (13.31) 58.17  (11.52) 62.20  (13.00)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
Female
11
  36.7%
9
  30.0%
20
  33.3%
Male
19
  63.3%
21
  70.0%
40
  66.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
30
 100.0%
30
 100.0%
60
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Turkey Number Analyzed 30 participants 30 participants 60 participants
30 30 60
1.Primary Outcome
Title Gender Distribution of the Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
Male
19
  63.3%
21
  70.0%
Female
11
  36.7%
9
  30.0%
2.Primary Outcome
Title Age Distribution of the Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: Years
66.23  (13.31) 58.17  (11.52)
3.Primary Outcome
Title Percentage of Patients With Accompanying Diseases
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
Diabetes Mellitus
10
  33.3%
9
  30.0%
Hypertension
12
  40.0%
15
  50.0%
Coronary artery disease
8
  26.7%
5
  16.7%
Cardiac failure
1
   3.3%
0
   0.0%
Chronic obstructive pulmonary disease
3
  10.0%
6
  20.0%
Malignancy
1
   3.3%
0
   0.0%
Immunodeficiency
1
   3.3%
0
   0.0%
4.Primary Outcome
Title Percentage of Patients With Baseline Clinical Symptoms
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
Fever
13
  43.3%
15
  50.0%
Cough
14
  46.7%
16
  53.3%
Sore throat
1
   3.3%
3
  10.0%
dyspnea
19
  63.3%
23
  76.7%
Headache
2
   6.7%
5
  16.7%
Weakness
11
  36.7%
13
  43.3%
Myalgia
7
  23.3%
9
  30.0%
Diarrhea
0
   0.0%
1
   3.3%
Nausea or vomiting
0
   0.0%
1
   3.3%
5.Primary Outcome
Title Body Temperature Means of the Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: Degree celcius
36.8  (0.8) 36.9  (0.7)
6.Primary Outcome
Title Heart Rate Means of the Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: beats per minute
92  (18) 88  (12)
7.Primary Outcome
Title Respiratory Rate Means of the Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: breaths per minute
24.7  (0.7) 24  (5)
8.Primary Outcome
Title Systolic and Diastolic Pressure Means of the Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: mmHg
Systolic pressure 124.61  (15.37) 124.39  (15.60)
Diastolic pressure 73.43  (8.47) 75.64  (9.79)
9.Primary Outcome
Title Number of Participants With Clinical Response
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
11
  36.7%
14
  46.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments A p<0.05 value was considered statistically significant
Method Chi-squared
Comments [Not Specified]
10.Primary Outcome
Title Changes in Oxygen Saturation (SpO2) Values
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: percentage of peripheral capillary O2
Baseline 89.67  (5.09) 89.93  (6.51)
TD1 90.50  (7.47) 92.85  (4.86)
TD3 91.90  (4.97) 93.07  (4.12)
TD5 93.00  (3.25) 93.52  (4.36)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
11.Primary Outcome
Title Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: Ratio
Baseline 197.44  (102.31) 158.83  (88.15)
TD1 181.83  (99.62) 147.31  (74.15)
TD3 174.77  (94.74) 147.74  (83.30)
TD5 180.13  (95.43) 178.94  (98.21)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
12.Primary Outcome
Title Changes in Serum Lymphocyte Counts
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: cell/mm^3
Baseline 1010  (438) 932  (483)
TD1 1034  (450) 928  (607)
TD3 977  (575) 1021  (648)
TD5 968  (477) 1273  (822)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
13.Primary Outcome
Title Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: Ratio
Baseline 7.48  (6.41) 8.77  (8.35)
TD1 7.74  (7.47) 10.82  (8.55)
TD3 9.26  (7.58) 9.02  (13.08)
TD5 9.88  (8.45) 7.16  (4.97)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
14.Primary Outcome
Title Changes in Serum Ferritin Levels
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 747.05  (800.54) 682.75  (470.08)
TD1 783.03  (827.10) 834.94  (624.12)
TD3 881.17  (779.95) 875.90  (694.52)
TD5 1028.24  (777.08) 875.12  (1193.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
15.Primary Outcome
Title Changes in Serum D-dimer Levels
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: mg/L
Baseline 1.32  (2.04) 1.25  (1.71)
TD1 2.80  (5.66) 1.40  (1.73)
TD3 4.14  (9.91) 3.24  (11.60)
TD5 3.58  (8.27) 5.85  (5.28)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
16.Primary Outcome
Title Genetic Examination of Haplotypes and Mutations That Cause Function Losing for Ivermectin Metabolism
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 0 36
Measure Type: Count of Participants
Unit of Measure: Participants
Mutation positive 0
6
  16.7%
Mutation negative 0
30
  83.3%
17.Primary Outcome
Title Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
Nausea and vomiting
2
   6.7%
0
   0.0%
Increase in liver function tests
1
   3.3%
0
   0.0%
18.Secondary Outcome
Title Number of Participants With Clinical Response
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
16
  53.3%
22
  73.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments A p<0.05 value was considered statistically significant
Method Chi-squared
Comments [Not Specified]
19.Secondary Outcome
Title Mortality
Hide Description The number of died patients were evaluated in study and control groups
Time Frame Through study completion, an average of 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
9
  30.0%
6
  20.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments A p<0.05 value was considered statistically significant
Method Chi-squared
Comments [Not Specified]
20.Secondary Outcome
Title Changes in Oxygen Saturation (SpO2) Values
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: percentage of peripheral capillary O2
Baseline 89.67  (5.09) 89.93  (6.51)
FD1 92.43  (2.86) 94.54  (2.21)
FD3 92.91  (2.71) 94.24  (2.76)
FD5 93.00  (3.93) 95.35  (2.72)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
21.Secondary Outcome
Title Changes in the Ratio of Partial Pressure of Oxygen (PaO2) to Fraction of Inspired Oxygen (FiO2) (PaO2/FiO2)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: Ratio
Baseline 197.44  (102.31) 158.83  (88.15)
FD1 204.28  (109.51) 199.83  (85.02)
FD3 211.75  (127.62) 227.43  (103.71)
FD5 220.78  (127.26) 236.33  (85.66)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
22.Secondary Outcome
Title Changes in Serum Lymphocyte Counts
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: cell/mm^3
Baseline 1010  (438) 932  (483)
FD1 916  (411) 1403  (869)
FD3 1086  (880) 1668  (819)
FD5 1256  (710) 1698  (1438)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.24
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
23.Secondary Outcome
Title Changes in the Ratio of Polymorphonuclear Leukocyte Count to Lymphocyte Count (PNL/L)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: Ratio
Baseline 7.48  (6.41) 8.77  (8.35)
FD1 10.49  (7.10) 6.90  (11.84)
FD3 9.66  (10.99) 5.81  (9.99)
FD5 6.19  (4.85) 7.34  (8.09)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
24.Secondary Outcome
Title Changes in Serum Ferritin Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 747.05  (800.54) 682.75  (470.08)
FD1 1076.88  (704.05) 628.45  (580.10)
FD3 1097.57  (595.22) 433.48  (641.82)
FD5 1206.90  (782.84) 494.71  (349.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
25.Secondary Outcome
Title Changes in Serum D-dimer Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: mg/L
Baseline 1.32  (2.04) 1.25  (1.71)
FD1 3.45  (6.60) 1.37  (2.53)
FD3 1.63  (1.38) 0.89  (2.45)
FD5 1.49  (2.28) 0.71  (0.96)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments A p<0.05 value was considered statistically significant
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
26.Secondary Outcome
Title Rate of COVID-19 Polymerase Chain Reaction (PCR) Test Negativity
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 8 16
Measure Type: Count of Participants
Unit of Measure: Participants
3
  37.5%
14
  87.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Control Group, Study Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments A p<0.05 value was considered statistically significant
Method Chi-squared
Comments [Not Specified]
27.Secondary Outcome
Title Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Group Study Group
Hide Arm/Group 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 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.

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.

Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
Time Frame From the beginning of the study to the end of the 10th day
Adverse Event Reporting Description 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.
 
Arm/Group Title Control Group Study Group Participants With Mutations
Hide Arm/Group 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 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.

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.

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
All-Cause Mortality
Control Group Study Group Participants With Mutations
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/30 (30.00%)      6/30 (20.00%)      0/6 (0.00%)    
Hide Serious Adverse Events
Control Group Study Group Participants With Mutations
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/30 (0.00%)      0/30 (0.00%)      5/6 (83.33%)    
Nervous system disorders       
Encephalopathy   0/30 (0.00%)  0/30 (0.00%)  5/6 (83.33%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Control Group Study Group Participants With Mutations
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/30 (10.00%)      0/30 (0.00%)      0/6 (0.00%)    
Gastrointestinal disorders       
Nausea and vomiting   2/30 (6.67%)  2 0/30 (0.00%)  0 0/6 (0.00%)  0
Increase in liver function tests   1/30 (3.33%)  1 0/30 (0.00%)  0 0/6 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof. Dr. Nurullah Okumuş
Organization: Afyonkarahisar Health Sciences University
Phone: +90 532 4372406
EMail: drnuri@hotmail.com
Layout table for additonal information
Responsible Party: Nurullah Okumuş, Afyonkarahisar Health Sciences University
ClinicalTrials.gov Identifier: NCT04646109    
Other Study ID Numbers: IVMC_03
First Submitted: November 15, 2020
First Posted: November 27, 2020
Results First Submitted: December 3, 2020
Results First Posted: January 27, 2021
Last Update Posted: January 27, 2021