Clinical trial NCT04422561
Conditions: COVID
Sponsor: Zagazig University
Start date: 2020-05-31; Completion date: 2020-07-27
Enrollment: 340 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
asymptomatic family close contact of confirmed COVID -19 patient will receive prophylactic ivermectin and will be followed up for 14 days for any symptoms \& diagnosis of COVID -19

Detailed description:

Arms: arm 1: Contacts who will receive prophylactic ivermectin arm 2: Contacts who will be only observed without prophylaxis
Interventions: intervention 1: Ivermectin Tablets
Intervention descriptions: intervention 1: two doses 72 hours apart

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
Official Title  
 
Use of Ivermectin as a Prophylactic Option in Asymptomatic Family 
Close Contacts with Patients of COVID-19 
 
 
NCT number: 04422561 
 
 
Document date : 31-5-2020 
 


 


  
  لجنة مراجعة اخالقيات البحث العلمىIRB
e-mail :  IRB_123@yahoo.com
 
 
 
  
  
 
CONFLICT OF INTEREST DISCLOSURE 
STATMENT
 
 
IRB#: --------------------------------------------------------------------------------
 
 
Principal Investigator: ): Prof /Waheed Shouman
 
Title of Protocol: Use of Ivermectin as a prophylactic option in 
asymptomatic family close contacts for patients with COVID-19 
 
 
Each author must indicate below that either (a) no financial conflict of interest exists with any 
commercial entity whose products are described, reviewed, evaluated or compared in the 
research proposal, except for that disclosed under ―Acknowledgements‖ or (b) a potential 
conflict of interest exists with one or more commercial entities whose products are described, 
reviewed, evaluated or compared in the research proposal through the existence of one or 
more of the following relationships: the author is a full or part-time employee of a company; 
has an existing or optional equity interest in a company; owns or partly owns patents licensed 
to a company; has an ongoing retainer relationship (consultant ship, speaker, etc.) with a 
company for which he/she receives financial remuneration; or has received financial 
compensation for this publication or for the work involved in this publication. 
 
I agree with the preceding conditions and provide the appropriate signatures and 
information below accordingly (please photocopy this form and attach additional sheets as need 
be with appropriate information and signatures affixed): 
 
PI Name:Prof Waheed Shouman
 
-----27-5-2020 -----------------Date:           Signature:                             Conflict of Interest: NO 
                              
 
  Co-investigator Name:-   
 
Name 
 
Conflict 
 
Signature 
 
Ramadan M Nafae
 
 
 
Mostafa Ragab
 
 
 
Ashraf Sileem 
 
 
 
ZU- IRB #:
   
 نموذج4
 


  
  لجنة مراجعة اخالقيات البحث العلمىIRB
e-mail :  IRB_123@yahoo.com
 
 
Lamiaa Gaber 
 
 
 
Dalia Anas
 
 
 
Saad Rabae Samra
 
 
 
Mohamed elshabrawy
 
 
 
Abdelmonem Awad Hegazy
 
 
 
Tarek H al_Mahrouky
 
 
 
Ahmad Said 
 
 
 
Ahmad Abbas 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


  
  لجنة مراجعة اخالقيات البحث العلمىIRB
e-mail :  IRB_123@yahoo.com
 
 
 
 
Title: Use of Ivermectin as a prophylactic option in asymptomatic family 
close contacts for patients with COVID-19. 
 
 
Researcher: Waheed M Shouman
 
Professor of Chest Medicine
 
Zagazig University 
 
Egypt
 
Zip: 44519
 
shouman66@yahoo.com
Email: 
 
Tel. +201114812048
 
 
Introduction: 
 
The 1st cases of COVID-19 were reported by the Chinese officials to the 
WHO by 31 December 2019. Worldwide, the total cases by 23 April 
2020 are 2 ,544 ,792 confirmed cases and 175 694 deaths [1]. No 
consensus on a certain drug therapy for COVID-19 infection. A lot of 
drugs are under trial or empirically included in treatment protocols for 
COVID-19. Drug re-purposing is the most widely used method for rapid 
response in the face of this epidemic. Trials to invent denovo medicines 
may not be the perfect rationale, while the death and infection toll is on 
the rise hourly.
 


  
  لجنة مراجعة اخالقيات البحث العلمىIRB
e-mail :  IRB_123@yahoo.com
 
 
One of these previously FDA approved drugs is Ivermectin. 
Ivermectin is FDA-approved drug for Onchocerca volvulus and 
Lymphatic Filariasis [2]. It is known to have wide-spectrum antiviral 
activity against number of viruses under in vitro condition. [3-6] 
Ivermectin has been shown to inhibit the nuclear import of host and viral 
proteins. It has been demonstrated to limit infection by some RNA 
viruses including influenza, dengue and West Nile viruses. Ivermectin 
has similarly been shown to be effective against the DNA virus 
pseudorabies virus (PRV) both in vitro and in vivo. In an in vitro study, 
ivermectin was found to be an inhibitor of the SARS-CoV-2, with a 
single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-
2 able to effect ~5000-fold reduction in viral RNA at 48 h. [7,8] 
 
Rationale
 
Previous studies demonstrated the antiviral role of Ivermectin and 
preliminary results from recent experimental reports highlighted an in 
vitro capability of withholding SARS-CoV-2 replication  
 
Research question
 
 Is oral Ivermectin can prevent symptomatic COVI-19 infection in family 
close contacts with patients diagnosed as having the disease by RT-PCR
 
Hypothesis
 
Ivermectin has an antiviral effect and may be effective in preventing 
development of symptomatic infection in family close contacts with 
patients having COVID-19
 
Aim 
 


  
  لجنة مراجعة اخالقيات البحث العلمىIRB
e-mail :  IRB_123@yahoo.com
 
 
To study oral Ivermectin as a prophylactic treatment in family 
close contacts with COVID-19 patients in the form of 
development of symptoms
 
Objectives
 
To study the effect of oral Ivermectin as a prophylactic option in contacts 
with COVID-19 patients 
 
Individuals:
 
Adult family close contacts to COVID-19 positive patients diagnosed by 
RT-PCR. 
 
Materials and Methods:
 
Study Design interventional study
 
Sample Size: Family close contacts to 50 patients diagnosed as having 
COVID-19 by RT-PCR
 
Location: Isolation facilities/Zagazig University Hospitals
 
Inclusion: Age more than 16 years, Asymptomatic household close 
contacts
 
Exclusion: people previously treated for COVID-19, asymptomatic 
contacts with who have HRCT chest done and suggestive for COVID-19 
infection
 
Intervention : 
 
 All documented asymptomatic family contacts, starting on day of 
diagnosis of their index case will receive Ivermectin according to body 
weight as follows:
 


  
  لجنة مراجعة اخالقيات البحث العلمىIRB
e-mail :  IRB_123@yahoo.com
 
 
40-60 kg : 15 mg
 
60 -80 kg :18 mg
 
> 80 kg : 24 mg 
 
This will be given as one dose at day one (diagnosis day), repeated once 
at day 3
 
In literature, individuals can receive 600mcg per Kg of ivermectin daily 
for 3 days without side effects (9,10)
 
Follow up: 
 
1-These asymptomatic persons will be followed up for 2 weeks after the 
diagnosis of index case for: 
 
Symptoms development, 
 
Radiological evaluation if symptoms developed (HRCT chest)
 
Swabs for SARS-2 Virus if symptomatic
 
Recording possible side effects during treatment: eg sleepiness and 
fatigue
 
References:
 
https://www.who.int/docs/default-source/coronaviruse/situation-
reports/20200423-sitrep-94-covid-19.pdf?sfvrsn=b8304bf0_4.
 
Accessed 23-4-2020.
 
Aránzazu González Canga, Ana M. Sahagún Prieto, M. José Diez 
Liébana, Nélida Fernández Martínez, Matilde Sierra Vega, Juan J. 
García Vieitez. The Pharmacokinetics and Interactions of Ivermectin 
in Humans—A Mini-review. AAPS J. 2008 Mar; 10(1): 42–46
 


  
  لجنة مراجعة اخالقيات البحث العلمىIRB
e-mail :  IRB_123@yahoo.com
 
 
Mastrangelo E, Pezzullo M, De Burghgraeve T, et al. 
Ivermectin is a potent inhibitor of flavivirus replication 
specifically targeting NS3 helicase activity: new prospects for an old 
drug. J Antimicrob Chemother. 2012; 67(8):1884-1894. 
 
Götz, V., Magar, L., Dornfeld, D. et al. Influenza A viruses escape from 
MxA restriction  at the expense of efficient nuclear vRNP import. Sci 
Rep 6, 23138 (2016).
 
 Lundberg L, Pinkham C, Baer A, Amaya M, Narayanan A, Wagstaff 
KM, Jans DA,Kehn-Hall K. Nuclear import and export inhibitors 
alter capsid protein distribution in mammalian cells and reduce 
Venezuelan Equine Encephalitis Virus replication, Antiviral Research 
2013; 100(3): 662-672.
 
Azeem S, Ashraf M, Rasheed MA, Anjum AA, Hameed R. Evaluation of 
cytotoxicity and antiviral activity of ivermectin against Newcastle 
disease virus. Pak J Pharm Sci. 2015; 28(2):597-602.
 
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA 
approved drug ivermectin inhibits the replication of SARS-CoV-2 in 
vitro. Antiviral Research 2020. 
 
Ketkar H, Yang L, Wormser GP, Wang P. Lack of efficacy of ivermectin 
for prevention of a lethal Zika virus infection in a murine system. 
Diagnostic Microbiology and Infectious Disease 2019; 95(1): 38-40. 
 
Smit MR, Ochomo EO,Waterhouse D et al Pharmacokinetics-
pharmacodynamics of high-dose ivermectin with dihydroartemisinin-
piperaquine on mosquitocidal activity and QT-prolongation 
(IVERMAL). Clin Pharmacol Ther 2019; 105: 388–401
 


  
  لجنة مراجعة اخالقيات البحث العلمىIRB
e-mail :  IRB_123@yahoo.com
 
 
Navarro M, Camprubí D, Requena-Méndez A, et al. Safety of 
high-dose ivermectin: a systematic review and meta-
analysis. J Antimicrob Chemother 2020;75:827-34. 
 
 


Consort Flow diagram of Ivermectin prophylaxis trial 
Assessed for eligibility (n= 379 contacts 
of 93 confirmed index cases) 
Excluded (n= 39 contacts and 10 
confirmed index cases) 
♦   Not meeting inclusion criteria (n=39  ) 
♦   Declined to participate (n= 0  ) 
♦   Other reasons (n= 0 ) 
Analysed (n=203 contacts of 52 confirmed index 
cases)  
♦ Excluded from analysis (give reasons) (n=0) 
Lost to follow-up (n= 25 contacts of 5 
confirmed index cases) 
Discontinued intervention (failure to follow up 
contacts for 14 days) (n= 25) 
Allocated to intervention Ivermectin arm  
(n= 228 of 57 confirmed index cases) 
♦ Received allocated intervention (n= 228  ) 
♦ Did not receive allocated intervention (give 
reasons) (n= 0 ) 
Lost to follow-up (n= 11 contacts of 2 
confirmed index cases) 
Discontinued intervention (failure to follow up 
contacts for 14 days) (n=11) 
Allocated to intervention No intervention arm 
(n= 112 of 26 confirmed index cases)  
♦ Received allocated intervention (n= 112  ) 
♦ Did not receive allocated intervention (give 
reasons) (n= 0 ) 
Analysed (n=101 contacts of 24 confirmed 
index cases)  
♦ Excluded from analysis (give reasons) (n= 0) 
Allocation 
Analysis 
Follow-Up 
Randomized (n= 340 contacts of 83 confirmed index cases) 
Enrollment 


 
Statistical analysis  
All data were collected, tabulated and statistically analyzed using SPSS 22.0 
for windows (IBM Inc., Chicago, IL, USA) and MedCalc 13 for windows 
(MedCalc Software Bvba, Ostend, Belgium). Continuous Quantitative 
variables were expressed as the mean ± SD & median (range), and 
categorical qualitative variables were expressed as absolute frequencies 
(number) & relative frequencies (percentage). Continuous data were 
checked for normality by using Shapiro Walk test. Mann-Whitney U test 
was used to compare between two groups of non-normally distributed data. 
Categorical data were compared using Chi-square test or Fisher's exact test 
when appropriate. Relative risk and its 95%Confidence interval (CI) was 
calculated to estimate risk of COVID-19 infection in addition forest plot was 
plotted. Univariate and multivariate binary logistic regression were built to 
find predictors for COVID-19 protection. All tests were two sided. p-value < 
0.05 was considered statistically significant.  
 
 
 
 
 
 
 


Results 
As regard index cases, there were 9 (11.8%) mild , 44 (57.9%) moderate and 
23 (30.3%) severe cases. In the ivermectin group, there were 8 (53.3%) mild 
, 6 (40%) moderate and 1 (6.7%) severe cases. While in the no-intervention 
group, there were 31 (52.5) mild, 21 (35.6%) moderate and 7 (11.9%) cases.  
 
 
 
Figure (1): Scatter plot shows relationship between contact time in days and 
number of contacts that developed COVID-19; dashed line represent best 
fitted line (quadratic model). 


There was insignificant linear correlation between contact time in days and 
number of contact that developed COVID-19. The appropriate forecasting 
for number of contact that developed COVID-19 based upon contact time in 
days was quadratic model. 
 
Figure (2): Box plot shows relationship between isolation and number of 
contacts that developed COVID-19. 
There was insignificant difference between index cases isolated at hospital 
and index cases isolated at home regarding number of contact that developed 
COVID-19 where mean number of contact that developed COVID-19 (±SD) 
was 2.14 (±1.35) versus 2.07 (± 2.26) respectively (p-value=0.208) 
 


Table (1): Comparison between Ivermectin arm and non-intervention 
arm regarding basic characteristics.  
Basic characteristics 
Ivermectin arm 
(N=203) 
 
Non-intervention arm 
(N=101) 
Test 
p-
value 
No. 
% 
No. 
% 
Gender 
 
 
 
 
 
 
 
Male 
106 
52.2% 
 
50 
49.5% 
0.199a 
0.656 
Female 
97 
47.8% 
 
51 
50.5% 
Age (years) 
 
 
 
 
 
Mean ± SD 
39.75 ± 14.93 
 
37.69 ± 16.95 
-
1.357
b 
0.175 
Median (Range) 
38 (16 – 94) 
 
35 (16 – 78) 
Any comorbidity 
 
 
 
 
 
 
 
Absent 
156 
76.8% 
 
75 
74.3% 
0.248a 
0.619 
Present 
47 
23.2% 
 
26 
25.7% 
a: Chi-square test; b: Mann Whitney U test; p< 0.05 is significant. 
Table (1) shows that there was no significant difference between both arms 
as regard gender, age or comorbidities. The median (range) age for both 
groups was 38 (16-94) and 35 (16-78) years respectively. 
The most common comorbidities were; hypertension in 16 (7.9%) and 13 
(12.9%), DM in 13 (6.4%) and 10 (9.9%), bronchial asthma in 7 (3.4%) and 
2 (2%), ischemic heart disease in 6 (3%) and 1 (1%),  hypothyroidism in 5 
(2.5%) and 1 (1%), chronic kidney disease in 2 (1%) and 1 (1%),  liver 


cirrhosis in 1 (0.5%) and 1 (1%), cardiomyopathy in 2 (1%)  and 0% in both 
ivermectin and no-intervention group respectively. 
 
Table (2): Comparison between Ivermectin arm and non-intervention 
arm regarding outcome. 
Outcome 
Ivermectin arm 
(N=203) 
 
Non-intervention arm 
(N=101) 
Test 
p-value 
No. 
% 
No. 
% 
Symptoms 
 
 
 
 
 
 
 
Absent 
188 
92.6% 
 
42 
41.6% 
95.351
a 
<0.001 
Present 
15 
7.4% 
 
59 
58.4% 
Days until symptoms 
 
 
 
 
 
Mean ± SD 
3 ± 1.30 
 
4.13 ± 1.78 
-
2.391b 
0.017 
Median (Range) 
2 (2 – 6) 
 
4 (2 – 10) 
2 days 
8 
53.3% 
 
12 
20.3% 
10.150
a 
0.118 
3 days 
2 
13.3% 
 
13 
22% 
4 days 
3 
20% 
 
11 
18.6% 
5 days 
1 
6.7% 
 
13 
22% 
6 days 
1 
6.7% 
 
1 
1.7% 
7 days 
0 
0% 
 
8 
13.6% 
10 days 
0 
0% 
 
1 
1.7% 


CT suspect 
 
 
 
 
 
 
 
Negative 
7 
50% 
 
30 
51.7% 
0.013a 
 
>0.05 
Positive 
7 
50% 
 
28 
47.3% 
CBC suspect 
 
 
 
 
 
 
 
Negative 
2 
14.3% 
 
5 
8.6% 
0.412 a 
>0.05 
Positive 
12 
85.7% 
 
53 
91.4% 
Protection rate 
 
 
 
 
 
 
 
No protection 
15 
7.4% 
 
59 
58.4% 
95.351
a 
<0.001 
Protection 
188 
92.6% 
 
42 
41.6% 
a: Chi-square test; b: Mann Whitney U test; p< 0.05 is significant. 
Table (2) shows that 15 contacts (7.4%) developed COVID-19 in the 
ivermectin arm compared to 59 (58.4%) in the no-intervention arm, all of 
them were symptomatic, according to the study protocol . The difference 
was highly significant (p<0.001). The median (range) days for developing 
the disease was 2 (2-6) in ivermectin group compared and 4 (2-10) in the no-
intervention group, the difference was significant (p<0.017). Ten contacts 
(66.6%) developed symptoms in 1st 3 days in ivermectin group, and none 
developed it after 6 days. In the no-intervention arm, 25 (42.3%) developed 
symptoms in the 1st 3 days and continued to the 10 days.  
HRCT of the chest was performed in 14 out 15 contacts and in 58 of the 59 
contacts who developed symptoms in ivermectin and no-intervention 
groups, respectively. The missed one case in each arm had symptoms and 
positive RT-PCR without other investigations. Chest HRCT was positive for 


COVID-19 in 7 (50%) and 28 (48.3%) in ivermectin and no-intervention 
groups, respectively.  
Complete blood count was performed also in 14 and 58 contacts who 
developed symptoms in ivermectin and no-intervention groups respectively. 
Positive criteria in CBC was present in 12 (85.7%) and 53 (91.4%) in 
ivermectin and no-intervention groups respectively. 
 
Table (3): Comparison between Ivermectin arm and non-intervention 
arm regarding protection rate stratified by basic characteristics. 
 
 
Protection rate 
Testa 
p-value 
Ivermectin  
arm  
Non-intervention 
arm 
All patients 
 
92.6% 
41.6% 
------ 
------ 
Index 
case 
severity 
Mild 
 
92.9% 
35% 
11.381 
0.001 
Moderate 
95.6% 
55.8% 
42.666 
<0.001 
Severe 
85.2% 
28.9% 
29.928 
<0.001 
Age 
≤60 
93.8% 
41.3% 
91.514 
<0.001 
>60 
84% 
44.4% 
5.320 
0.034 
Gender 
Male 
94.3% 
42% 
53.482 
<0.001 
Female 
90.7% 
41.2% 
42.278 
<0.001 
Any 
comorbidity 
No 
95.5% 
45.3% 
77.474 
<0.001 
Yes 
83% 
30.8% 
19.899 
<0.001 


DM 
No 
94.7% 
42.9% 
96.308 
<0.001 
Yes 
61.5% 
30% 
2.253 
0.214 
HTN 
No 
93% 
44.3% 
81.372 
<0.001 
Yes 
87.5% 
23.1% 
12.272 
<0.001 
a: Chi-square test; p< 0.05 is significant. 
Table (3) shows that 7.4% contacts developed diseases in ivermectin group 
while they were 58.4% in no-intervention group. Contacts tend to be 
infected when the index case was severe; 14.8% and 71.1% in both groups, 
respectively. The protection rate for ivermectin was more prominent in 
contacts less than 60 years old (6.2% infected compared to 58.7% if no 
intervention) , but still effective in elder than 60 years (16% infected 
compared to 55.6% if no intervention). 
.  
Table (4): Predictors for COVID-19 protection. 
 
Univariate Model 
 
Multivariate Model 
OR (95%CI) 
p-value 
OR (95%CI) 
p-value 
Arm 
 
 
 
 
 
Ivermectin 
12.533 (7.408-21.205) 
<0.001 
 
11.445 (4.444-29.475) 
<0.001 
Non-intervention 
Reference 
 
 
 
 
Index case severity 
 
<0.001 
 
 
0.018 
Mild 
1.429 (0.722-2.828) 
0.306 
 
1.257 (0.486-3.247) 
0.637 
Moderate 
6.120 (4.010-9.341) 
<0.001 
 
2.816 (1.355-5.851) 
0.006 


Severe 
Reference 
 
 
 
 
Age 
 
 
 
 
 
Age≤60 years 
3.154 (2.386-4.169) 
<0.001 
 
0.254 (0.101-0.639) 
0.004 
Age>60 years 
Reference 
 
 
 
 
Gender 
 
 
 
 
 
Male 
3.457 (2.373-5.036) 
<0.001 
 
0.836 (0.437-1.600) 
0.588 
Female 
Reference 
 
 
 
 
Any comorbidity 
 
 
 
 
 
Absent 
3.812 (2.774-5.239) 
<0.001 
 
2.222 (0.967-5.108) 
0.060 
Present 
Reference 
 
 
 
 
OR: Odds Ratio; 95%CI: 95%Confidence Interval. 
Table (5) shows that ivermectin have very highly significant role in the 
protection of SARS-CoV-2 infection. . It has an OR of 12.533 and 11.445 
when compared to no intervention in both univariate and multivariate 
models, respectively.  Ivermectin protection was not affected by gender or 
comorbidities in multivariate model. 
As regard ivermectin side effects, they were reported in 11 (5.4%) contacts. 
These were; diarrhea (1.5%), nausea (1%), fatigue (1%), sleepiness (0.5%), 
abdominal pain (0.5%), heart burn (0.5%), tingling and numbness (0.5%) 
and lastly burning sensation (0.5%)