Clinical trial NCT04673214
Conditions: Covid19
Sponsor: Gilberto Cruz Arteaga
Start date: 2020-12-16; Completion date: 2021-02-25
Enrollment: 114 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The present study is designed for patients with mild COVID-19 phase, to demonstrate if there is a modification in the clinical evolution greater than or equal to 25% in their symptoms, implemented in two groups of patients under an early intervention treatment, a group ( A) will receive Azithromycin / Ivermectin / Ribaroxaban / Paracetamol and another group (B) will receive Azithromycin / Ribaroxaban / Paracetamol followed for 14 days followed by video call

Detailed description:
Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potential fatal disease generating a global public health problem. Person-to-person transmission of COVID-19 infection led to the isolation of patients who subsequently received a variety of treatments. Ivermectin treatment for safety is approved for human use by the FDA in parasitic and skin infections. Studies report the therapeutic safety of Ivermectin in humans with COVID-19, describing a 6.1-fold decrease in lethality compared to patients who did not use Ivermectin (1.4 vs. 8.5%, p \<0.0001). In this sense, the WHO and PAHO encourage the use of unproven therapies in the context of a randomized clinical trial (RCT). Anticoagulants have reported up to 20% in the reduction of mortality (heparin), Ribaroxaban is effective with the inhibition of PAR1 / PAR2 / PAR4 receptors through the blocking of Factor Xa and the formation of thrombin, having anti-inflammatory effects, decreasing arteriosclerosis and platelet aggregation. There is a Telemedicine working method implemented by the OOAD of the North Federal District, which detects early signs and symptoms of possible complications and offers an early intervention treatment policy for first-level care beneficiaries. Under this method, a quasi-experimental study showed that there is a modification in the frequency of recovered patients of 80-90% in patients diagnosed with COVID-19 after an early intervention treatment with paracetamol, Ivermectin, Azithromycin, Ribaroxaban in patients with COVID -19 from UMF 13 during the period of July-August 2020. Therefore, it is necessary to carry out a randomized clinical trial to confirm this assertion.

Objective: To evaluate the percentage of patients with a diagnosis of COVID-19 who modify their clinical evolution under a comparative treatment of early intervention in beneficiaries of the U.M.F 13 and U.M.F 20 of the I.M.S.S., during the period of December 2020-January 2021.

Material and Methods: A randomized, single-blind, prospective, longitudinal and open experimental study in 62 patients with COVID-19 from UMF No. 13 and No. 20 from November to December 2020. Including 31 patients in group A (Azithromycin / Ivermectin / Ribaroxaban / Paracetamol) and 31 patients in group B (Azithromycin / Ribaroxaban / Paracetamol). With inclusion criteria over 18 years of age, have type 2 diabetes mellitus, Systemic Arterial Hypertension, Obesity or overweight, PCR confirmation of COVID-19. For the video call, the Family Medicine Units have Electronic Equipment Installation for Internet use. Exclusion criteria are patients with severe COVID-19 (they deserve immediate referral to second level of care, hospital). Elimination criteria are Prior informed consent, medication is given randomly to a COVID-19 patient, a follow-up video call will be made at home for 14 days, recording sex, age, education, date of disease onset, taking laboratories (hematic biometry, C-reactive protein, D-dimer, Ferritin, prothrombin time, thromboplastin time, lactic dehydrogenase) taken at the onset of the disease, taking as an outcome variable the modification of the clinical course (clinical symptoms such as headache, cough, fever, conjunctivitis , myalgias, arthralgias, rhinorrhea, odynophagia, anosmia, chest pain, dyspnea) when granting treatment in groups A and B.. Statistical differences will be evaluated using the Mann-Whitney U test with a power of 90% and a type I error rate of 1% for the variable of modification of the clinical course in treatment groups A and B. analysis will be performed in SPSS version 21.

Arms: arm 1: Paracetamol 500 mg orally 1 tablet every 8 hours for 3 days in case of fever equal to or greater than 38.3 ° C, Azithromycin 500 mg tablets will take 1 tablet single dose the first day and then half tablet (250 mg) orally every 24 for 4 days, Ivermectin tablets of 200mcg which will be calculated according to your weight and dose, will be every 24 hours for 2 days and Rivaroxaban tablets of 10 mg will take 1 every 24 hours for 10 days arm 2: Paracetamol 500 mg orally 1 tablet every 8 hours for 3 days in case of fever equal to or greater than 38.3 ° C, Azithromycin 500 mg tablets will take 1 tablet single dose the first day and then half a tablet orally every 24 for 4 days and Rivaroxaban 10 mg tablets will take 1 every 24 hours for 10 days.
Interventions: intervention 1: Azithromycin / Ivermectin / Ribaroxaban / Paracetamol intervention 2: Azithromycin / Ribaroxaban / Paracetamol
Intervention descriptions: intervention 1: In the patient with the presence of COVID-19 confirmed by the PCR-COVID-19 positive test, the drug is randomly assigned to belong to group A of Azithromycin / Ivermectin / Ribaroxaban / Paracetamol to be followed for 14 days by video call (approximately 15 to 20 min per day) to the patient and the presence or absence of clinical symptoms, adverse reactions being recorded daily intervention 2: In the patient with the presence of COVID-19 confirmed by the PCR-COVID-19 positive test, the drug is randomly assigned to belong to group B of Azithromycin / Ribaroxaban / Paracetamol, to be followed for 14 days by video call (approximately 15 to 20 min per day) to the patient and the presence or absence of clinical symptoms, adverse reactions being recorded daily

Protocol documents:
Prot_SAP_000.pdf: 
1 
 
 
 
MEXICAN SOCIAL SECURITY INSTITUTE 
FAMILY MEDICINE UNIT No. 20 VALLEJO 
 
 
 
 
1. TITLE OF THE INVESTIGATION PROTOCOL  
 
 
“PRONOSTIC MODIFICATION IN PATIENTS WITH COVID-19 UNDER EARLY INTERVENTION 
TREATMENT IN U.M.F 13 AND U.M.F 20”.   
 
 
 
 
IDENTIFIERS: NCT04673214 
 
 
 
DOCUMENT DATE: DECEMBER 11, 2020 
 
 
 
 
 
 


2 
 
 
 
 
 
 
INDEX 
 
 
 
1. Title    ………………………………………………………………………………...…………………………………………… 
1 
2. Summary …. …………………………………………............................................................................ 
3 
3. Theoretical Framework …………………………………………………………...…………………………………..... 
5 
4. Justification …..…………………………………………………………………..…………………………………………… 
28 
5. Statement of the Problem ………….…………........................................................................... 
29 
6. Objective .. ………….………………………………………………………………………………………………………..… 31 
7. Working hypothesis ……………..…………………………………………………………………………………………. 32 
8. Material and methods …………………………………………………………….......................................... 33 
9. Ethical  Aspects…………………………………………………………………………………………………………………   45 
10. Physical and  Financial Resources…………………………………………………………………………………….. 
47 
11. Timeline of protocol activities………………………………………………………………………………………….. 
48 
 
12. Bibliographic references .. ……….……………………………………………………………………………………… 
50 
     13. Annexes........................................................................................................................... 
57 


3 
 
2. SUMMARY 
 
“EVALUATION OF PROGNOSTIC MODIFICATION IN COVID-19 PATIENTS IN EARLY 
INTERVENTION TREATMENT”.     
 
 
Introduction: Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the 
causative agent of a potential fatal disease generating a global public health problem. 
Person-to-person transmission of COVID-19 infection led to the isolation of patients who 
subsequently received a variety of treatments. Ivermectin treatment in relation to its safety 
is approved for human use by the FDA in parasitic and skin infections. Studies report the 
therapeutic safety of Ivermectin in humans with COVID-19, describing a 6.1-fold decrease 
in lethality compared to patients who did not use Ivermectin (1.4 vs. 8.5%, p <0.0001). In 
this sense, the WHO and PAHO encourage the use of unproven therapies in the context of 
a randomized clinical trial (RCT). Anticoagulants have reported up to 20% in the reduction 
of mortality (heparin), Ribaroxaban is effective with the inhibition of PAR1 / PAR2 / PAR4 
receptors through the blocking of Factor Xa and the formation of thrombin, having anti-
inflammatory effects, decreasing arteriosclerosis and platelet aggregation. There is a 
Telemedicine working method implemented by the OOAD of the Northern Federal District, 
which detects early signs and symptoms of possible complications and offers an early 
intervention treatment policy for first-level care beneficiaries. Under this method, a quasi-
experimental study that shows that there is a modification in the frequency of recovered 
patients of 80 -90% in patients diagnosed with COVID-19 after an early intervention 
treatment with paracetamol, Ivermectin, Azithromycin, Ribaroxaban in patients with COVID 
-19 from UMF 13 during the period of July-August 2020. Therefore, it is necessary to carry 
out a randomized clinical trial to confirm this assertion. 
Objective: To evaluate the percentage of patients with a diagnosis of COVID-19 who modify 
their clinical evolution under a comparative treatment of early intervention in beneficiaries 
of the U.M.F 13 and U.M.F 20 of the I.M.S.S., during the period of December 2020- February  
2021. 
Material and Methods: A randomized, single-blind, prospective, longitudinal and open 
experimental study in 62 patients with COVID-19 from UMF No. 13 and No. 20 from 
November to December 2020. Including 31 patients in group A (Azithromycin / Ivermectin 
/ Ribaroxaban / Paracetamol) and 31 patients in group B (Azithromycin / Ribaroxaban / 
Paracetamol). With inclusion criteria over 18 years of age, have type 2 diabetes mellitus, 
Systemic Arterial Hypertension, Obesity or overweight, PCR confirmation of COVID-19. For 


4 
 
the video call, the Family Medicine Units have Installation of Electronic Equipment for 
Internet use. Exclusion criteria are patients with severe COVID-19 (they deserve immediate 
referral to second level of care, hospital). Elimination criteria are Prior informed consent, 
medication is given randomly to a COVID-19 patient, a follow-up video call will be made at 
home for 14 days, recording sex, age, schooling, date of disease onset, taking laboratories 
(hematic biometry, C-reactive protein, D-dimer, Ferritin, prothrombin time, thromboplastin 
time, lactic dehydrogenase) taken at the onset of the disease, taking as an outcome variable 
the modification of the clinical course (clinical symptoms such as headache, cough, fever, 
conjunctivitis , myalgia, arthralgia, rhinorrhea, odynophagia, anosmia, chest pain, dyspnea) 
when giving treatment in groups A and B.. Statistical differences will be evaluated using 
Pearson's Chi-square test or Fisher's exact test, with a power of 90% and a type I error rate 
of 1% for the variable of modification of the clinical evolution in the groups of treatment A 
and B. The analyzes will be carried out in SPSS version 21. It is a feasible study since it has 
the infrastructure and supplies as well as the experience of the researchers for the 
management of COVID-19 patients, being an associate researcher Hematologist to 
contribute his experience in the surveillance of these patients. Estimated time for 
completion: December 2020- February 2021. 
Keywords: COVID-19; outpatient follow-up telemedicine; early intervention treatment.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


5 
 
3.  Theoretical Framework  
 
            In December  2019, the World Health Organization (WHO)was reported to detect 
pneumoniaof unknown causes in Wuhan Province, China. On 13 January 2020, Thailand's 
Ministry of Public Health reported the first imported case of the new laboratory-confirmed 
coronavirus 2019-nCov, the first case being confirmed outside China. This outbreak was 
declared on January 30, 2020 as a public healthemergency of internationalinterest. On 11 
February 2020, WHO announced the name for the disease caused by the new coronavirus: 
COVID-19. On the same day, the International Committee on Virus Taxonomy announced 
SARS-CoV-2 as the name of the nuevo virus that causes COVID-19. On 11 March 2020, WHO 
reportedCOVID-19 as a pandemic.   By March 13, 2020,the s 5,000 deaths   had already been 
achieved for this cause, and Europe was   subsequently the epicenter of a greater number 
of cases and deaths than the rest of the world, not counting China. 1 
 
            On February 26, the first case of coronavirus was reported in Latin America, 
specifically in Sao Paulo, confirmed by the Brazilian Ministry of Health as a male with a 
history of travel to Lombardy, Italy.   On February 28, the first case was confirmed in Mexico 
City, in a 35-year-old male who also had a history of traveling to Italy. 2 
 
         With respect to the Americas region,the United States of America contributes the 
majority ofcases and deaths (89% and 90% respectively), distributed in all  50 states. In 
North America, a4.75% chance of lethality is reported. 3 
 
4.1 Epidemiology 
 
At the beginning of May, there were 1,035,353 positive patients with Covid-19 in the 
United States of America; value that doubled in less than two months. And as of October 
22, 2020, this count amounted to 8,184,788; which translates as a 690% increase in cases 
compared to the existing ones at the beginning of May. WHO currently estimates that 
around 60,155 new cases confirmed with Covid-19 occur each day in thiscountry.   4 
Similarly, the exponential increase in mortality was also reflected by the number of 
62,637 deaths at the start of May and from 219,497 to 22 October; suggesting that on 
average, 896 people died each day from Covid-19 in less than six months.  4 
These epidemiological figures contrast significantly with those of the People's 
Republic of China, where active cases declined significantly from the second half of 
February. So from May (at which point 84,391 patients were infected) to October 2020, only 
7,197 new confirmed cases positive for the virus were reported, an average of 23 to 41 per 
day. It should be noted that the relationship between the incidence of cases and deaths has 


6 
 
also been proportional. In less than six months, only 103 patients have died of Covid-19, 
which would be assessed as 0.58% of deaths per day as of May 4 
           According to WHO, the median age in China was 51 years, with most cases between 
the ages of 30 and 69. Regarding sex there is a slight predominance of the male sex with 
51%. 5 
 
           As of May 06, 2020, 3, 588,773 confirmed cases and 247,503 deaths have been 
reported worldwide. The overall fatality rate is 6.9%. In Mexico, 27,634 confirmed cases, 
17,553 suspected cases and 2,704 deaths have been reported. 6 
 
           Men have been slightly more affected by 58.48% compared to women with 41.52%. 
59.34% of patients have received outpatient treatment, while 40.66% have required 
hospitalization. 7 
 
            Speaking specifically of Mexico, according to data obtained by the Ministry of Health, 
the percentage of confirmed patients positive with SARS-CoV-2, has grown alarmingly as of 
May 2020. At the beginning of that month, the number of infected was limited to 23,471 
patients. From that time until the beginning of August, the figures released to 456,100 
active cases. 8 
 
           During the month of August, a second spike in contagion gradually resulted. With this, 
847,108 accumulated active cases have been reached until 17 October; equivalent to 
approximately 4,706.5 new infected patients per day in less than six months. In this regard, 
and exclusively throughout October, 748,315 cumulative confirmed cases had been 
identified at the beginning of the month; as of October 17, it was possible to count 847,108 
sick patients, with a 13% increase between the first and second figures so far this month.  8 
 
           As for the suspected cases, a stable number of patients are reported, with a sudden 
and only significant increase at the end of September, maintaining from there, a new and 
relative stability. Thus, the number of suspected patients accumulated amounts to 316,228 
cases. 
           The mortality curve also had unsettling growth from late April to mid-May. In the 
latter, a number of 5,177 deaths were conceptualized; however, this amount multiplied to 
the extent of reaching 86,069 deaths, with an average of 462 deaths per day in the last 6 
months. 8 
 
          In summary, as of October 17, 2020, there are a cumulative total of 847,108 confirmed 
patients, 316,228 suspected cases and 86,069 deaths in ourcountry. 8 


7 
 
 
           The median incubation period is 5-6 days with a range of 1 to 14days. 9 
 
           Transmission is considered to begin 1 to 2 days prior to the onset of symptoms, 
although it is still unknown whether from symptomatic people the intensity of transmission 
is the same as in asymptomatic people. It has been noted that most infected patients have 
a high viral load (up to 104 and 108 copies of genome/ml per nasopharyngeal or saliva 
sample) as measured by RT-PCR. However, patients with mild infection, the peak viral load 
occurs during the first 5-6 days after the onset of symptoms and practically disappears on 
day 10. Although post-day 10 viruses are detected in some patients, the viral load is 100-
1,000 times lower, so low transmission capacity is expected these days. In addition, with 
viral loads below 105 copies there is no growth of the virus in crops. This suggests that, in 
people with mild symptoms, chance of transmitting the infection to others would be very 
low after the first week after the onset of symptoms, even when the virus is still detectable 
by PCR. In people with severe infection the viral load is up to 60 times higher than those of 
milder course and viral excretion may be more durable.  5 
 
           The average time between onset of symptoms and recovery in patients with mild 
illness is approximately 2 weeks and in patients with severe or critical disease is 3 to 6 
weeks. Preliminary data suggest that the time it takes for the severe disease to develop is 1 
week. The time between onset of symptoms and death is between 2 and 8 weeks.  5 
 
             The R0 (basic number of reproduction) in the first months of the epidemic in Wuhan 
China was estimated to be between 2 and 3, subsequently in study reviews this value is 
estimated to be between 1.5 and 6.5. It should be noted that the public health and social 
estating measures imposed have had an impact on the decrease in  this  number. Accurate 
estimate of lethality during an outbreak is complicated as cases are updated daily and 
adjusted. The use of models has estimated lethality between hospitalized cases 14% 
(IC95%), and in the general population between 0.3 and 1%. 5 
 
4. 2 Structure 
 
             The viral particle has a diameter of 60 x 100 nm and appears round or oval. It belongs 
to the group of viruses involved. It has a single-category RNA genome with a positive, non-
segmented sense of 29.9Kb. 
 
              Similar to another β- CoVs, SARS-CoV-2 virion has a nucleocápside composed of 
genomic RNA and phosphorylated nucleocapsid protein (N). The nucleocápside is covered 
by a phospholipid bipa, which in turn has 2 different types of peak proteins: peak 


8 
 
glycoprotein (S), triteric, which exists in all CoVs, and hemaglutinin-esterasse (HE) only 
shared among some CoVs. Membrane protein (M) and wrapping protein (E) are among the 
S proteins in the viral envelope. The SARS-CoV-2 genome has terminal sequences of 5o and 
3o (265 nt on the 5 terminals and 229 nt on the 3 terminal), which is typical of β-CoVs. SarS-
CoV-2 predicted genes S, ORF3a, E, M and N are 3822, 828, 228, 669, and 1260 nt in length, 
respectively.  
 
              Similar to SARS-CoV, SARS-CoV-2 carries a predicted ORF8 gene (366 nt in length) 
located between the M and N ORF genes. 10 
 
 
4.3 Physiopathology 
 
4.3.1 SARS-CoV-2 invasion mechanism in host cells  
 
             SARS-CoV-2 penetrates the cell using angiotensin-converting enzyme 2 (ACE-2), a 
membrane exopeptidase present primarily in the kidney, lungs and heart as a receptor. The 
function of ACE2 is the transformation of Angiotensin I into Angiotensin 1-9 and 
Angiotensine II in Angiotensin 1-7. These end products have vasodilator, antifibrosis, anti-
inflammatory effects and promote natriuresis. They are all effects, therefore, that reduce 
blood pressure, counterregulating the action of Angiotensin II. ACE2 has been linked to 
protection against hypertension, arteriosclerosis and other vascular and pulmonary 
processes. In animal models it has been seen that the absence of ACE2 results in increased 
lung damage in the SDRA and  the overexpression  of ACE2 protects against it. In contrast, 
the angiotensin-converting enzyme (ACE), which transforms Angiotensin I into Angiotensin 
II, promotes the generation of secondary peptides with vasoconstrictor,  pro-inflammatory  
and sodium retention effect, which are related to the physiopathology of high blood 
pressure. Severe cases of COVID-19 have been observed to have very high levels of 
Angiotensin II. And the level of Angiotensin II has been correlated with SARS-CoV-2 viral 
load and lung damage. This imbalance of the renin-angiotensin-aldosterone system could 
be related to the virus's inhibition of ACE2. This same effect was already observed in the 
SARS outbreak in 2003. 11 
 
 
 
 
 
 
 
 


9 
 
4.4 Clinical picture 
 
              The route of transmission between humans is through the secretions of infected 
people, mainly by respiratory droplets of more than 5 microns10,11,which are able to reach 
up to 2 metros away, reaching theSARS-Cov-2in objectas copper, chore, stainless steel and 
plastic surfaces,shown to last4, 24, 48 and 72 hrs when maintained at 21-23oC and with 
40% humidity. On paper it is no longer detected after 3 hrs, wood, ropa or glass up to 1 to 
2 days,  > 4 days in stainless steel, plastic, money banknotes and surgical masks. 12 
   
A three-countryr eporte is present with the following symptoms  and signs in sarS-Cov-2 
patients: 
Fever(87%)12 
Fever(68.7%)12 
Fever13 
Dry cough (67.7%) 
Those (68.1%) 
Dry cough 
 Asthenia (31%) 
Dyspnoea (31%) 
Headache 
Expectoration (33.4%) 
Chills (27%) 
Dyspnea 
Dyspnoea (18.6%) 
Sore throat (24.1%) 
Myalgias or Arthralgias 
Sore throat (13.9%) 
Diarrhea (14%) 
Anorexia (SD) 
Headache (13.6%) 
Vomiting (6%) 
Dizziness (SD) 
Myalgias or arthralgias (14.8%) 
 
Runny nose 
Chills (11.4%) 
 
Conjunctivitis 
Nausea or vomiting (5%) 
 
Chest Pain 
Nasal congestion (4.8%) 
 
 
Diarrhea (3.7%) 
 
 


10 
 
Hemoptisis (0.9%) 
 
 
Conjunctival congestion (0.8%) 
 
 
In China with 55,924 cases 
Spain with 14,011 cases 
Mexico with 29,616 
cases 
SD: No data 
 
            
               The incubation period is 5-6 days, with a range of 1 to 14 days. 97% of symptomatic 
cases develop within 11.5 days after exposure. 12 
 
                Clinical manifestations are not yet clear, as reported symptoms vary are usually 
mild and begin gradually, although severe intakes(dyspnoea, pneumonia) mayoccur. 14  The 
most reported symptoms in Mexico are  fever, dry cough and headache. 13  Wuhan also 
reported other symptoms related toorgans and systems12:  
 
Cardiac 
The disease can occur with related symptoms of heart 
failure or acute myocardial damage, even in the absence 
of fever and respiratory symptoms. 12 
Neurological  
Wuhan reported study with 214 patients of whom 36% 
had 
neurological 
symptoms: 
Dizziness 
(17%), 
Consciousness disturbances (7%), Stroke (2.8%), Vascular 
brain accidents  (2.8%), ataxia (0.5%) 
Otorrinolaringológicos 
The most common reported: facial pain, nasal obstruction, 
anosmia- hyposmia, dysgeusia-hypogeusia. 
Hematologic 
Thrombotic phenomena associated with COVID-19 cases 
that manifest as stroke, cardiac ischemia, sudden death, 
embolism, TVP* 
*TVP (Deep Vein Thrombosis).  
Source: prepared by Scientific-Technical Information. Coronavirus Disease, COVID-1912 


11 
 
 
          It has now been reported that most hospitalized patients have some comobility; high 
blood pressure and diabetes are the most  common. 14  Other comorities, lung problems, 
cancer, immunocompromised people are more likely to have severe pictures.   
 
           Increased D-dime and to a lesser extent increased prothrombin time and 
thrombocytopenia have been considered markers of poorer severity and mortality 
prognosis. 14 
 
          Symptomatology presented  in patients with COVID-19 has shown that real-time 
polymerase chain reaction (RT-qPCR) is the most efficient for  diagnosis  15 
 
4.5 Covid-19 diagnosis 
 
          Clinical diagnosis of COVID-19 is based primarily on epidemiological history, clinical 
manifestations and other auxiliary studies, such as nucleic acid detection, computed 
tomography, IgM/IgG immune identification technology, ELISA and blood culture. 15 
 
          Clinical signs and symptoms of SARS-Cov2-infected patients are atypical, including 
respiratory symptoms such as cough, fever, dyspnoea, andpneumoní to viral. Therefore, 
auxiliary  studies are necessary for confirmation ofinfection with thisvirus. 15 
 
 
4.6 Nucleic acid detection technology 
 
          The two most  commonly used studies of this type are real-time polymerase chain 
reaction (RT-qPCR) and high-performance sequency. The authorized methods for detecting 
the virus is high-performance sequencing and blood virus culture, but the application of the 
first method depends on very high-cost equipment, so RT-qPCR is the most common, 
effective and simple for secretion virusdetectionis respiratory and blood.   15 
 
            Taking into account symptomatology and laboratory studies for their diagnostica 
confirmation in patients withCOVID-19,se have developed   technologies of information and    
communication  (ICTs) to perform clinical follow-up inpatients with cardiovascular diseases 
and in older adults who have succeeded such as the Monitoreo of patients at home,  
Remote Monitoring and Telemedicine/Telehealth.   
 
 
 
 


12 
 
 
3.9      Information and Communication Technologies (TICs) 
 
            Information and Communication Technologies (ICTs)form the set of resources 
necessary to manipulate information and particularly the computers, software and 
networks necessary to convert, store, manage, transmit and find it. They are also used as 
means of learning aid and represent a basic competence that must be disseminated 
regardless of the age of individuals, they offer us great opportunities for all groups of 
society, regardless of how old they are, but it is necessary to know the needs, interests, 
concerns and possible limitations of all citizens to bring them closer to them. 16 
 
               As   Sampadarefers, in his review paper information technologies "has the potential 
to improve the quality, safety and efficiency of health care". So medical staff,  nursesenter 
others can access and use the correct information that the patient needs. 17 
 
               Se has suggested that older adults must take on this change and adapt to these 
new forms of communication; otherwise they will be people who will gradually become 
ingested, which can negatively affect their health, since the use of technology is related to 
a lower manifestation of problems associated with mental health and a higher rate of 
integration and participation. 18 
 
             Educational programmes for Older Adults (AM)  include, among other possibilities, 
the approach of the AM to ICTS, presenting these great interests, given the importance of 
them today and their relevant role, not only as content, but as a means of providing other 
training to recipients. 19 
 
 
3.9.1 Monitoring patients at home.   
 
             Sampada says  that due to staggered health costs in health care, home monitoring 
may be applied particularly in older adult patients with chronic illness. Information  has 
been  recorded of patients with cardiovascular problems through phone calls, making it 
easier for the doctor to use this tool. 17 
 
 
3.9.2 Remote monitoring 
 
             Remote monitoring is the electronic transmissionof health care dataentered directly 
by a patient (or theircare provider) or through a physician to an Electronic Health   
Registration (EHR) deviceor the Personal Health Register of the patient(PHR). A  clinician's 


13 
 
ability to monitorpatient information duringdiagnosis, drug tracking and daily life 
activities(ADL)  measurements, captured remotely, is a key enabler for the managementof 
chronic health problems and management ofnuevas conditions. Remote monitoring may 
include physical measurements  (e.g. weight,  blood pressure, heartrate, pulse oximetry, 
gucosa),   diagnostic measures, drug tracking,  device information(e.g. pumping 
drugs,infusion devices, electronic pillboxes) and  daily life measurement activities (e.g.ADL 
biosensors, pedometers,   sleep activity, etc.) .  17 
 
 
4.9.3 Telemedicine/Telehealth  
 
              Telemedicine is the use of telecommunication technologies to provide health and 
information-related servicesthat support care for thecountry, administrative activities, 
health education, health services and general health information. It is a new method of 
health care that shares and/or exchanges patient-related data and medical opinion 
between amedical speculator and a  doctor in a remote location through 
telecommunication networks. Technology is a means to improve access to care, 
whilereducing  the cost of transportation and increasing the convenience of  patient care. 
Television  - omiciliary care, videoconferencing  and electronic health records are all 
components of Tele health  and use of information technology to provide a service.  17 
 
              Karen Donelan's reports in a transversal study, where 254 people visited  by 
Telemedicine were found for  15 minutes, reported in herpatient experience with virtual 
video visitsby  three different specialists  (psychiatrist, neurologist, cardiologist) answers  > 
90% with "if, definitely  agree"rating, questions focused on whetherthings were explained 
inaneasy way to understand, whetherthe patient's care would be heard and whether he 
feltthat the doctor had spent enough time on the patient when performing the video call. 
20 
 
              With the presence of COVID-19 in Mexico City at  the Mexican Institute of Social 
Security,   a follow-up tool is   developed through the Tecologies of lto Information  and 
Communication (TICs),as sonthe  video calls with the aim of giving follow-up to signs and 
symptomsof COVID-19 and  offer an early intervention treatment policy according to THE 
IMSS COVID-19 patient management scenarios,this is called  the Outpatient Monitoring 
Model.   
 
 
 
 
 


14 
 
4.8 MOutpatient  Tracking  Odelo 
 
              An Outpatient Monitoring Model means a process that during Phase 3 contingency 
in patients with COVID-19 rightholders of the IMSS  is granted by the Unconcentrated 
Administrative Operation Body of the Northern Federal District, to follow up on patients 
diagnosed clinically, confirmed and graduated from COVID-19 in righthabientis first levelof 
care that within the specific objectives is to detect early signs andsymptoms of possible 
complications, andvalue the status of the patient's(possible) co-ntactos,to sesorar al 
paciente ifnecessary,or torgar follow-up appointment in the Unit for revaluation, to offer 
an early intervention treatment policy according to THE IMSS COVID-19 patient 
management scenarios ,  that the drugs be counted according to the availability of the unit, 
in top-level rightholders. A    flowchartis developed to track  patients suspected of COVID-
19, in which COVID-19 (Respiratory Module) patient care facilities are considered, which 
counts the first-level units of care, as well as the staff involved in the management of the 
patient in the respiratory module such as the nurse, the laboratorist, the family doctor and 
cleaning and hygiene personnel, which in turn coordinates with Staff of Heads of Service, 
the area of performance control, nursing and clinical coordination of health education and 
research, this in order to integrate a means of monitoring through the Information and 
Communication Tecologies (TICs),such as phone calls or video calls with the use of computer 
equipment, database, telephone line and internet, necessary to comply with the monitoring 
of the model. (See Table 2, 3 Y 4 ) .  21 
         
                 In relation to the Monitoring of patients with Clinical Phase Leve Covid-19 in the 
First Level Of Care Units of the Northern Delegation, they will be carried out in the triage 
modules, which initiates medical care when the patient is taken vital signs by nursing 
personnel and questioned about alarm data ( dyspnoea, chest pain); in case of presenting 
alarm data you are given a reference to second level of attention. If you do not present 
alarm data, you enter a doctor's office and question compliance with the operational 
definition for COVID-19, the presence of three major symptoms such as headache, cough 
or fever, and at least one of the following minor symptoms such as conjunctivitis, myalgias, 
arthralgias, rhinorrhea, odinophagia, anosmia, chest pain, dyspnoea; when complying with 
the operational definition for COVID-19 the patient will be shown COVID-19 confirmatory 
PCR, if the test is positive the patient is informed about the early intervention treatment 
provided, informing you through informed consent with the specifications set out therein 
(see Annex 1) and also informing the patient that they must have a smartphone (with 
installation of the WhatsApp application) for making video calls. If the patient agrees to sign 
the informed consent, he or she is given a  COVID-19 Information Triptych, the 
pharmacological medicinal product is delivered, upon randomization (see Table 4), and is 
indicated to follow up by video calls that were performed over 14 days, lasting 


15 
 
approximately 15 minutes each video call, with the monitoring and recording of clinical 
symptoms, adverse reactions to the medicines administered and alarm data if sent to a 
second level of care. (See Table 1)


16 
 
Enter respiratory module 
Triage staff (1 
nurses) 
Taking vital 
signs 
 Interrogation aimed 
at COVID-19 
symptoms 
Accepts 
Rightholders with Respiratory 
Symptoms 
Table 1. Monitoring patients with Covid-19 Mild 
Clinical Phase in the North Delegation's First 
Level of Care Unit   
Go into the 
doctor's 
office 
Treat pathology 
Give symptomatic 
treatment, explain 
alarm and isolation data 
at home for 14 days  
Filter staff 
Yes meets operational 
definition 
Does not meet 
operational definition 
1 laboratorist 
Go to office 
It has cell phone equipment the 
patient or primary caregiver 
Doesn't accept 
1. Give triptychs of 
information 
2. Give symptomatic 
treatment 
3. Explain tracking 
through video calls 
for 14 days  
4. Isolation at home 
for 14 days  
-Screening 1 in 10 
(COVID-19 
confirmatory PCR 
Do you present 
alarm data?  
Yes   
No  
Second-level reference 
1 doctor 
Information 
about symptoms 
and warning 
signs for second-
level care 
reference.  
Tracking 
Daily video call for 14 days (recommendation takes rest and movement oxymetry)  
Applicatio
n of tests, 
symptoms 
and signs 
Write down 
Phone Number 
on informed 
consent and 
Not compliant 
for video calling 
tracking 
Ye
s   
No  
Send to Second Level immediately. 
Pharmacological 
intervention by 
the doctor 
confirmed by 
PCR test 


17 
 
 
 
 
Table 2. PERSONNEL INVOLVED IN THE USE OF ICTS 
PERSONAL 
FUNCTIONS 
CLINICAL COORDINATOR OF HEALTH EDUCATION AND RESEARCH 
Coordinate and monitor monitoring of COVID-19 patients 
HEAD OF SERVICE 
Conduct the census of the cases to be followed and will ask the area of 
benefits for patient data (No. Telephone) and designate the staff to 
carry out or who will develop the follow-up 
PERFORMANCE CONTROL 
It will provide the information required by the head of department 
FAMILY DOCTOR AND/OR SOCIAL SERVICE MEDICINE INTERN 
You will make follow-up calls and make a record of it in the census 
made 
Table 3.  MATERIAL USED  
COMPUTER TEAM    
TELEPHONE LINE   
DATABASE   
INTERNET 
TELEPHONE LINE   
TRIPTYCHS AND TESTS 


18 
 
 
     
 
 
 
 
 
Medication 
Dose 
Range 
DURATION (DAYS) 
PARACETAMOL  500 
mg TAB 
 
500 MG VIA ORAL 
EVERY 8 HRS 
IN CASE OF FEVER > 38th C 
3 DAYS 
AZITROMICINA 500 
mg TAB 
500 MG VIA ORAL 
250 MG VIA ORAL 
EVERY 24 HRS 
EVERY 24 HRS 
FIRST DAY 
SECOND TO FOURTH DAY 
IVERMECTINA  6 MG 
TAB 
 
2 TABLETS < 80 KG VIA 
ORAL 
3 TABLETS between 80-110 
kg VIA ORAL 
4 TABLETS > 110kg VIA 
ORAL 
EVERY 24 HRS 
2 DAYS 
RIVAROXABAN  10MG 
 
1 TABLETA VIA ORAL 
EVERY 24 HRS 
10 DAYS 
Table 4. Earlyintervention treatment policy medications    in COVID-19 patients 


19 
 
 
 
             
            In  relation   toearly interventional treatment policymedications in  COVID-
19patients, Ivermectin, Azithromycin, Rivaroxaban and Paracetamol are considered as part 
of the monitoring of patients with clinical phase leveCovid-19in the Unitsis of first level of 
care of the Northern Delegation.   
 
4.7  Early Intervention Treatment Policy Drugs in COVID-19 Patients 
 
4.7.1  Ivermectin 
 
             Ivermectin is an FDA-approved broad-spectrum antiparasitic. It is usually 
administered with a single dose of 150 μg/kg orally. Ivermectin has been shown to stimulate 
human immunity (including the production of IL-1 and other cytokines, activation of 
superoxide anion production and increased lymphocyte response). 22 
 
             Several studies report antiviral effects of Ivermectin  on RNA viruses such as Zika, 
Dengue, Yellow Iebre F,WestNile, Hendra, Newcastle, Venezuelan Equine Encephalitis, 
Chikungunya, Semliki Forest, Sindbis, Avian Influenza A, Human Immunodeficiency Virus 
Type 1 and Severe Acute Respiratory Syndrome coronavirus 2. 23 
 
Mechanism ofaction, absorption and distribution.  
 
             In vitro studies have shown that Ivermectin has antiviral effect such as that 
performed by Arshad U. et to      where it refers in in vitro studies   a response to SARS-COV-
2  infection where Ivermectina has a maximumsimulated plasma concentration of lung 
(Cmax) / maximum mean effective concentration (CE50) above 1, which means having 
pulmonary concentrations above your CE50 more than 10 times and in lung tissue has a 
value of 20.01(Cmax)/  (CE50) and means  presenting lung concentrations above your CE50 
by more than 10 times. 24  Similarly,  that performed by Caly L, et al. recently showed that a 
single dose treatment with Ivermectin  induced a reduction of approximately 5000 times in 
the viral RNA of SARS-CoV-2 at 48 hrs in a cell culture model Vero-hSLAM.  Mentioning that 
Ivermectin is not if handled at a standard dose, making it a strong candidate for evaluation 
in clinicaltrials. 22. 
 
 
 
 
 


20 
 
 
         In addition, no toxicity of the drug has been seen. Ivermectin is known  to inhibit the 
nuclear amount of viral and host proteins. Virus integrase protein and importin (IMP) α/β I  
 
is  responsible for the nuclear amount which increases infection. Because most viruses are 
dependent on IMP α/β I,  Ivermectin  inhibits the amount andinhibits viral replication. 25 
 
            Within  the pharmacokinetic action of absorption and elimination of Ivermectin as 
possible treatment of COVID-19  stands out what is mentioned  by Momekov G. et al.  with  
pharmacokinetic absorption parameters of 20.2 - 38.2 C max (ng/mL) and elimination 
parameters of 3.1 - 7.57 CI (1 kgx1dayx 1) at a dose of6mg of Ivermectin, considering the 
expectation of reliable data from controlled studies. 26 
 
Therapeutic uses and dosages 
 
            A conventional dose (200≤ g/kg) of  Ivermectin is recommended asa  safe regimen in 
human therapy. 23 
 
Use of Ivermectin in COVID-19 
 
           Randomized Clinical Trials(ECA) that  have used Ivermectin as a treatment for COVID-
19 patients have been conducted, however some studies are still in the recruitment phase.  
27  WHO and PAHO encourage the use of unproven therapies in the context of a randomized 
clinical trial (ECA). 28 
 
          A study conducted by Drosedal S. et. al.  refers to the fact that  clinical efficacy of 
Ivermectin has been established in combination with hydroxychloroquine. 29  The  
randomized clinical trial (Phase 1 pilot study) conducted by Gorial F. et  al. where they 
evaluate the effectiveness of Ivermectin as treatment en patientsCOVID-19 , with criterios 
of inclusion in over 18 years of age, diagnosis with positive polymerase chain reaction test 
(PCR) <3 days and hospital admission to the Al-Shifa'a Hospital Center, initial results are 
reported in 16 patients with treatment based on Ivermectin 0.2mg/kg single dose, 
Hydroxychloroquine 400mg on the first day and then 200mg orally for 5 days, Azithromycin  
500 mg during the first day and then 250mg for 5 days, 4-week follow-up, with initial 
referred results of average age 44.8 years (±10.6), male sex 68% (n-11), mild symptoms 
56.3% (n-9), moderate symptoms 43.8 (n-7), predominantly cough 81.3% (n-13) and fever 
68.8% (n-11), with presencia de comorbilidades (diabetes mellitus e hipertensión arterial  
en  3 pacientes, (NCT04343092, US National Library of Medicine, 2020). 30 
 


21 
 
 
 
 
            There is a   case-series study, prepared by Aguirre-ChangG.  demonstrating  an 
Ivermectin treatment scheme for patients with COVID-19, with 6 mg tablets; with adult 
doses of 2 tablets per day for 2 days, weighing between 80 and 100 kg; give  3 tablets a day 
and > 110 kg; give 4 tablets a day for 2 days, without reports of risks during use in this dose. 
Considering  initiating therapeutics  in COVID-19  patients with mild symptomatology    (mild 
severity), during the   onset days of symptoms 1 to 5 days of COVID-19,   in home isolation  
with  health care.  31 
 
             Given these results from clinical trial studies  using Ivermectin,further evidence isstill 
needed for the treatment of COVID-19 infection,as referred to  in Lespine  A. et al.   
considering the need for more research to better evaluate the effectiveness of Ivermectin 
for the treatment of respiratory viruses such as SARS-CoV-2. 32 
 
4.7.2 Azithromycin 
 
              Azithromycin  is a drug in the macrolide family. Macrolides and cetolides are 
effective in treating respiratory infections caused by common pathogens of community-
acquired pneumonia. Except for  Azithromycin,all have important pharmacological 
interactions by inhibitinghepatic CYPenzymes. 33 
 
Mechanism of action 
 
               This type of antibiotics are bacteriostatic that inhibit protein synthesis by reversible 
binding with the 50S ribosome subunits of sensitive microorganisms, at or very close to the 
site for chloanphenicol binding. 33 
 
              Research shows that Azithromycin  acts as a weak lipophilic acidotrophic base which 
modulates the pH of the endosomas and Golgi apparatus. This leads to in vitro effects 
onintracellularorganelos similar to the conferidos effects by hydroxychloroquine. 25 
 
Antimicrobial activity 
 
             Azithromycin  has appropriate activity against Moraxella catarrhalis, Chlamydia spp, 
L. pneumophila, B. burgdorferi, M. pneumoniae and H. pylori. It has intense activity against 
Mycobacterium avium-intracellulare, itself as against some protozoars, such as Toxoplasma 
gondi,Cryptosporidium  and  Plasmodium  spp. 33 


22 
 
 
 
 
Absorption 
 
         Oral Azithromycin  is rapidly absorbed and distributed throughout the body, except for 
the brain and CSF. It should not be administered with food. It can also be administered 
intravenously, resulting in plasma concentrations of 3 to 4 mcg/ml after an infusion of 500 
mg per 1 hour. 33 
 
Distribution 
 
        Azithromycin  has extensive tissue distribution and high concentrations in cells 
(including phagocytes), resulting in much higher concentrations in tissues or secretions, 
compared to simultaneousserum concentrations. 33 
 
Elimination 
 
         Azithromycin  undergoes some liver metabolism to disable metabolites, but biliary 
excretion isthe mainroute  of elimination. Only 12% of the drug is eliminated without changes 
in urine. The  average elimination time is  40 to 68hours and lasts because the tissueuptake and 
binding are extensive. 33 
 
Therapeutic uses and dosages 
 
         Azithromycin  should be given 1 hour before or 2 hours after meals when administered 
orally. For outpatient treatment of community-acquired pneumonia, pharyngitis or skin 
infections, an impregnation dose of 500 mg is used on the first day and then prescribed 250 
mg  daily for days 2 to 5.   Azithromycin is an appropriate treatment for community-acquired 
pneumonia, in hospitalized patients it is often added to a cephalosporin to coveratypical 
respiratory pates. 33 
 
Side effects 
  
          Macrolide antibiotics cause QT prolongation by an effect on potassium ion ducts. 
Therefore, Azithromycin  may be associated with a small increase in the risk of cardiac death. 
33 
 
 
 


23 
 
 
 
 
Mechanism of action of Azithromycin  in COVID-19 
 
             Azithromycin has in vitro effects on COVID-19 as  Choudhary R. et al refers in its in 
vitro study on intracellular organelles  with COVID-19 infection,  Azithromycin  acts as a 
weak lipophilic acidotrophic base that modulates the pH of endosomas and the network   
Golgi's device. 25  Other authors have referred to other mechanisms of action of COVID-19, 
as referred to by Sargiacomo  C. et. al. questioning that a treatment to prevent Coronavirus 
infection such as Azithromycin that acts functionally as an anti-inflammatory drug and 
reduces senescence-associated secretory phenotype (SASP) mediators, such as IL-1beta and 
IL-6; in addition to Azithromycin  also inhibiting replication of other viruses, such as Zika and 
Ebola. 34  Rahman MT. refers that  Azithromycin  inhibits viral replication and IL-6 
production, IL-1 or IL-1R, suggesting this drug for the prevention and treatment of COVID-
19 disease. 35  Dos Santos WG.et the. refers to the in vitro concentration EC50 (effective 
concentration of 50%) for  Azithromycin  against SARS-CoV-2 was determined as 2.12 M 
after a subsequent incubation period of 72 h of infection. It also refers to the that most 
cytokines induced  by Azithromycin are related to the response to viral infection and, in 
turn, induce resistance to viral replication in target cells. 36  In  vitro  Azithromycin   is 
approved by the FDA (U.S.  Food and Drug Administration) because it  reveals its potential 
inhibition of SARS-CoV-2 replication. 37 
 
Absorption and  distribution of  Azithromycin in COVID-19 
             
            Within the pharmacokinetic action of absorption and distribution of Azithromycin as 
possible treatment of COVID-19  stands out the referred by Arshad U. et to     which 
Azithromycin has a maximum simulated plasma concentration of lung (Cmax) / maximum 
mean effective concentration (CE50) above 1, which means presenting lung concentrations 
above your CE50 more than 10 times and in lung tissue has a value  of 16.04(Cmax)/  (CE50) 
and means  presenting lung concentrations above your CE50 by more than 10 times. 24 
 
 
Use of Azithromycin  in COVID-19 
 
             Randomized clinical trials that have used Azithromycin as a  treatment for COVID-19 
patients have been  conducted as  Gautret P, et al. 36 COVID-19 patients, forming three 
groups, group 1 (control) of 17 patients, group 2 (HQN monotherapy) of 19 patients and 
group 3 (AZT and HQN) of 11patients, with the aim of describing the results of the negative 


24 
 
NASopharyngeal PCR virology test up to 6 days of follow-up, with a result of On day 4, 83% 
of patients treated with hydroxychlorokine   
 
 
and Azithromycin  were virologically cured, compared to 50% patients treated with 
hydroxychlorocin alone, and 25% in the control group and on day 6, 100% of patients 
treated with hydroxychloroquine and  Azithromycin were virologically cured, compared to 
57.1% patients treated only with hydroxychloroquine, and 12.5% in the control group, both 
statistically significant follow-ups p < 0.05 and p< <0.001, respectively.  33 
 
              Showing significant difference in recovery days   using Azithromycin in a Sekhavati  
E. et recluto ECA in 202 patients with COVID-19, where they gave in one case group (n-56) 
Azithromycin  500 mg orally daily, lopinavir / ritonavir 400/100 mg, twice daily and 
hydroxychloroquine 400 mg daily, orally; and the control group (n-57) lopinavir / ritonavir 
400/100 mg, twice daily and hydroxychloroquine 400 mg daily, orally, for 5 days treatment, 
with a statistically significant result of a shorter duration of hospitalization in the group of 
cases vs. control group (4.61 days versus 5.96 days; P x 0.02). 38 
 
               Recommendations are available to indicate Azithromycin as a combination therapy 
in patients with COVID-19 as referred to by Gautret P, et al. where  it concludes according 
tothe resultsobtained s suggests the combined use of hydroxychloroquine with 
Azithromycin for its synergistic effect on the treatment of patients with COVID-19, and for 
the effectiveness of Azithromycin in preventing severe respiratory tract infections when 
administered in patients with viral infection. 33 
 
There are ECAs that are in the realization of field work: 
• Hinks et al.  they are conducting a randomized clinical trial in 800 patients with 
COVID-19, where they aim to evaluate the effectiveness of Azithromycin 500 mg 
once daily for 14 days to reduce and/or prevent complications of lower respiratory 
treatment with follow-up for up to 28 days of follow-up. 39 
 
• Akram J. et al, are designing a multicenter randomized clinical trial in which seven 
comparative groups with drugs will be held where Azithromycin will be included as 
monotherapy and as a triple regimen, performing it in 470 patients, with the 
outcome that will be a laboratory result with COVID-19 PCR test negative to 7 days 
of follow-up. 40 
 
           Azithromycin is a consumer drug for SARS-Cov2 (COVID-19) approved by the U.S. Food 
and Drug Administration. 30 


25 
 
 
4.7.3 Rivaroxab 
 
Use and use in COVID-19 patients   
 
            SARS studies conclude that initialtreatment with HBPM reduces mortality  by 48% at 
7 days and 37% at 28 days and achieves a significant improvement in oxygen blood 
pressure/O2 inspired fraction (PaO2/FiO2) by mitigating microtrombo formation and 
associated pulmonary coagulopathy. In addition, in studies of critical patients, the use of 
HBPM decreased the inflammatory condition22. Therefore, studies derived from COVID-19 
use HBPM in all cases during admission into prophylactic doses (enoxaparin 40-60 mg/day) 
for at least 7 days. 41 
 
            The addition of low doses of Ribaroxaban  (2.5 mg twice daily) to standard 
medication in patients after surviving acute coronary syndrome (ACS) was associated with 
a significantreduction in mortality over an average treatment period of13.3 months. 42 
 
            A beneficial effect of rivaroxaban 2 2.5 mg daily in combination with aspirin (100 mg 
daily; double-route inhibition; DPI) was then confirmed by the COMPASS Trial 
("Cardiovascular results for personas usinganticoagulation strategies") evaluating clinically 
stable patients with coronary heart disease (CAD), as well as patients with stable periphery 
arterial disease (PAD) or carotid arterydisease withcoVID-19 symptoms. 42 
 
           Antiviral therapies interact strongly with DOAC (Oral Anticoagulants- Ribaroxaban), 
because both are substrates of glycoprotein P and /or based on cytochrome P450 metabolic 
pathways. Therefore, concomitant administration of DOAC And Antiviral Medicinal 
Products has the potential to dramatically increase DOAC anticoagulant plasma level, which 
increasesthe risk ofbleeding. 43 
 
           Which obviously speaks of hospitalized patients with a history of consumption, 
making it viable in outpatients and not for hospitalization. The image can assess the 
bioavailability that persists in patients with post-hospitalization antivirals + DOAC and the 
bioavailability of patients with prior use of DOAC prior to hospitalization.  
 
           Although the potential of antiviral agents to increase the plasma concentration of 
DOAC, as well as their risk of bleeding, it is well known that there is no agreement on the 
most appropriate clinical management in these circumstances. An alternative option might 
be to adjust thetwo is (when available). 43 
 
 


26 
 
 
 
 
 
         Comparison of Rivaroxaban  with low molecular weight heparin  Rivaroxaban  10 mg 
once daily has been compared with HBPM or fondaparinux in more than 12,000 patients in 
phase III (CANCER COLORRECTAL), randomized studies in the prevention of VTE (venous 
thromboembolism) after major orthopedic surgery.   44 
              
         In study RECORD 2, 2509 patients scheduled to undergo total elective hip 
replacement were randomized to receive oral Rivaroxaban  10 mg once daily for 31 to 39 
days or enoxaparin 40 mgonce daily via theirbcutaneous for 10-14 days. 44 
 
          Extended prophylaxis with Rivaroxaban  reduced the incidence of deep vein 
thrombosis (symptomatic or asymptomatic detected by bilateral venography), non-fatal 
pulmonary embolism and mortality from all causes up to days 30–42 (absolute risk 
reduction 7.3%, CI 95% 5.2–9.4; p <0.0001) without a significant increase in any 
bleedingduring treatment. 44 
 
           Cancer therapy is predominantly given in the outpatient environment, leaving many 
cancer patients at extended risk. Two large randomized trials in mixed cancer populations 
have evaluated extended prophylaxis with heparin event rates and absolute benefit were 
low, and guidelines recommend routine thromboprophylaxis in such patients. (6) 
Rivaroxaban  is powerful, oral, highly selective. Direct Xa factor inhibitor and is effective for 
primary and secondary thromboprofilaxis.   45 
 
           The intercommunication  between  coagulation and inflammatory pathways has been 
well documented. Dugina T.N.    referred to as protease activated  receptors (PAR) 
comprising 4 subtypes (PAR1 -PAR4) with a mechanism based on a proteolytic binding. The 
endothelium, platelets, pro-inflammatory cytokines and  various  proteases |e.g.  Tissue 
factor(TF),  Xa factor,  thrombin|, through the activation of PAR receptors, are points of 
contact between these two pathways.   46 
 
           Reducing the production of Thrombin by inhibiting Factor  Xareduces 
plateletactivation, decreases the production of inflammatory cytokines, prevents the 
progression of atherosclerosis  and decreases plaque instability. 
 
 
 


27 
 
 
            Ning Tang and  collaborators. refers   in its retrospective cross-sectional study with 
anticoagulant treatment to patients with COVID-19, the D-dimer was greater than 3.0 g/ml 
(6 times the upper limit of normal, six ULN),   finding a reduction of approximately 20% in 
mortality with heparin treatment (32.8% vs 52.4%, P .017).   47 
 
           In a  quasi-experimental study  of Guerrero M.I.  et al. current phase  of termination 
of   discussion and analysis, the null hypothesis is rejected      and refers to the case that if there is a 
change in the frequency of patients recovered from 80 to 90  % in patients diagnosed with 
COVID-19 after treatment of imperfection  Acetaminophen,  Ivermectin,  Azithromycin,  
Rivaroxaban in patients with COVID-19 from U.M.F 13 during the July-August 2020 period. 48 
 
 
 
 


28 
 
 
4. Justification 
 
           Emerging coronaviruses (CoVs) such as SARS-CoV-2 cause serious diseases in humans 
and to date there is no approved treatment available for use. In recent months since the 
SARS-CoV-2 pandemic declaratory worldwide, there have been many initiatives to assess 
the ability of various drugs against SARS-CoV-2, in addition to current research to develop 
an effective vaccine. The role of Ivermectin  against SARS-CoV has been demonstrated in 
vitro and it is suggested that it could have an effect against SARS-CoV-2. In an  observational 
study mortality was lower in the  Ivermectin group  (7.3% versus 21.3%) and overall 
mortality rates were lower with  Ivermectin  (1.4% versus 8.5%; HR 0.20 CI 95% 0.11-0.37 p 
< 0.0001), phase 3 clinical trials are needed to verify these findings, for the benefit of the 
population 
under 
COV-2 
SARS 
disease 
(COVID-19). 
Of 
the 
anticoagulants     
Rivaroxaban,according to the effects of inhibition of factor  Xa and the formation of 
Thrombin, goes beyondanticoagulation through interaction with PAR receptors, due to 
having anti-inflammatory effects, decreasing arteriosclerosis and platelet aggregation. A 
reduction of  approximately 20% in mortality with anticoagulant treatment has been 
reported. The management of  first-level patients for the evaluation of COVID-19 patients 
the clinical and paraclic evaluation of a suspected or confirmedcase ofCOVID-19,  should 
adhere to current medical practicesaccepted for patients with acute  respiratory infections 
and 
comorities. 
 
So 
it 
is 
essential 
to 
determine 
vital 
signs 
and 
pulse 
oximetry,theconsultation should be based onsplit decisions. It has been  documented that 
themodel of care, focused on the environment, is more beneficial in terms of 
understanding, satisfaction, adherenceto treatment and reduction of complications.   The 
technical information thatmatters to you about diagnosis, treatment and follow-up  (follow-
up and reference consultation) should be transferred to the patient in a clear and simple 
way, so that the taking decisions is jointly andwell-supported. So within the guidelines for 
patient care   by COVID-19 refers that it is suggested to make a follow-up consultation at 
24-48 hours, in application to the "Standardized GuidelineforSurveillance and Requestology  
and by COVID-19 Laboratory", especially in patients of high riesgo. So an    outpatient 
monitoring model for patients with COVID.19 carried out by the  Deconcentrated 
Administrative Operation Body of the Northern Federal District of the Mexican Institute of 
Social Security (I.M.S.S.)  considering    the use of Information and Communication 
Technologies, to minimize risk of contagion in top-level  health care personnel is necessary 
to cover in the patient terms of understanding, satisfaction, adherenceto treatment and 
reduction of complications. So evaluate in patients by COVID-19, in mild phase or newly 
diagnosed, especially in those at high risk for having comorities, the benefits of a patient-
centered care model, in which important technical information on diagnosis, treatment and 
follow-up is transferred to you in a clear and simple way.  


29 
 
 
 
               This care model involves outpatient monitoring, which considers the use of 
Information and Communication Technologies (video call monitoring), to minimize the risk 
of contagion in first-level health care personnel and to improve the patient's understanding, 
satisfaction, adherence to treatment and reduce complications. 
 
 
5. APPROACH TO THE PROBLEM 
 
        Lto coronavirus disease (COVID-19) is caused by SARS-COV2 and represents 
thecausalagent of a life-threatening disease potential that isa major global public 
healthproblem. Person-to-person transmission of COVID-19 infection led to the isolation of 
patients who subsequently received a variety of treatments. Extensive measures to reduce 
human-to-humantransferof  COVID-19 have been implemented to control the current 
outbreak. 50 
 
          This has forced rapid action not only to try to contain the advancement of contagions, 
but also to develop protocols of action that reduce mortality. 51  Drugs  such  as Ivermectin 
inrelation to the safety of this drug are approved for human use by the FDA for various 
parasitic and skin infections, it has been proposed in pharmacokinetic simulations that for 
possible management of patients   with COVID-19 las doses should be high, thereare 
severalstudies in which high doses of Ivermectin have been shown to have commptable 
safetyat standarddoses. 52.53 However, there is a study in Lima,  Peru,which reports the 
therapeutic safety of Ivermectin in humans with COVID-19 and describes a significant 
decrease in the fatality rate of 6.1 times lower compared to patients who did not use 
Ivermectin (1.4 vs.  8.5% ,  p< 0.0001).  31  Clinical  trials are in the recruitment phase where  
Ivermectin is used for the treatment of COVID-19 infection. 32  WHO and PAHO encourage 
the use of unproven therapies in the context of a randomized clinical trial (CCA). 28  
Anticoagulants have reported up to 20% in reducing mortality (heparin),    Ribaroxaban is 
effective with inhibition of PAR1/PAR2/PAR4 receptors through X Factor blockage and 
Thrombin formation, have anti-inflammatory effects, decrease arteriosclerosis and platelet 
aggregation. 46.47 
 
          Karen Donelan's reports in a cross-sectional study, which referred to 254 people 
visited by Telemedicine for 15 minutes,   referred with answers > 90%  with "if, definitely  
agree" rating,  in explaining things in an easy-to-understand way, whether patient care was 
heard and whether she felt that the doctor had spent enoughtime on the patient when 
making the video call. 49  A Specific  Telemedicine Working  Method is being carried out  


30 
 
 
 
during Phase 3 of COVID-19 contingency in IMSS rightholders to followup patients with 
clinicaldiagnosis, confirm orand graduates of COVID-19 fromoperation  Administrativa  
Dfocused on Northederal  F-D,within the specificobjectives is to detectearly signs and 
symptoms of possiblecomplications as well as to offer a policy of early intervention 
treatment in top-level rightholders.  20 
 
           Considering also what was reported by Guerrero M.I. et al., 48 in a quasi-experimental 
study in the current phase of completion of discussion and analysis where there is a change 
in the frequency of patients recovered from COVID-19 of 80-90% after an early intervention 
treatment (paracetamol, Ivermectin, Azithromycin , Rivaroxaban) of UMF 13 during the 
period of July-August 2020. It is necessary to carry out a double-blind randomized clinical 
trial where a treatment (Azithromycin / Ivermectin / Ribaroxaban / Paracetamol) of early 
intervention (during the first 5 days of COVID disease -19) in patients entitled to the first 
level of care performing monitoring with video calls, the following research question is 
formulated: 
 
Research question  
 
What is the percentage of patients who change their clinical evolution in patients with 
COVID-19 under treatment with Azithromycin / Ivermectin / Ribaroxaban /Paracetamol vs. 
Azithromycin / Ribaroxaban / Paracetamol followed by video call for 14 days from U.M.F 13 
and U.M.F 20 from I.M.S.S., in the period December 2020- February 2021. ? 
     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


31 
 
 
 
6. Objective 
 
General Objective.   
• Evaluate the percentage of patients diagnosed with COVID-19 who modify their 
clinical evolution under an early intervention comparative treatment in U.M.F 13 
and U.M.F 20 U.M.S.S. speakers during the period December  2020- February 2021.  
 
Specific objectives.  
• Describe sociodemographic characteristics (sex, age, schooling, occupation, marital 
status) in patients with COVID-19 under treatment with Azithromycin / Ivermectin / 
Ribaroxaban /Paracetamol vs. Azithromycin / Ribaroxaban / Paracetamol followed 
by video call for 14 days from U.M.F 13 and U.M.F 20 from I.M.S.S., in the period 
December  2020- February 2021. 
• Record  laboratory  results performed  in patients with COVID-19 under treatment 
with Azithromycin / Ivermectin / Ribaroxaban /Paracetamol vs. Azithromycin / 
Ribaroxaban / Paracetamol followed by video call for 14 days from U.M.F 13 and 
U.M.F 20 from I.M.S.S., in the period December  2020- February 2021. . 
• Evaluate adverse drug reactions for follow-up days  in patients with COVID-19  under 
treatment with Azithromycin / Ivermectin / Ribaroxaban /Paracetamol vs. 
Azithromycin / Ribaroxaban / Paracetamol followed by video call for 14 days from 
U.M.F 13 and U.M.F 20 from I.M.S.S., in the period December  2020- February 2021. 
• Estimate clinical symptoms per follow-up days in patients with COVID-19  under 
treatment with Azithromycin / Ivermectin / Ribaroxaban /Paracetamol vs. 
Azithromycin / Ribaroxaban / Paracetamol followed by video call for 14 days from 
U.M.F 13 and U.M.F 20 from I.M.S.S., in the period December  2020- February 2021. 
 
 


32 
 
7. WORKING HYPOTHESES   
 
 
 
• Null Hypothesis: There will be no change in clinical evolution ≥ 25 % of patients 
diagnosed 
with 
COVID-19 
under 
early 
intervention 
treatment 
with 
Azithromycin/Ivermectin/Ribaroxaban/ 
Paracetamol 
vs. 
Paracetamol. 
Azithromycin/Ribaroxaban/ Paracetamol for 14 days followed by video call from 
U.M.F 13 and U.M.F 20 from I.M.S.S., during the period December  2020- February 
2021. 
 
• Alternative hypothesis: If there will be a change in clinical evolution ≥ 25 % of 
patients diagnosed with COVID-19 under early intervention treatment with 
Azithromycin/Ivermectin/Ribaroxaban/ 
Paracetamol 
vs. 
Paracetamol. 
Azithromycin/Ribaroxaban/ Paracetamol for 14 days followed by video call from 
U.M.F 13 and U.M.F 20 from I.M.S.S., during the period December  2020- February 
2021. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


33 
 
8. MATERIAL AND METHODS 
a) Study place: 
 
            The study will be carried out in Family Medicine Unit No. 20 and in the U.M.F 
13/H.G.O., Units belonging to the North Deconcentrated Administrative Operating 
Body D.F. of the Mexican Institute of Social Security. 
b) Study groups: Two groups of patients with COVID-19, a group called A that will 
receive treatment with Azithromycin,paracetamol,  Ivermectin  and Rivaroxaban and the 
group called B to be treated  with acetaminophen,  Azithromycin  and Rivaroxaban, will 
beintegrated. 
c) Study Design:  Randomized experimental study,  simple  blind,  prospective, 
longitudinal  and open. 
d) Inclusion Criteria:  
• Right-speaking Patients of Family Medicine Unit No.20 and Family Medicine Unit 
No.13 belonging to the Northern DF of the IMSS. 
• Male and female patients 
• Patients over 18 years of age. 
• Patients with COVID-19 operational definition compliance and confirming P.C.R. 
test.   positive within the first few days of the disease (which are evaluated at the 
first level of medical care). 
• Patients with comorities such as Type 2 Diabetes Mellitus, Systemic High Blood 
Pressure, Overweight or Obesity. 
• Accepting to sign informed consent 
- 
 Related to the Video Call: 
• ImSS Family Medicine Unit No.20 and Family Medicine Unit No.13 belonging to imSS 
North DF have Electronic Equipment Installation for Internet use.  
e) Exclusion Criteria: 
• Patients with severe COVID-19 (Ameriten sent immediate to second level of care, 
hospital)  
• Patients with any Pathological Personal History of Haematological Diseases. 
• Patients allergic to macrolides  (Azithromycin) and Ivermectin.   
 
 
 
 
 
 


34 
 
 
Sample size and sampling. 
 
          It is performed for sample size calculation, the Difference of Proportions formula 
presented inDr.  Talavera JO et.   49  and according to laboratory modification values in 
PATIENTS with COVID-19 of the randomized clinical trial study of Gautret P. Et al. 33  where group 
A of patients was treated with azithromycin/hydroxychloroquine and the second group B 
was treated with hydroxychloroquine. By evaluating laboratory modification in COVID-19 
patients after 4 days the proportion of patients who managed to modify it obtained a 
modification difference of 25%. 
 
 
 
           Assuming that for the study problem, group A of patients receiving treatment with 
Ivermectin /Azitromycin/ Ribaroxabán /Paracetamol is expected to succeedin 50% of cases, while 
group B will be treated with Azithromycin / Ribaroxaban / Paracetamol to succeed in 25% 
of cases, the values in the formula will be replaced as follows: 
 
Where: 
Za= (a= 0.01) 2.576 
Zb = (b= 0.10) – 1.645   
P1= 0.50 
P2= 0.25    
 P1 - P2 = 0.25 
 
No. 25.97  - 26 
 
Plus 20% losses n. 31.2 x 31  patients are needed in the study.    Group formation: 
 
 
 
 


35 
 
 
           The above result has to be rounded to the upper digit. In this way, the sample should 
include 31 subjects in each study group if one wants to have a 90% chance (90% power) to 
detect at least a 25% difference in the success rate of clinical evolution modification 
between the two treatment groups that are exemplified. 
 
             Random numbers generated by draw will be used for the formation of the groups in 
which the patient arriving will take a piece of paper which will have the number of the group 
to which it will be assigned. With a type of block randomization, A (Azithromycin, 
acetaminophen,  Ivermectin  and Ribaroxaban) andB (acetaminophen,  Azithromycin,  and 
Ribaroxaban), each 31 participants. 
 
         The mechanism used to implement the random mapping sequence was the use of two 
containers that will include 31 blue boxes and another 31 orange with color identification 
to the assigned treatment, to be performed by an intern doctor.    
 
         The staff who generated the random assignment sequence will be an intern physician 
(it will be their only role in the study protocol) and who selected the participants and 
assigned the participants to the interventions will be an associate researcher (it will be their 
only role in the study protocol).  
 
        He remained blinded after assigning the interventions to the given patient unknown to 
what treatment he is receiving and to the assigned treatment group A or B. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


36 
 
 
VARIABLES 
1.- DEMOGRAPHIC VARIABLES 
Age 
Conceptual definition: Period of time elded from birth in years  
Operational definition: It shall be measured through a Questionnaire carried out at the 
beginning of the study with unarmed consent foreach of the two groups considered 
agereached in years at the start of the study. (See Annex 2) 
Variable type: Qualitative categorical 
Measurement scale: years  1 ) 40-50 years 2) 51-60 years 3)  61 – 70 years   
Sex 
Conceptual definition: Phenotypic and genotypic characteristics that identify the  
Individual as male and female 
Operational definition: It will be measured through a Questionnaire carried out at the 
beginning of the study withunarmed consent for each of the two groups   considering  sex 
atthe beginning of thestudyor.   (See  Annex 2) 
Variable type: Nominal dichotomous qualitative 
Measuring scale: 1) Male  2)  Female 
Marital status 
Conceptual definition: A particular condition that characterizes a person in what makes 
their personal bonds with individuals of another sex or of the same sex.  
Operational definition: It shall be measured through a Questionnaire carried out at the 
beginning of the study withunharmed consent for each of the two groups considering    the 
civil situation at the time of the study.  (See  Annex 2) 
Variable type: Nominal dichotomous qualitative 
Measuring scale: 1)  Single. 2)  Married. 3)  Widow. 4)  Separated. 5)Free Union 6)  Divorced
 
 
 


37 
 
 
 
Occupation  
Conceptual definition: The type of work you  do that generates economic resources 
Operational definition: It shall be measured through a Questionnaire carried out at the 
beginning of the study with unarmed consent foreach of the two groups considering the 
occupationat the time of the study. (See  Annex 2) 
Variable type: Nominal dichotomous qualitative 
Measuring scale: 1)  Part-time work. 2)  Full-time work. 3)  Housewife 4)  Pensioned 5)  
unemployed 6)Ortro 
Schooling  
Conceptual definition: years studied and approved in some type of educational 
establishment. 
Operational definition: It will be measured through a Questionnaire conducted at the 
beginning of the study withunarmed consent for each of the two groupsconsidering 
schooling at the beginning of the study. (See  Annex 2) 
Variable type: Nominal dichotomous qualitative 
Measuring scale: 1)  Sinstudies 2)Pre-school 3)Primaria 4)Secundaria 5)Prestorative or 
baccalaureate 6)Carrera técnica 7)Licenciatura 8)Otros 
 
2.- INDEPENDENT VARIABLE 
Patients with 2V-2 SARS (COVID-19) 
Conceptual Definition: A viral disorder characterized  by Headache, Cough, Fever, 
Conjunctivitis, Myalgias, Arthralgias, Rhinorrhea, Odinophagia, Anosmia, Chest Pain, 
Dyspnoea and   other symptoms of VIRAL NEUMONIA, caused by an  agent  known as 
Coronavirus SARS-CoV-2 dthe genusBETACORONAVIRUS  . 
Operational Definition: Confirming PCR tests will  be performed on all patients with 
suspected  VF-2 SARS (COVID-19).    
 
 


38 
 
Variable Type: Qualitative 
Measuring scale: Nominal 
Measuring Unit:  SARS 2 Patient (COVID-19).1,  Suspected  Patient SARS 2 2 (COVID-19)  .. 
3.- DEPENDENT VARIABLE 
Changing clinical developments 
Conceptual Definition: Registration of clinical health conditions as symptoms (Headache, 
Cough, Fever, Conjunctivitis, Myalgias, Arthralgias, Rhinorrhea, Odinophagia, Anosmia, 
Chest Pain, Dyspnoea), Adverse Reactions (Diarrhoea, Nausea, Vomiting, Disorientation, 
Dizziness, Asthenia, Equimosis/Petechiae, Vertigo, Tinnitus, Urticaria, Hemorrhage, 
Angioedema, Palpitations, Chest pain) and laboratories(hematic biometrics, C-reactive 
protein, Dimero-D, ferritin, prothrombin time, thromboplastin time, lactic dehydrogenase) 
of patients with Covid-19 Mild Clinical Phase performed through monitoring (See Table 1 ) 
for 14 days of approx. lasting 15-20 minutes, following administration in two group (A and 
B) of Azithromycin/Ivermectin/Ribaroxaban/ Paracetamol vs. Azithromycin/ Ribaroxaban/ 
Paracetamol (See Table 4). 
Operational Definition: The patient with the presence of COVID-19 confirmed by PCR test 
to participate in the study, the granting of the medicinal product randomly to belong to 
group A or B, is initiated after the signing of informed consent (Annex1), 
Azithromycin/Ivermectin/Ribaroxaban/ Paracetamol vs. Azithromycin/ Ribaroxaban/ 
Paracetamol (See Table 4),to be followed for 14 days by video call (15 to 20 min approx. 
daily) to the patient and the presence or absence of clinical symptoms, adverse reactions 
and laboratory registration is recorded daily. 
Variable Type: Qualitative, Quantitative (Laboratories) 
Measurement scale: Nominal, Interval (laboratories) 
Measurement Unit: Symptoms of fever, cough, headache, myalgias, odinophagia, anosmia, 
rhinorrhea, arthralgias, chest pain, dyspnoea, conjunctivitis)-1 (SI), 0 (NO). 
Adverse reactions 1 (SI), .0 (NO). 
Laboratories - continued reason 
 
 
                                                                                                                                                                                                   
Overview of the Study (see Figure 1 and 2).  
 
1.- Project management  


39 
 
(a) Communication with clinical department heads and directors for the authorization of 
instrumentation. 
      You will go to U.M.F. No.20 with the director of U.M.F No. 20 and the director of the 
U.M.F.  No. 13 for the authorization of the implementation of the research project.      
b) Recruitment of pollster staff                                                                                                                                       
    Six U.M.F. passing doctors will be assigned.  20 and 7 U.M.F. passing doctors.  13 to 
serve as a pollster.      
c) Training of project surveyor staff.                                                                    
    The surveyor staff will be trained by the project manager in Classroom 1 of the U.M.F. 
20 with a duration of 2 hours where it will be reported on: 
-Identify the intern  physician to patients who are diagnosed with COVID-19 confirmatory 
testing with care in family medicine unit No. 13 and No. 20 of the IMSS, based on the case 
notification by the Epidemiology service, meeting the criteria of inclusion of the study, you 
are called by telephone so that upon informed consent and your signature if you agree to be part of the 
study, a triptych of home care is granted for patients with COVID-19 and early intervention 
treatment medicine. 
   -Guidelines for the patient who is identified by the family doctor who is based on the 
COVID-19 response teams, meeting the criteria of inclusion to be granted informed consent 
and signature if he agrees to be part of the study, as well as a triptych of home care for 
patients with COVID-19 and early intervention treatment medication. (See Annex 1)  
  - The characteristics of the video call made via Wi-Fi every 24 hrs for 14 days lasting 
approximately 15 to 20 minutes and question the patient about the major and minor 
symptoms of COVID-19 disease, adverse reactions, dyspnoea and symptom information and 
warning signs for reference to the second level of care will be disclosed to the intern. (See 
Annex 2)      
 
 
 
 
 


40 
 
 
2.-Fieldwork 
           The study will be conducted in the family medicine unit (U.M.F. No. 13 and No. 20 of 
the IMSS, according to the sample size for convenience entering the U.M.F 20 during the 
period of November-December 2020, captured by the COVID-19 respiratory module 
service, making video calls by intern doctors, contemplating 15 minutes of video call per 
patient , lasting approximately 3 total hours per day of care for each intern. Video call times 
will be open within 8:00 a.m. to 8:00 p.m.   
2.1. Interview plan 
          For the first interview of each patient will be given a space of 15 minutes that will be 
aimed at explaining in a general way what is the monitoring of the clinical status with video 
calls, and interrogate about personal data (identification sheet and personal history), all 
with prior presentation by the interviewer (indicating full name, position and category, unit 
of which the call is made and name of the protocol). 
            Subsequently, it shall follow the entire symptomatology section, which will ask what 
is set out in Annex 1, first symptomatology of the operational definition for COVID-19 (to 
assess whether there is improvement or clinical deterioration), and adverse effects of 
medicinal products (if it has any of those mentioned in Annex 1).  
            At the end of questioning about the symptomatology the interview will be 
terminated, explaining in advance to the patient that the number of which the call was 
made should not be used for any reason other than for the scheduled video calls, and that 
if he/she were to present any symptoms of severity he should go to the emergency 
department closest to his home , this is because video calls are for research purposes only. 
         Interviews are with a scheduled follow-up of 14 days from day 1, reminding the patient 
on the 14th that it will be the last day of follow-up of symptomatology, and that if it were 
to present any symptoms of severity from this day, the indication will be the same as that 
mentioned from day 1 (go to the emergency department assessment). 
           At the end of the interview follow-up each interviewer will append the information 
to a database so that they can then perform analysis of the information. 
 
 
 


41 
 
 
2.2 Delivery of medicine.   
         The patient is informed via video call that meets the criteria of inclusion and prior 
signature of informed consent to go to UMF No.13 for the randomized delivery of the 
medicinal product that will be wrapped in blue paper with the written legend of drug 
consumption according to Table  4 (described in this protocol), this procedure is performed 
by 
the 
 
intern 
 
doctor, 
which 
is 
known 
as 
group 
A 
(experimental)  
Azithromycin,acetaminophen,  Ivermectin and Rivaroxaban and group B (control) 
acetaminophen, Azithromycin,  and Rivaroxaban.   
Group formation: 
          For the formation of the groups the simple blind randomized sampling method will be 
used in its draw mode in which the patient arriving will take a piece of paper which will have 
the number of the group to which it will be assigned, group A  Azithromycin,acetaminophen,  
Ivermectin  and Rivaroxaban and group B acetaminophen,  Azithromycin,and  Rivaroxaban.   
2.3  Taking laboratories  
         Wi-Fi video call will be given the indication of conducting laboratories (hematic 
biometrics, C-reactive protein, Dimero-D, ferritin,  prothrombintime, thromboplastin time, 
lactic dehydrogenase) taken at the start of treatment and on day 21 of the disease by 
laboratory personnel in HGZ 48 of the IMSS. 
3.- Final evaluation 
Video call tracking is terminated by meeting 14 days of follow-up of patients in the study or 
until you have at least 7 days with reduced symptoms and signs of COVID-19. 


42 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication 
Dose 
Range 
DURATION (DAYS) 
PARACETAMOL  500 mg 
TAB 
500 MG VIA ORAL 
EVERY 8 HRS 
IN CASE OF FEVER > 38th C 
3 DAYS 
AZITROMICINA 500 mg 
TAB 
500 MG VIA ORAL 
250 MG VIA ORAL 
EVERY 24 HRS 
EVERY 24 HRS 
FIRST DAY 
SECOND TO FOURTH DAY 
IVERMECTINA  6 MG 
TAB 
2 TABLETS < 80 KG VIA ORAL 
3 TABLETS between 80-110 kg VIA ORAL 
4 TABLETS > 110kg VIA ORAL 
EVERY 24 HRS 
2 DAYS 
RIVAROXABAN  10MG 
1 TABLETA VIA ORAL 
EVERY 24 HRS 
10 DAYS 
Triptic delivery of 
"DOUBTS YOU MAY 
HAVE DURING THE 
INTERVIEW TRANSCURS 
” 
Patients valued by 
Respiratory Module 
with COVID-19 
suspected or 
confirmed 
Application test 
symptoms and 
signs, adverse 
reactions 
Outcome 
Percentage of patients with 
clinical evolution 
modification(Clinical  symptoms) 
Information about 
symptoms and warning 
signs for second-level 
care reference.  
Informed Consent 
Time 0  
Video call every 24 hrs by medical staff for 14 days  
Tracking  
Delivery of medicines to 
patients Confirmed COVID-
19 , paracetamol, 
Ivermectin,  Rivaroxaban,  
Azithromycin. 
Fig. 1 Study Design Description Part 1 


43 
 
 
 
 
Patients with 
COVID-19 
Group A, treatment with Ivermectin 
/Azithromycin/Ribaroxaban/Paracetamol 
% patients with 
change in clinical 
evolution(Clinical  
symptoms) 
Fig. 2 Study  Design Description Part 2 
No 31
No.  62 
No 31
Randomization 
• 
Percentage of patients with clinical 
evolution modification 
(Clinicalsymptoms)  group A and B. 
• 
Percentage of patients with adverse 
reactions group A and B. 
• 
Registration oflaboratory rultados 
group A and B. 
14 days of  video call tracking 
% patients with 
change in clinical 
evolution(Clinical  
symptoms) 
Group B, treatment with Azitromycin/  
Rivaroxaban/Paracetamol 
It ≥ 25% 


44 
 
 
 
 
 
STATISTICAL ANALYSIS 
 
              Assuming an 25% effectiveness in modifying clinical evolution(symptoms of fever, 
cough, headache, myalgias, odinophagia, anosmia, rhinorrhea, arthralgias, chest pain, 
dyspnoea, conjunctivitis) of  patients diagnosed with COVID-19 under early intervention 
comparative treatment for 14 days followed by video call, with a potency of 90%, an error 
rate type I of 1% and a follow-up loss of 20%; we calculated a total of 62 patients with 
COVID-19, i.e. 31 cases in group A with treatment of Azithromycin/Ivermectin/Ribaroxaban/ 
Paracetamol and 31 in group B with Azithromycin/Ribaroxaban/ Paracetamol treatment 
would be necessary for analysis. Statistical differences were assessed by Pearson's hi-square  
Ctest or Fisher's exact Prueba as categorical variables, as appropriate. The scans will be 
performed in SPSS version 21. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


45 
 
9. ETHICAL ASPECTS 
RISK OF RESEARCH. 
 
         As mentioned in the regulations of the General Health Law, article 17, on health 
research, this research will be category 1, since this investigation does not present any risk 
to the patient, since informed consent prior to the indication of the medicinal product is 
signed and that the patient agrees to take the drug. 
 
CONTRIBUTION AND BENEFITS OF STUDY FOR SOCIETY.  
 
          On the other hand, this research will help to identify in an appropriate and timely 
manner the coVID associated factors as doctors perform interventions to delay or decrease 
the development of this pathology.  
 
Confidentiality. 
 
           The information collected in the clinical records will not obtain the patient's name in 
order to keep the patient confidential.  
 
FORM OF PATIENT SELECTION. 
 
            The review of previously diagnosed patient records with the criteria for inclusion of 
this investigation shall be carried out.  
 
           This research was conducted in accordance with the guidelines and rules governing 
research in Mexico and the world:  
 
HELSINKI DECLARATION 1964  
 
            This statement is based on the review of research by an ethics committee, in turn 
giving rise to new ethics committees for research at the international level. This research is 
classified in category I, where no intervention is performed, so it does not meet the criteria 
to be submitted to an ethics committee.  
 
MEXICAN OFFICIAL STANDARD 012 SSA 3-2007.  
 
              This standard sets out the criteria for the implementation of human health research, 
specifies how research review and approval should be carried out in health institutions, in 
order to protect the rights and well-being of participants.  


46 
 
 
 
 
This research took this standard into account, applying only in some respects, as it will be a 
retrospective investigation, analyzing clinical records.  
 
              Finally, the general guidelines for conducting research at the Mexican Institute of 
Social Security were considered, highlighting the following: "that any research carried out 
in the institute must show a deep respect for the person the life and security of all the rights 
that who participate in them by following the institutional rules in this matter", in particular 
by the Organization Manual of the Head of Teaching and Research Services (Agreement No. 
15; 6 - 84 of 20 June 1984 of the Honourable Technical Council).. 38 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


47 
 
 
10. Physical and  Financial Resources  
 
To carry out this study protocol, UMF 20 facilities of the Mexican Social Security Institute 
were used, with the following resources: 
• HUMANS:   Five researchers; Eleven  intern physicianswill participate in the study protocol 
during the data collection period through the filling of the data collection instrument and the 
realization of the database of patients receiving COVID-19. 
 
• TECHNOLOGICAL: Two Hp 1502 computer equipment with Word and Power Point 
2015 program used for information collection and writing of the study protocol, as 
well as for the analysis of results; OKI printer used for the printing of questionnaires 
and informed consents; access to the external consultation network and comprehensive family 
medicine system used to obtain information from the electronic clinical record of participating 
patients or, where appropriate, the realization of data collection sheet. 
 
• PHYSICAL: Teaching classroom, confidentiality letter, informed consent format, two 
support tables, four pens, printing paper and  fifteen  cell phones. You will also have 
the Triage area for the delivery of the drug which has the drug kit a doctor and a 
nurse.  
 
           The aforementioned resources are provided by the IMSS without increasing the 
demands and inputs available in the medical unit.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


48 
 
11. Timeline of protocol activities 
" PRONOSTIC MODIFICATION IN PATIENTS WITH COVID-19 UNDER EARLY INTERVENTION TREATMENT IN U.M.F 13 AND U.M.F 20". 
 
March 
2020 
April 
2020 
May 
2020 
June 
2020 
July 
2020 
August 
2020 
September 
2020 
October 
2020 
November 
2020 
December 
2020 
January  
2021 
February 
2021 
Delimitation of the subject to be 
studied 
R    
R    
R    
 
 
 
 
 
 
 
 
 
Establish the title of the investigative 
protocol 
R    
R    
R    
 
 
 
 
 
 
 
 
 
Recovery, review and selection of the 
bibliography. 
R    
R    
R    
R    
R    
R    
R    
    
 
 
 
 
Ask research question 
R 
R 
R 
R 
R 
 
 
 
 
 
 
 
Elaboration of the Theoretical 
Framework. 
R    
R    
R    
R    
R    
R    
R    
 
 
 
 
 


49 
 
Conducting justification approach to 
the problem and objective of study 
and working hypotheses 
R    
R    
R    
R    
R    
R    
R    
   
 
 
 
 
Preparation of Materials and 
Methods, Ethical Aspects. 
R    
R    
R    
R    
R    
R    
R    
    
 
 
 
 
Sent the protocol to (CNIC) SIRELCIS 
to request registration 
 
 
 
 
 
 
 
P 
P 
 
 
 
Collecting information 
 
 
 
 
 
 
 
 
 
P 
P 
 
Analysis and discussion of results 
 
 
 
 
 
 
 
 
 
 
P 
 
Final report writing 
 
 
 
 
 
 
 
 
 
 
 
P 
 
 
 
 


50 
 
 
 
12. BIBLIOGRAPHIC REFERENCES 
 
1. World Health Organization. (2020). Coronavirus Disease (COVID-19) Outbreak. 
Retrieved May 06, 2020, from https://www.who.int/emergencies/diseases/novel-
coronavirus-2019 
 
2. Directorate-General for Epidemiology , (April 06, 2020). Epidemiological Warning 
COVID-19 
disease 
by 
SARS-CoV-2. 
Retrieved 
May 
06, 
2020, 
from 
https://www.gob.mx/salud/acciones-y-programas/avisos-epidemiologicos-2020 
 
 
3. Pan American Health Organization , (April 20, 2020). Epidemiological Update: 
Coronavirus 
Disease 
- 
(COVID-19). 
Retrieved 
May 
06, 
2020, 
from 
https://www.paho.org/es/documentos/actualizacion-epidemiologica-enfermedad-
por-coronavirus-covid-19-20-abril-2020 
 
4. World Health Organization 2020. WHO coronavirus disease (COVID-19) dashboard. 
[Internet]. Geneva: World Health Organization; 2020 [Consulted 22 Oct. 2020]. 
Available at: https://covid19.who.int/ 
 
5. World Health Organization (February 24, 2020). Report of the WHO-China Joint 
Mission. 
Obtained 
from 
 
https://www.who.int/docs/default-
source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf 
 
 
6. Epidemiological and Health Intelligence Unit, (May 06, 2020). Coronavirus (COVID-
19)-Daily 
Technical 
Communication. 
Retrieved 
May 
06, 
2020, 
from 
https://www.gob.mx/salud/documentos/coronavirus-covid-19-comunicado-
tecnico-diario-238449 
 
7. Conacyt. (May 06, 2020). Covid-19 Mexico. Retrieved May 06, 2020, from 
https://coronavirus.gob.mx/datos/#DOView 
 
 
 


51 
 
 
 
 
 
 
 
8. Mexican Institute of Social Security. COVID-19. Cumulative cases of COVID-19 in 
Mexico. [Internet]. Mexico: Intersecretariat Commission for the Development of 
electronic government, National Single Window; 2020 [Retrieved 22 Oct.  2020]. 
Available in:  http://educacionensalud.imss.gob.mx/es/coronavirus 
 
9. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, 
Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, 
Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng 
ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group 
for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J 
Med. 2020 Apr 30; 382(18):1708-1720. Doi: 10.1056/NEJMoa2002032. 
 
10. Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, 
N.; et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: 
Implications for virus origins and receptor binding. Lancet (Lond. Engl.) 2020, 395, 
565–574 
 
11. Henry, B. M., Vikse, J., Benoit, S., Favaloro, E. J., & Lippi, G. (2020). 
Hyperinflammation and derangement of renin-angiotensin-aldosterone system in 
COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and 
microvascular immunothrombosis. Clinica chimica acta; international journal of 
clinical 
chemistry, 507, 
167–173. 
Advance 
online 
publication. 
https://doi.org/10.1016/j.cca.2020.04.027 
 
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epidemiological and laboratory surveillance of viral respiratory disease- April 2020. 
https://www.gob.mx/cms/uploads/attachment/file/546206/Lineamiento_estandar
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52 
 
 
 
 
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20. Donelan K, Barreto EA, Sossong S, Michael C, Estrada JJ, Cohen AB, Wozniak J, 
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25. Choudhary R, Sharma AK. Potential use of hydroxychloroquine, ivermectin and 
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26. Momekov G. Momekova D. Ivermectin as a potential COVID-19 treatment from the 
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28. Washington; Pan American Health Organization; Jun. 23, 2020. 3 p 
 
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33. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a 
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Elem Res. 2020 May 26:1–9. Doi: 10.1007/s12011-020-02194-9. 
 
36. Dos Santos WG. Natural history of COVID-19 and current knowledge on treatment 
therapeutic options. Biomed Pharmacother. 2020 Sep; 129:110493. Doi: 
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37. Touret F, Gilles M, Barral K, Nougairède A, van Helden J, Decroly E, de Lamballerie 
X, Coutard B. In vitro screening of a FDA approved chemical library reveals potential 
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10.1038/s41598-020-70143-6. 
 
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M, Pirhayati M, Zendehdel A, Manafi N, Hajiabdolbaghi M, Ahmadinejad Z, Kouchak 
HE, Jafari S, Khalili H, Salehi M, Seifi A, Golestan FS, Ghiasvand F. Safety and 
effectiveness of azithromycin in patients with COVID-19: An open-label randomised 
trial. 
Int 
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Antimicrob 
Agents. 
2020 
Oct; 
56(4):106143. 
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D, Lasserson D, Pavord ID, Bafadhel M. A multi-centre open-label two-arm 
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COVID-19: study protocol for the ATOMIC2 trial. Trials. 2020 Aug 17; 21(1):718. Doi: 
10.1186/s13063-020-04593-8. 
    


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40. Akram J, Azhar S, Shahzad M, Latif W, Khan KS. Pakistan Randomized and 
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Evaluate 
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(PROTECT) 
of 
Hydroxychloroquine, Oseltamivir and Azithromycin to treat newly diagnosed 
patients with COVID-19 infection who have no comorbidities like diabetes mellitus: 
A structured summary of a study protocol for a randomized controlled trial. Trials. 
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41. Vivas D, Roldán V, Esteve-Pastor MA, Roldán I, Tello-Montoliu A, Ruiz-Nodar JM, 
Cosín-Sales J, Gámez JM, Consuegra L, Ferreiro JL, Marín F; Expert reviewers. 
Recommendations on antithrombotic treatment during the COVID-19 pandemic. 
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COVID-19 pandemic. Position statement of the Working Group on Cardiovascular 
Thrombosis of the Spanish Society of Cardiology].  Rev Esp Cardiol. 2020 
Sep;73(9):749-757. It's Spanish.  Doi: 10.1016/j.recesp.2020.04.006. 
 
42. Rauch B. Cost-effectiveness of rivaroxaban plus aspirin (dual pahtway inhibition) for 
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43. Sophie Testa PPOPRM. Direct oral anticoagulant plasma levels’ striking increase 
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44. Becattini C, Pace U, Rondelli F, Delrio P, Ceccarelli G, Boncompagni M, Graziosi L, 
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Donini A, Bucci AF, Agnelli G. Rivaroxabán for extended antithrombotic prophylaxis 
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45. Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T, Streiff MB, Garcia 
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CASSINI Investigators. Rivaroxabán for Thromboprophylaxis in High-Risk Ambulatory 
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46. Dugina, T.N., Kiseleva, E.V., Chistov, I.V. et al. Receptors of the PAR Family as a Link 
between Blood Coagulation and Inflammation. Biochemistry (Moscow) 67, 65–74 
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CONBIOETICA 09 CIS 012 20 18082.  
 
49. Juan O. Talavera, Rodolfo Rivas-Ruiz.. Clinical research. IV. Relevance of the 
statistical test. Rev Med Inst Mex Safe Soc.2013;51(Supl):S30-34. 
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disease (COVID-19) outbreak. J Autoimmun. 2020 May;109:102433. Doi: 
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the Thrombotic Immune Response Associated to COVID-19 (RITAC). CorSalud 2020 
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52. Schmith VD, Zhou JJ, Lohmer LRL. The Approved Dose of Ivermectin Alone is not the 
Ideal Dose for the Treatment of COVID-19. Clin Pharmacol Ther. 2020 
Oct;108(4):762-765. Doi: 10.1002/cpt.1889. 
53. Suputtamongkol Y, Premasathian N, Bhumimuang K, et al. Efficacy and Safety of 
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doi:10.1371/journal. pntd.0001044 
 


57 
 
 
 
 
 
 
 
 
 
 
 
MEXICAN SOCIAL SECURITY INSTITUTE 
EDUCATION, RESEARCH UNIT 
 AND HEALTH POLICIES 
COORDINATION OF HEALTH RESEARCH 
 
 
INVITATION TO PARTICIPATE IN THE PROTOCOL  
 
 
 
Ihereby extend to you a cordial invitation to participate in this protocol 
entitled "PRONOSTIC MODIFICATION IN PATIENTS WITH COVID-19 
UNDER AN EARLY INTERVENTION TREATMENT IN THE U.M.F 13 
AND U.M.F 20", that you intend that if  you  have positive COVID19  
testing during the onset  of the disease, you will be  given the opportunity 
to receive pharmacological treatment for COVID-19, consideringfor 
your clinical follow-up of the disease the use of video callsvia  "WhatsApp" 
for 14 days, by  medical  personnel, granting   you the benefit if this 
protocol successfully results in an improvement of symptoms and signs of 
COVID-19 disease and thus avoid complications thereof; in the 
same way you are granted these benefits for the whole population that in 
the future suffers from this disease. On the other hand you are 
free to leave treatment for any reason you consider disagreeing to 
remain in protocol. 
   
14. Annexes 
14. Annexes 
Annex 1 


58 
 
 
 
 
 
 
 
 
 
 
 
MEXICAN SOCIAL SECURITY INSTITUTE 
EDUCATION, RESEARCH UNIT 
 AND HEALTH POLICIES 
COORDINATION OF HEALTH RESEARCH 
 
Informed consent letter for participation in research protocols 
(adults) 
 
Study Name: 
PRONOSTIC MODIFICATION IN PATIENTS WITH COVID-19 UNDER EARLY INTERVENTION 
TREATMENT IN U.M.F 13 AND U.M.F 20. 
External Sponsor (if applicable): 
DOESN'T APPLY 
Place and date: 
Family Medicine Unit No. 20, Vallejo Causeway 675 cabbage. Magdalena de las Salinas México 
D.F.  Gustavo.A.Madero Delegation and Family Medicine Unit No. 13, Villa Azcapotzalco between 
Hidalgo and Aztecs, Azcapotzalco Delegation. a____ de_____, 2020. 
Institutional registration number: 
Slope 
Justification and objective of the study:  
Coronavirus, known as SARS-CoV2, is a serious disease in humans and to date there is no approved 
and distributed treatment for its use. In recent months there have been many initiatives to assess 
the capacity of various medicines against SARS-CoV 2. Drugs such as Ivermectin are known for its 
antiparasitic activity, however it has been evaluated in recent years for its activity in laboratory 
studies against various viruses such as yellow fever, among others. This medicinal product has been 
granted in patients with COVID-19 showing considerable benefit however it is recommended to 
perform research protocols with greater confidence in order to consider it for administration. 
Similarly, the well-known antibiotic Azithromycin has shown benefits in COVID-19 patients. The 
drug named Rivaroxaban, is an anticoagulant that also has anti-inflammatory action as well when 
administered in patient COVID-19 has reported a decrease in mortality in patients with COVID-19, 
however it is recommended to perform research protocols to give you greater confidence in its 
administration.  The objective of the study is to evaluate the percentage of patients 
diagnosed with COVID-19 who modify their clinical evolution under a 
comparative treatment of early intervention in rightholders of the U.M.F 13 and U.M.F 
20 of the I.M.S.S., during the period December 2020-February 2021. 
Procedures: 
If you participate in this post-POSITIVE COVID19 study, you will be instructed to take medications 
according to the groups to be handled and will be in accordance with those prescribed by the 
research physician, could be from Group A with taking the following medicines: 
Acetaminophen 500 mg orally 1 tablet every 8 hrs for 3 days in case of fever equal to or greater 
than 38.3oC, Azithromycin tablets of 500 mg will take 1 tablet single dose on the first day and then 
half a tablet (250 mg) orally every 24 for 4 days, Ivermectin 200mcg tablets which will be calculated 
according to your weight and dosage, will be every 24 hrs for 4 days and  Rivaroxaban  tablets of 
Annex 1 


59 
 
10 mg will take 1 every 24 hrs for 10 days. If you have Group  B you will take Paracetamol 500 mg 
orally 1 tablet every 8 hrs for 3 days in case of fever equal to or greater than 38.3oC, Azithromycin 
500 mg tablets will take 1 tablet single dose on the first day and then half a tablet 
orally every 24 for 4 days and Rivaroxaban  10 mg tablets will take 1 every 24 hrs for 10 
days. Also during the taking of medicines and subsequently until 14 days you will be video call daily 
at a time of 10 am to 14 pm, including Saturday and Sunday to know how your clinical symptoms 
are, adverse reactions to drugs related to COVID19, duration of this video call will be approximately 
15 minutes through your cell phone using the video call via WhatsApp. During the first day of your 
participation in the protocol you will be informed to attend IMSS Zone General Hospital No.48 at 
8:30 am, in the laboratory area for the extraction of 5 milliliters blood and perform hematic 
biometrics, C-reactive protein, D-dimer, ferritin, prothrombin time, thromboplastin time and lactic 
dehydrogenase. 
Possible risks and discomfort:  
By participating in this study and taking medications for 14 days you may have allergy to some of 
these medications or some other symptoms such as diarrhea, nausea, vomiting, disorientation, 
dizziness, asthenia, equations, petechiae, vertigo, ringing of ears, intestinal bleeding, angioedema, 
palpitations, hives, chest pain. Upon surveillance by the video call you can report any 
inconvenience and be able to give the handling or indication for second level shipping. 
 
Possible benefits you will receive when 
participating in the study: 
No economic, service or drug benefits will be received outside of the that indicate when you 
participate in this study. By getting adequate results of improvement of symptoms clinicians and 
avoid the complications of patients with COVID19, the benefits will be for the entire population 
that in the future suffers from this disease, the drug can be granted initially in our family medicine 
units. 
Information on treatment results and 
alternatives: 
If during your participation there are also new reports of medicines better than indicated are 
reported or when the request to suspend any for serious effects will also be given the indication of 
immediate suspension to avoid any damage.  
Participation or withdrawal: 
Participation in this study is voluntarily subsequent in providing procedural information, possible 
risks and discomfort. If you decide to participate by signing this informed consent and subsequently 
decide to withdraw you can do so at the time you decide without any impact on the services you 
receive within the IMSS or any retaliation. After the withdrawal in case you decide all the data 
provided and video call will be deleted.  
Privacy and confidentiality: 
The data provided and when the results of this study are published, no information will be given 
that could reveal your identity. Your identity will be protected and hidden. In case you request your 
results it will only be done in a personalized way to protect your identity we will assign you a folio 
number or code and with it you can request your results by appointment. 
Consent Statement: 
After I have read and explained all my doubts about this study: 
 
I do not agree to participate in the study. 
 
If I agree to participate in the study 
 
 
 
 
In case of doubts or clarifications related to the study, please contact: 
Investigator or Responsible Investigator: 
Dr. Gilberto Cruz Arteaga . Clinical Coordinator of Education and Research in Health Enrollment 99351417, 
Enrollment Family Medicine Unit  20. Calzada Vallejo 675 Col. Nueva Vallejo,C.P. 07750 Mayor Gustavo A. 
Madero.,CDMX Tel 53 33 11 00 Ext. 15320 and 15368.                                  E-mail:  gilberto.cruz@imss.gob.mx 
Annex 1


60 
 
Dr. Alma Italia Guerrero Martínez, Clinical Coordinator of Education and Research in Health Enrollment 99368649 
Adscription Family Medicine Unit 13-HGO Villa Azcapotzalco between Hidalgo and Aztecs Del. Azcapotzalco C.P. 
02000 CDMX. Tel 55612700 Ext. 21315 E-mail:  Italia.guerrero@imss.gob.mx 
Collaborators: 
Dr. José Antonio Zamudio González, Holder of the Administrative Operation Body Deconcentrada Norte DF. 
Registration Delegation North Federal  District Av. National Polytechnic Institute No. 5421 Col. Magdalena de las 
Salinas, Del. Gam. C.P. 07760. Tel (55) 5586-2479, (55) 5754-5771, (55) 5747-3500 Ext. 25001 E-mail:  
jose.zamudio@imss.gob.mx 
Dr. Jorge Luis Zendejas Villanueva. Holder of the Head of Medical Services Services. Registration Delegation North 
Federal  District Av. National Polytechnic Institute No. 5421 Building 3 Floor 1. Col. Magdalena de las Salinas, Del. 
Gam. C.P. 07760. Tel 51190990, 57473500 Ext. 52082 E-mail:  jorge.zendejas@imss.gob.mx 
Dr. Elizabeth López Rojas. Planning Coordinator and Institutional Liaison. Registration:98155617. Registration 
Delegation North Federal  District Av. National Polytechnic Institute No. 5421 Building 3 Floor 1. Col. Magdalena 
de las Salinas, Del. Gam. C.P. 07760. Tel. (55) 5747-3500 Ext. 25193 E-mail:  elizabeth.lopez@imss.gob.mx 
In case of doubts or clarifications about your rights as a participant you can contact: Local Committee of Ethics of Health Research of the ICU of the ICS 
of the IMSS: Avenida Cuauhtémoc 330 4th floor Block "B" of the Congress Unit, Colonia Doctors. Mexico City, CP 06720. Phone (55) 56 27 69 00 extension 
21230, email: comiteeticainv.imss@gmail.com 
 
 
 
Name and signature of the participant 
 
 
 
 
 Name and signature of who gets consent 
 
Witness 1 
 
 
 
Name, address, relationship and signature 
 
Witness 2 
 
 
 
Name, address, relationship and signature 
 
Key: 2810-009-013 
 
 
 
 
 


61 
 
 
 
 
MEXICAN SOCIAL SECURITY INSTITUTE 
EDUCATION UNIT, RESEARCH 
AND HEALTH POLICIES 
COORDINATION OF EDUCATION  AND HEALTH  RESEARCH 
Identification format, laboratory  follow-up,  clinical  symptoms and adverse 
reactions 
Date: _______________________ 
A. Demographics 
 
1.1    Number 
 
1.2 Social Security Number  _____________________________________ 
 
1.3Phone. _______________________________________________________ 
 
1.4 Age ________ years    
  
1.5 Sex      
Female  
Male 
 
 
Annex 2 


62 
 
 
 
 
1.6 Marital status. 
Single 
Married 
Free Union 
Widower 
Divorced(a) 
Separated) 
 
1.7 Schooling 
Illiterate 
 
Preschool 
Primary 
Secondary 
High School/ 
High school 
Technical 
career 
Licenciatura Other 
 
1.8 Occupation 
Half-day 
Full day 
Housewife 
Pensioner 
Unemployed  
Other 
 
1.9 Treatment 
Azithromycin/Ribaroxaban/Paracetamol  
0 
Azithromycin/Ivermectin/Ribaroxaban/Paracetamol   
1 
 
1.10 Disease Start Day/ Start Day of Treatment 
Day/month/year 
Day/month/year 
 
 


63 
 
 
1.11 Follow-up 
First Level  
0 
Second level 
1 
Abandonment 
2 
 
B. Laboratory results recorded at the beginning and end of treatment. 
Laboratory tests 
Initial test (values) 
Final test (values) 
Hematic biometrics 
White series 
  
  
Leukocytes 
  
  
Neutrophils 
  
  
Lymphocytes 
  
  
Monocytes 
  
  
Eosinophils 
  
  
Basophils 
  
  
Erythrocytes 
  
  
Red series 
  


64 
 
Hemoglobin 
  
  
Hematocrit 
  
  
Medium corpuscular volume 
  
  
Medium corpuscular hemoglobin 
  
  
Medium haemoglobin concentration 
  
  
RDW 
  
  
Platelets 
  
  
Blood chemistry 
  
  
Glucose 
  
  
Urea 
  
  
Creatinine 
  
  
Liver function tests 
  
  
Old 
  
  
AST 
  
  
DHL 
  
  
Clotting times 
HO CHI MINH CITY 
  
  
TTP 
  
  
INR 
  
  


 
65 
 
C. COVID-19 Symptom Tracking Table 
Symptoms 
Day 0 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Headache 
  
  
  
  
  
  
  
That 
  
  
  
  
  
  
  
Fever 
  
  
  
  
  
  
  
Chest pain 
  
  
  
  
  
  
  
Dyspnea 
  
  
  
  
  
  
  
Conjunctivitis 
  
  
  
  
  
  
  
Myalgias 
  
  
  
  
  
  
  
Arthralgias 
  
  
  
  
  
  
  
Runny nose 
  
  
  
  
  
  
  
Odinophagia 
  
  
  
  
  
  
  
Anosmia 
  
  
  
  
  
  
  
D. Monitoring table for adverse reactions caused by medicines 
Adverse reactions 
Day 0 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Diarrhea 
  
  
  
  
  
  
  
Nausea 
  
  
  
  
  
  
  
Vomiting 
  
  
  
  
  
  
  


 
66 
 
Disorientation 
  
  
  
  
  
  
  
Dizziness 
  
  
  
  
  
  
  
Asthenia 
  
  
  
  
  
  
  
Equimosis/petechiae 
  
  
  
  
  
  
  
Vertigo 
  
  
  
  
  
  
  
Tinnitus 
  
  
  
  
  
  
  
Urticaria 
  
  
  
  
  
  
  
Hemorrhage* 
  
  
  
  
  
  
  
Angioedema* 
  
  
  
  
  
  
  
Palpitations* 
  
  
  
  
  
  
  
Chest pain* 
  
  
  
  
  
  
  
Other 
  
  
  
  
  
  
  
*Symptoms considered as criteria for stopping treatment and follow-up, so it will be suggestedto go 
to second-level hospital. 
 
 
 
 
 
 


 
67 
 
C. COVID-19 symptom monitoring table (continued) 
Symptoms 
Day 7 
Day 8 
Day 9 
Day 10 
Day 11 
Day 12 
Day 13 
Day 14 
Headache 
  
  
  
  
  
  
  
  
That 
  
  
  
  
  
  
  
  
Fever 
  
  
  
  
  
  
  
  
Chest pain 
  
  
  
  
  
  
  
  
Dyspnea 
  
  
  
  
  
  
  
  
Conjunctivitis 
  
  
  
  
  
  
  
  
Myalgias 
  
  
  
  
  
  
  
  
Arthralgias 
  
  
  
  
  
  
  
  
Runny nose 
  
  
  
  
  
  
  
  
Odinophagia 
  
  
  
  
  
  
  
  
Anosmia 
  
  
  
  
  
  
  
  
 D. Adverse reaction monitoring table  (continued) 
Adverse reactions 
Day 7 
Day 8 
Day 9 
Day 10 
Day 11 
Day 12 
Day 13 
Day 14 
Diarrhea 
  
  
  
  
  
  
  
  
Nausea 
  
  
  
  
  
  
  
  
Vomiting 
  
  
  
  
  
  
  
  


 
68 
 
Disorientation 
  
  
  
  
  
  
  
  
Dizziness 
  
  
  
  
  
  
  
  
Asthenia 
  
  
  
  
  
  
  
  
Equimosis/petechiae 
  
  
  
  
  
  
  
  
Vertigo 
  
  
  
  
  
  
  
  
Tinnitus 
  
  
  
  
  
  
  
  
Urticaria 
  
  
  
  
  
  
  
  
Hemorrhage* 
  
  
  
  
  
  
  
  
Angioedema* 
  
  
  
  
  
  
  
  
Palpitations* 
  
  
  
  
  
  
  
  
Chest pain* 
  
  
  
  
  
  
  
  
Other 
  
  
  
  
  
  
  
  
*Symptoms considered as criteria for stopping treatment and follow-up, so it will be suggested to go to 
second-level hospital. 


 
69 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DOUBTS YOU MAY HAVE DURING THE 
COURSE OF THE INTERVIEW 
MEXICAN SOCIAL SECURITY INSTITUTE 
U.M.F No.20 / U.M.F. No.13 
"2020, Year of Leona Vicar, Benemérita Mother of the Fatherland" 
 
 
  
Go to the Emergency Department (H.G.Z. 24/ 
H.G.Z. 48) in the following cases:  
Feeling short of air  
Chest pain 
Confusion  
Increased fever   
"Predicted modification in patients with 
COVID-19 under early intervention treatment 
in U.M.F 13 and U.M.F 20"  
Reports:  
• Dr. Gilberto Cruz Arteaga. Clinical 
Coordinator of Health Education and 
Research.       Enrollment 99351417, 
Family Medicine Unit Enrollment 20.  
Vallejo 675 Col. Nueva Vallejo, C.P. 
07750 Mayor G.A.M., CDMX Tel 
55874422 Ext. 15320 and 15368.  
E-mail:  gilberto.cruz@imss.gob.mx 
 
• Dr. Alma Italia Guerrero Martínez, 
Clinical 
Coordinator 
of 
Health 
Education and Research. Enrollment 
99368649 
Family 
Medicine 
Unit 
Enrollment 
13-HGO. 
Woulda  
Azcapotzalco between Hidalgo and Aztecs  
C.P.02000 Greater Azcapotzalco CDMx. 
Tel 
55612700 
Ext.21315. 
Email:italia.guerrero@imss.gob.mx 
ALARM DATA  
REMEMBER 
 
The follow-up will be carried out specifically by 
the scheduled video calls, in case of any 
symptoms of alarm mentioned above go to the 
emergency rooms of your nearest hospital. 
 
Triptych  
Annex 3 


 
70 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This triptych is in order to clarify some doubts that may 
arise during the course of the interview when being  in 
treatment. 
It is important to note that the interview that is being 
conducted by videocall, is for the purpose of questioning the 
symptomatology that is taken during the days that are beingtreated, 
aimed at improvement or deterioration, or about 
adverse effects related to the consumption of indicated 
medicines. 
If you have any questions, we suggest that you first read 
the questions and answers mentioned in this triptych to 
try to clarify them and not delay the interview time 
focused on symptoms and adverse effects.  
  
Q&A 
1. Is it possible to get COVID-19 by contact with a 
person who does not have any symptoms?  
Yes, it is possible to get a person who has a mild 
cough and does not feel sick. 
 
2. How can we protect ourselves and others if we 
don't 
know 
who 
is 
infected?  
Practice respiratory and hand hygiene at all 
times. Keep at least 1.5 m away between you 
and others, as some infected people may not 
have symptoms or are mild. 
 
3. What to do if my family members have been in close 
contact 
with 
me?  
Close contact means living with someone who has 
the disease, or having been less than 1.5 m away 
from someone who has the disease.  If you 
become ill even with very mild symptoms, such as 
fever and mild pain, you should isolate yourself at 
home, if you do not think you have been exposed 
to COVID-19 but develop these symptoms, isolate 
yourself and monitor your condition. It is more 
likely to infect others in the early stages of the 
disease when you only have mild symptoms. 
4. What does it mean to isolate yourself?  
Isolation occurs when a person who has a fever, 
cough or other symptoms of COVID-19 stays at 
home and does not go to work, school or public 
places, It is necessary to use   the cover at all times. 
5. Can children and adolescents get COVID-19?  
Yes, they have the same chances of becoming 
infected as any other age  group  and spreading 
the disease. However, they are less likely to 
develop a serious illness. 
6. How to properly use a water cover? 
  
  
DOUBTS DURING THE 
INTERVIEW  

ICF_001.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MEXICAN SOCIAL SECURITY INSTITUTE 
EDUCATION, RESEARCH UNIT 
 AND HEALTH POLICIES 
COORDINATION OF HEALTH RESEARCH 
 
Informed consent letter for participation in research protocols 
(adults) 
 
 
Study Name: 
PRONOSTIC MODIFICATION IN PATIENTS WITH COVID-19 UNDER EARLY 
INTERVENTION TREATMENT IN U.M.F 13 AND U.M.F 20 
External Sponsor (if applicable): 
DOESN'T APPLY 
Place and date: 
Family Medicine Unit No. 20, Vallejo Causeway 675 cabbage. Magdalena de las 
Salinas México D.F.  Delegation Gustavo. A.Madero  and Family Medicine Unit No. 
13, Villa Azcapotzalco between Hidalgo and Aztecs, Delegation Azcapotzalco. 
December 11, 2020 
Institutional registration number: 
R-2020-785-176 
Justification and objective of the study:  
Coronavirus, known  as SARS-CoV2,is  a  serious disease in humans and to date there 
is no approved and distributed treatment for its use. In recent months there have been  
many initiatives   toassessthe  capacity of various medicines against SARS-CoV 2. 
Drugs such as  Ivermectin are  known for its antiparasitic activity, however it has been 
evaluated in recent years for its activity in laboratory studies against various viruses 
such as yellow fever, among others. This  medicinal product has been granted in 
patients with COVID-19showing considerable benefit however it is recommended to 
perform research protocols with greater confidence in order to consider it for 
administration. Similarly,  the  well-known antibiotic Azithromycin has shown benefits 
in COVID-19 patients. The  drug with name Rivaroxaban,is ananticoagulant that also 
has anti-inflammatory action as well when administered in patient COVID-19 has 
reported a decrease in mortality in patientswith C OVID-19, however it is 
recommended to perform research protocols to give greater confidence in its 
administration.   The objective of the  study is to evaluate the percentage of patients 
diagnosed with COVID-19 who modify their clinical evolution under a comparative 
treatment of early intervention in rightholders of the U.M.F 13 and U.M.F 20 of the 
I.M.S.S., during the period December 2020- February 2021. 
Procedures: 
If you participate in this study after the positive COVID19 test, you will betold to take 
medicine s according to thegroups youe   handleandwill be according to those 
prescribed by the researchdoctor, it could be Grupo  A with  taking the following 
medicines:  Paracetamol 500 mg orally 1 tablet every 8 hrs  for 3 days in case   of fever 
equal to or greater than 38.3oC, Azithromycin 500 mg tablets will take   1 tablet single 
dose on the first day  and then half a tablet  (250 mg) orally every 24  for 4 days,  
Ivermectin  tablets of 200mcg  which will be  calculated  according to your  pesoand 
dosage,will be  every 24  hrs for 4 days  and Rivaroxaban  tablets of 10 mg will take 1 
every 24  hrs for  10 days. If you have the  Grupo  B  takea  Paracetamol 500 mg via 
oral 1 tablet every 8 hrs for 3 days in case of fever equal to or greater than 38.3oC, 
Azithromycin 500 mg tablets will take 1 tablet single dose on the first day and  
posteriormente half  tablet orally every 24    for 4  days and Rivaroxaban  tablets of 10 
mg will take 1 every 24  hrs for 10days. Also  during the taking of medicines and 
subsequently  until you complete 14 days you will be madea videocall daily at a time of 
10 am to 14 pm, including Saturday and Sunday to know how your clinical symptoms 
are, adverse reactions to drugs related to COVID19, duration of this video callwill 
beapproximately 15 minutes through your cell phone using the video call via  
WhatsApp. During the  first day of your participation in the protocol you will be 
informed to attend IMSS Zone General Hospital No.48 at 8:30 am,  in the laboratory 
area for the extraction of 5 milliliters of blood and perform hematicbiometrics,C-
reactive protein, d-r-D, ferritin, protrombintime, thromboplastin time and lactic 
dehydrogenase.    


 
 
 
 
 
Possible risks and discomfort:  
By participating in this study and taking medications for 14  days you may have allergy 
to some of these medications or some other symptoms such as diarrhea, nausea, 
vomiting, disorientation, dizziness, asthenia, equations, petechiae, vertigo, ringing of 
ears, intestinal bleeding, angioedema, palpitations, hives, chest pain. Upon surveillance 
by the video callyou can reportany  inconvenience and be able to give the handling or 
indication for second level shipping. 
Possible benefits you will receive when 
participating in the study: 
No financial, service or drug benefits will be received outside of those indicated  when 
you  participate in this study. By obtaining adequate clinical symptom improvement 
results and avoiding  complications  of patients with COVID19, the benefits will befor 
the entire population who in the future suffer from thisdisease, the drug may be granted 
initially in our family medicine units. 
Information on treatment results and alternatives: 
If during your participation there are also new reports of medicines better than those 
indicated are reported or when the request to suspend any for serious effects will also be 
given the indication of suspension and nomeans to avoid anydamage. 
Participation or withdrawal: 
Participation in this study is voluntarily subsequent in providing procedural 
information, possible risks and  discomfort. If you decide to participate by signing  this 
informed consent and subsequently decide to withdraw   you can do so at the time you 
decide without  any impact on the services you receive within the IMSS or any 
retaliation. After the withdrawal  in case you decide all the data provided and video call 
will  be deleted. 
Privacy and confidentiality: 
The data provided and when the results of this study are published, no information will be given 
that could reveal your identity. Your identity will be protected and hidden. In case you request 
your results it will only be done in a personalized way to protect your identity we will assign you a 
folio number or code and with it you can request your results by appointment. 
Consent Statement: 
After I have read and explained all my doubts about this study: 
 
I do not agree to participate in the study. 
 
If I agree to  participate in the study 
 
 
 
In case of doubts or clarifications related to the study, please contact: 
Investigator or Responsible Investigator: 
Dr. Gilberto Cruz Arteaga . Clinical Coordinator of Education and Research in Health Enrollment 99351417, 
Enrollment Family Medicine Unit  20. Vallejo 675 Col. Nueva Vallejo, C.P. 07750 Mayor Gustavo  A.  
Madero.,CDMX Tel 53 33 11 00  Ext. 15320 and 15368.                                  E-mail:  
gilberto.cruz@imss.gob.mx 
Dr. Alma Italia Guerrero Martínez, Clinical Coordinator of Education and Research in Health Enrollment 
99368649 Adscription Family Medicine Unit 13-HGO Villa Azcapotzalco between Hidalgo and Aztecs Del. 
Azcapotzalco C.P. 02000 CDMX. Tel 55612700 Ext. 21315 E-mail:  Italia.guerrero@imss.gob.mx 
Collaborators: 
Dr. José Antonio Zamudio González, Holder of the Administrative Operation Body Deconcentrada Norte DF. 
Adscription Delegacion Norte Distrito Federal Av. Instituto Politécnico Nacional No. 5421 Col. Magdalena de 
las Salinas, Del. Gam. C.P. 07760. Tel (55) 5586-2479, (55) 5754-5771, (55) 5747-3500 Ext. 25001 E-mail: 
jose.zamudio@imss.gob.mx 
Dr. Jorge Luis Zendejas Villanueva. Holder of the Head of Medical Services Services. Admission Delegacion 
Norte Distrito Federal Av. National Polytechnic Institute No. 5421 Building 3 Floor 1. Col. Magdalena de las 
Salinas, Del. Gam. C.P. 07760. Tel 51190990, 57473500 Ext. 52082 E-mail: jorge.zendejas@imss.gob.mx 
Dr. Elizabeth López Rojas. Planning Coordinator and Institutional Liaison. Registration:98155617. Admission 
Delegacion Norte Distrito Federal Av. National Polytechnic Institute No. 5421 Building 3 Floor 1. Col. 
Magdalena de las Salinas, Del. Gam. C.P. 07760. Tel. (55) 5747-3500 Ext. 25193 E-mail: 
elizabeth.lopez@imss.gob.mx 
In case of doubts or clarifications about your rights as a participant you can contact: Local Committee of Ethics of Health Research of 
the ICU of the ICS of the IMSS: Avenida Cuauhtémoc 330 4th floor Block "B" of the Congress Unit, Colonia Doctors. Mexico City, CP 06720. Phone 
(55) 56 27 69 00 extension 21230, email:  comiteeticainv.imss@gmail.com 
 
 
Name and signature of the participant 
 
 
 Name and signature of who gets consent 
 
Witness 1 
 
 
 
Witness 2 
 
 


 
 
 
 
 
 
Name, address, relationship and signature 
 
Name, address, relationship and signature 
 
Key: 2810-009-013 
 
 
 
 
 
 
 
 
 
 
 
 
MEXICAN SOCIAL SECURITY INSTITUTE 
EDUCATION, RESEARCH UNIT 
 AND HEALTH POLICIES 
COORDINATION OF HEALTH RESEARCH 
 
 
INVITATION TO PARTICIPATE IN THE PROTOCOL  
 
 
 
Ihereby extend to you a cordial invitation to participate in this 
protocol entitled "PRONOSTIC MODIFICATION IN PATIENTS 
WITH 
COVID-19 
UNDER 
AN 
EARLY 
INTERVENTION 
TREATMENT IN THE U.M.F 13 AND U.M.F 20", that you intend 
that if    you  have positive  COVID19  testing during the onset  of the 
disease, you will be  given the opportunity to receive pharmacological 
treatment for COVID-19, consideringfor your clinical follow-up of the 
disease the use of video callvia  WhatsApp for 14days, by 
medicalpersonnel, granting you the benefit if this protocol successfully 
results in an improvement of symptoms and signs of COVID-19 disease 
and thus avoid complications thereof; in the same way you are granted 
these benefits for the whole population that in the future suffers from 
this disease. On the other hand you are free to leave treatment for any 
reason you consider disagreeing to remain in protocol.