Antioxidants as Adjuvant Therapy to Standard Therapy in Patients With COVID-19

NCT04570254 | Completed DMC

• 1 other identifier: 09-CEI-011-20160627
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: SARS-CoV2 infection produces severe pneumonia with pulmonary alveolar collapse. There is no specific treatment to date. In experimental models and humans with septic shock, there is a high production of nitric oxide (NO) and reactive nitrogen species (RNS) and can cause multiple organ failure. The administration of antioxidants such as n-acetylcysteine (NAC), vitamin C, melatonin, and vitamin E participate in increasing the intracellular content of GSH, ROS sequestration, protection of the lipids of cell membranes, cytosol proteins, nuclear DNA, mitochondrial and decrease LPO. Justification: as there is no specific antiviral therapy, the therapeutic options are limited, complications and mortality are high; It is intended to evaluate the effect of antioxidants on the storm outcome of the dysregulation of oxidative stress. Hypothesis: It is postulated that adjuvant therapy with antioxidants and Pentoxifylline reduces the use of ventilators in patients with or without septic shock secondary to severe SARS-COV2 pneumonia as decreases lipoperoxidation, and corrects dysregulation of oxidative stress by increasing the antioxidant capacity. Objectives: To evaluate whether it is possible to avoid intubation or decrease assisted mechanical ventilation days, improve oxidative stress dysregulation in patients with SARS-COV2 infection with severe pneumonia with or without septic shock. Methodology: Quasi-experimental, open analytical, prospective, and longitudinal study (before-after). In patients over 18 years of age who are admitted to the CITIBANAMEX Center with or without septic shock secondary to severe SARS-COV2 pneumonia. There will be two groups: 1) patients without septic shock and 2) patients with septic shock secondary to severe pneumonia due to SARS-COV2. A single antioxidant will be applied following the clinical decision tree (NAC, Vit C, Vit E, melatonin) more Pentoxifylline orally or by orogastric tube for a total of 5 days from the start of the protocol. APACHE II will calculate the risk, SOFA, MEXSOFA, measurements of IL-8, vitamin C, NO3 / NO2, LOP, total antioxidant capacity will be carried out at baseline and 48 hours. SOFA will be calculated for seven days, in addition to days of hospitalization, days of mechanical ventilation. It was evaluated 28 days after discharge by telephone.

Conditions

Pneumonia, Viral; Covid19; ARDS; Oxidative Stress

Keywords

SARS-COV2; Pneumonia; ARDS; Antioxidants

Outcome Measures

Primary Outcomes (4)

• Death from any cause

  It will be evaluated whether secondary to SARS-COV2 pneumonia, the outcome of the patient is dead.

  From admission to discharge, up to 30 days.

• Percentage of patients who required orotracheal intubation

  The percentage of patients with SARS-COV2 pneumonia in whom orotracheal intubation was avoided will be evaluated.

  From admission to discharge, up to 1 week

• Assisted mechanical ventilation

  It will be evaluated if it is possible to reduce the days of mechanical ventilation

  From admission to discharge, up to 1 week

• Stay in an intensive care unit

  The number of days of stay in the intensive care unit will be evaluated.

  From admission to discharge, up to 1 week

Secondary Outcomes (5)

• Measure lipoperoxidation in basal and post-therapy samples

  Baseline and 5 days post-dose

• Evaluation of the total antioxidant capacity

  Baseline and 5 days post-dose

• Oxidative and antioxidant stress

  Baseline and 5 days post-dose

• Effect of antioxidant therapy at the level on organ failure secondary to SARS-COV2

  From day 0 to day 7 post antioxidant dose.

• Effect of antioxidant therapy at the level on organ failure secondary to SARS-COV2

  From day 0 to day 7 post antioxidant dose.

Study Arms (2)

Patients with septic shock

EXPERIMENTAL

Only one antioxidant will be administered, which the treating physician will decide following a previously established decision tree plus pentoxifylline via an oral or orogastric tube for five days. With the following specifications: 1. Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours. 2. Vitamin E. 800 mg tablet. 800 mg dose every 24 hours. 3. Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours. 4. N-acetylcysteine. Tablet 600 mg. 600 mg dose every 12 hours. The dose of pentoxifylline that all patients will receive is as follows: a) Pentoxifylline. 400 mg tablets. 400 mg dose every 12 hours.

Drug: Vitamin C; Drug: Vitamin E; Drug: Melatonin; Drug: N-acetyl cysteine; Drug: Pentoxifylline

Patients without septic shock

EXPERIMENTAL

Only one antioxidant will be administered, which the treating physician will decide following a previously established decision tree plus pentoxifylline via an oral or orogastric tube for five days. With the following specifications: 1. Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours. 2. Vitamin E. 800 mg tablet. 800 mg dose every 24 hours. 3. Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours. 4. N-acetylcysteine. Tablet 600 mg. 600 mg dose every 12 hours. The dose of pentoxifylline that all patients will receive is as follows: a) Pentoxifylline. 400 mg tablets. 400 mg dose every 12 hours.

Drug: Vitamin C; Drug: Vitamin E; Drug: Melatonin; Drug: N-acetyl cysteine; Drug: Pentoxifylline

Interventions

Vitamin C DRUG

Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours. Dissolve one tablet in a volume of 30 ml of water and administer it immediately, then rinse the glass with 10 ml of water and administer it to the patient. Protect from light at all times, as it is photosensitive.

Also known as: Antioxidant option 1

Patients with septic shock; Patients without septic shock

Vitamin E DRUG

Vitamin E. 800 mg tablet. 800 mg dose every 24 hours. Dissolve the capsule in 30 ml of hot water. The administration of vitamin E is recommended during or after meals since its absorption depends on pancreatic enzymes' presence.

Also known as: Antioxidant option 2

Patients with septic shock; Patients without septic shock

Melatonin DRUG

Melatonin Tablet 5 mg. A dose of 50 mg every 24 hours. Grind the 10 5 mg melatonin tablets (50 mg), levitate with 50 mL of Ora-plus (Transferring to a beaker with a magnetic stirrer). Maintain gentle agitation. "Rinse" the mortar with 10 mL of Ora-sweet. Add 30 mL of Ora sweet to the glass where the mixture is being made. Makeup with Ora-sweet cbp 100 mL Place label FL02 with legend Melatonin 50 mg / 20 mL. Protected from light (Dispense in a black bag that covers the transparent bag of the preparation)'s primary packaging) Give after breakfast.

Also known as: Antioxidant option 3

Patients with septic shock; Patients without septic shock

N-acetyl cysteine DRUG

N-acetylcysteine. Tablets, 600 mg. 600 mg dose every 12 hours. Dissolve one tablet in a volume of 30 ml of water and administer it immediately, then rinse the glass with 10 ml of water and administer it to the patient.

Also known as: Antioxidant option 4

Patients with septic shock; Patients without septic shock

Pentoxifylline DRUG

Pentoxifylline. 400 mg tablets. 400 mg dose every 12 hours. The tablet is dissolved in 30 ml of water and is administered orally or nasogastric tube.

Also known as: Pentofifylline ER

Patients with septic shock; Patients without septic shock

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted to the UTC in the Temporary COVID-19 Citibanamex Center with suspected or diagnosed severe pneumonia due to SARS-COV2 with or without septic shock.
• Patients who accept and sign informed consent. If the patient is clinically unable to authorize, acceptance by a first-degree relative will be requested.
• Diagnosis of septic shock in the last 24 hours characterized by refractory hypotension and vasopressor requirement despite adequate fluid resuscitation (20 mL/kg of colloids or 40 mL/kg of crystalloids) to maintain a blood pressure ≥ 65 mmHg with lactate\> two mmol / L.

You may not qualify if:

• Patients with an advance directive format.
• Chronic use of steroids in the past six months or recent.
• Use of statins before admission.
• Patients who are under some antioxidant treatment.
• Any contraindication for the use of Vit C, Vit E, NAC, and melatonin.
• Pregnant women.

Sponsors & Collaborators

• Unidad Temporal COVID-19 en Centro Citibanamex: lead
• Instituto Nacional de Cardiologia Ignacio Chavez: collaborator
• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: collaborator

Study Sites (1)

Unidad Temporal COVID-19 en Centro Citibanamex

Mexico City, 11200, Mexico

Location

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MeSH Terms

Conditions

Pneumonia, Viral; COVID-19; Pneumonia

Interventions

Ascorbic Acid; Vitamin E; Melatonin; Acetylcysteine; Pentoxifylline

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Virus Diseases; Lung Diseases; Respiratory Tract Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indoles; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins; Theobromine; Xanthines; Purinones; Purines

Study Officials

• Maria Elena Soto Lopez, PhD

  mesoto50@hotmail.com

  STUDY DIRECTOR

• Adrián Palacios Chavarria, MD

  Unidad Temporal COVID-19 en Centro Citibanamex

  PRINCIPAL INVESTIGATOR

• José Guillermo Domínguez Cherit, MD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: They will be blinded to the patient's treatment, the patient or participant, the investigator, and the outcome assessor. You will only receive the participant number during the analysis. The care provider will not be blinded; they will know which antioxidant plus pentoxifylline the patient will receive; however, they will not have access to the results until the clinical trial is concluded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: septic shock and without septic shock will be divided into two groups. An antioxidant will be administered orally or by orogastric tube (vitamin C, melatonin, n-acetylcysteine, vitamin E) plus pentoxifylline. Following a decision tree that the treating physician will follow.

Study Record Dates

• First Submitted: September 26, 2020
• First Posted: September 30, 2020
• Study Start: August 19, 2020
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: May 21, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)