Effect of a NSS to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III

Study Overview
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Brief Summary
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The disease caused by SARS-CoV-2, has derived a pandemic in which its evolution and complications depend on the immune capacity of the host. The virus has been characterized by presenting an inflammatory cascade, increased by the overproduction of proinflammatory cytokines, the decrease in metalloenzymes and also the rapid spread of the virus. There are several lines of treatment, however, nutritional treatment only considered a caloric intake. For this reason, this study will evaluate the evolution of patients with COVID-19 assisted by nutritional support system and the effect of this therapy in reducing complications and comorbidities. Research question: Will the nutritional support system reduce complications in stage III positive COVID-19 patients with comorbidities (type 2 DM, SAH, overweight / obesity with BMI <35), with a better benefit than that achieved with the conventional nutritional treatment ?. Hypothesis: The nutritional support system will reduce the complications of patients with COVID-19 in stage III with comorbidities. General Objective: To determine the effect of the use of a nutritional support system on complications in patients with COVID-19 in stage III with comorbidities. Methodology: A controlled, blinded, randomized clinical trial will be conducted in patients with COVID-19, hospitalized at the ISSEMYM Toluca Arturo Montiel Rojas Medical Center, who meet the inclusion criteria. The evolution of the group of patients receiving the nutritional support system (NSS) and the normal diet implemented by the hospital will be evaluated against the group of patients receiving only the diet, using clinical examination, laboratory and cabinet tests during their hospital stay. Statistical analysis: for independent groups with normal distribution, Student's T will be applied. If the distribution does not meet normality criteria, a Mann Whitney U will be performed; Two-way ANOVA will be applied to monitor the groups over time with normal distribution. If the distribution does not meet normality criteria, a Friedman test will be performed, in both cases post hoc tests will be performed. The results will be analyzed using version 6 of the Graphpad Prism software.

Detailed Description
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Patients in the COVID-19 area, who are treated at the ISSEMYM Toluca Arturo Montiel Rojas Medical Center, located in Paseo Tollocan, Av. Baja Velocidad km 575, Barrio de Sta Clara, Toluca de Lerdo, México; both sexes, with the presence of comorbidities (type 2 DM, SAH, overweight or obesity BMI <35) and in stage III of the disease. Consecutive cases. With systematic randomized allocation using a sequence of random numbers built with the Excel program divided into two groups. Once the participants of the COVID-19 area have been selected, patients and / or family members will be spoken to to explain the protocol and obtain the signatures of the letters of informed consent. Assignment to the research group will be carried out randomly. Once the patients have been admitted to the study, the following will be carried out: test of COVID-19 by means of PCR, thorax tomography, complete clinical history, Mini Nutritional Assessment (MNA), food diary, list of clinical variables designed by us, complete blood count, coagulation profile, serum electrolytes, blood chemistry (6-elements), lipidic profile, liver function tests, ferritin, fibrinogen, C-reactive protein, procalcitonin and D-dimer. Anthropometric measurements will also be carried out (height, weight, BMI, muscle mass %, fat % and visceral fat%). The follow-up will be carried out daily for 21 days or earlier, if they are discharged from the hospital due to improvement in the evolution, at that moment the patient concludes the study. The following points will be supervised, recording the information in files and photos, since the hospital security protocol does not allow to extract stationery from the COVID-19 area: Application and consumption of NSS supplementation as appropriate. Morning and evening vital signs. Daily clinical evaluation (It includes variables such as oxygen flow, activity level, integrity of the hair, skin and nails, evaluation of the sense of taste and smell, pain, gastrointestinal symptoms, bowel movements, prescribed medications, mood, among others). Anthropometric measurements using a scale every 2 days (only if the patient is stable and can maintain balance). Food diaries of each patient. Laboratory studies every 3 days (previously mentioned). In the same way, the following will be taken into account: the number of days hospitalized, number of patients who progress to ventilation, number of patients who die, number of patients who are extubated and number of days after extubation. A descriptive analysis will be carried out for each continuous variable. These variables will be expressed as mean ± standard deviation and standard error. It will be done according to the distribution of the data; For independent groups with a normal distribution, Student's T will be applied. If the distribution does not meet normality criteria, a Mann Whitney U will be performed; For the follow-up of dependent groups with normal distribution, two-way ANOVA will be applied. If the distribution does not meet normality criteria, a Friedman test will be performed, in both cases post hoc tests will be performed, taking into account that a significant value of p of < 0.05. The results will be analyzed using version 6 of the Graphpad Prism software.

Official Title
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Effect of a Nutritional Support System to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III

Conditions
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COVID19, Diabetes Mellitus, Hypertension, Obesity, Overweight, Oxygen Saturation, Mortality, Inflammation

Intervention / Treatment
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* Dietary Supplement: Nutritional support system (NSS)
* Other: Conventional nutritional support designed by hospital nutritionists


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted to the ISSEMYM Toluca Medical Center Arturo Montiel Rojas , diagnosed with COVID-19 confirmed by PCR. Patients in need of supplemental O2 with nasal prongs or reservoir-mask for satO2 <90% and respiratory distress. With concomitant diseases such as cardiovascular disease, diabetes mellitus 2, hypertension, overweight or obesity BMI <35. Both sexes. Over 30 years old. The patient tolerate oral feeding. Signing of the letter of informed consent. Exclusion Criteria: Detachment from treatment. Admission to the ICU for any reason. Patients who do not tolerate the oral route. Reactions to treatment that compromise the health of patients.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: exploratory study, it is a controlled, blinded, randomized clinical trial design.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: control group<br>Patients who received the standard diet | Other: Conventional nutritional support designed by hospital nutritionists<br>* Diet designed by the nutrition department according to comorbidities and intubation probability. Food will be established according to the provisions of the ISSEMYM Toluca Arturo Montiel Rojas Medical Center.<br>|
| Experimental: Intervention group<br>Patients who received the nutritional support system (NSS) and the standard diet | Dietary Supplement: Nutritional support system (NSS)<br>* Combination of three B vitamins (B1, B6 and B12) Neurobion 10 mg solution for IM injection, One every 24 hours for the first 5 days. Probiotics Saccharomyces boulardii CNCM I-745 Floratil. One morning and one evening 250 mg capsule during the first 6 days One envelope of NSS-1 in the morning and one envelope in the afternoon mixed with 400 ml of water each, contain nutritional support system.<br>Other: Conventional nutritional support designed by hospital nutritionists<br>* Diet designed by the nutrition department according to comorbidities and intubation probability. Food will be established according to the provisions of the ISSEMYM Toluca Arturo Montiel Rojas Medical Center.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival, the total number of patients included in the study and completed a 40-day follow-up. | 40 days. | 
| Overall Mortality at Day 40 | Total number of patients who died before day 40 of follow-up. | 40 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival in Intubated Patients at Day 40 | Total number of patients who were intubated, extubated, discharged and completes the 40 day follow-up | 40 days | 
| Mortality in Intubated Patients at Day 40 | Patients who were intubated during their hospital stay and died before completing follow-up on day 40. | 40 days | 
| Progression to Mechanical Ventilation Assistance | total number of patients included in the study who progressed to mechanical ventilation during the first 10 days of hospital stay. | 10 days. | 
| Participants With Normal Bristol Scale at Day 3 | The Bristol Stool Form Scale categorizes stools into one of seven stool types ranging from type 1 (hard lumps) to type 7 (watery diarrhea). Type 3 and 4 were considered Normal. | day 3 | 
| Hidric Balance on Day 3 | The ratio between the water assimilated into the body and that lost from the body, in milliliters. | It is evaluated on day 3 of hospital stay (duration approximately 10 minutes). | 
| Oxigen Saturation >90% on Day 3 | the total number of patients with oxygen saturation >90% on day 3 of their hospital stay. | day 3. | 
| PHQ-9 Test | Is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders, includes 9 items, which evaluate the presence of depressive symptoms based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders version 4, during the last 2 weeks, how often the patient presented depressive symptoms. According to the sum of the score obtained, the following 4 categories will be considered: 0-4 minimum existence or absence of depressive symptoms; 5-9 = mild depressive symptoms; 10-14 = moderate depressive symptoms; 15-19 = moderate to severe depressive symptoms; 20-27 = severe depressive symptoms. | baseline and hospital discharge | 
| Oxigen Flow (Intragroup) | Difference in oxygen delivery between the baseline period and day 3 of hospital stay in each group. | baseline and day 3 | 
| qSOFA at Day 3 | Quick-Sequential Organ Failure Assessment (qSOFA) score gives 0 to 3 points. ≥2 in the setting of suspected infection had a high predicted in-hospital mortality rate and could be considered septic. | Baseline and Day 3 | 
| Number of Defectations on Day 3 | Refers to the subjective sensation of increased abdominal pressure without an increase in abdominal size, the number of defecations were quantified at day 3 and compared between both groups. | Day 3 | 
| Number of Participants With Distension on Day 3 | Is a visible increase in abdominal girth.1. Present, 2. Absent. | Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID19, Nutritional support, SARS-COV-2, Pneumonia, Supplementation, Probiotics