Open Clinical Trial of the Use of Antioxidants and Pentoxifylline as Adjuvant Therapy to Standard Therapy in Patients With and Without Septic Shock Secondary to COVID-19 Severe Pneumonia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Stay in an intensive care unit
研究概览
简要总结
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.
详细描述
I. Background
The SARS-CoV-2 virus has a positive-sense RNA, with a genome of approximately 27-32 kb in length. COVID-2019 infection causes severe pneumonia that turns into a pulmonary alveolar collapse within a few hours and leads to the cessation of oxygen exchange. The incubation period for the virus is 2 to 10 days, and the clinical spectrum of the disease ranges from asymptomatic infection to severe respiratory failure. There is elevated lymphopenia, lactate, creatinine, and kinase dehydrogenase, and higher concentrations of interleukins such as IL-1β, IL-5, IL-7, IL-8, IL-9, IL-10, IL-15, IL-12p70, FGF, GCSF, GMCSF, IFNγ, IP10, MCP1, MIP1A, MIP1B, PDGF, TNF-α and VEGF.
There is no treatment for the definitive cure of COVID-19, and there is no vaccine that allows prevention. Considering that the best management choice is to reestablish hemodynamic status, stop organ failure, improve anti-inflammatory conditions, and improve redox status, management strategies could not be randomized since individual conditions change, and patients may have comorbidities at first. The studies that support antioxidant therapy in septic management range from those carried out in vitro, in vivo in an animal model and humans, so the evidence makes it necessary that patients treated with specific antiviral drugs, or antibiotics, receive at the same time nutritional supplement and antioxidants.
The data that support each of the antioxidants as therapy in septic shock are mentioned below.
- N-ACETYL CYSTEINE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Patients with septic shock
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:
- Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours.
- Vitamin E. 800 mg tablet. 800 mg dose every 24 hours.
- Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours.
- 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.
干预措施: Vitamin C (Drug)
Patients with septic shock
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:
- Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours.
- Vitamin E. 800 mg tablet. 800 mg dose every 24 hours.
- Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours.
- 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.
干预措施: Vitamin E (Drug)
Patients with septic shock
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:
- Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours.
- Vitamin E. 800 mg tablet. 800 mg dose every 24 hours.
- Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours.
- 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.
干预措施: Melatonin (Drug)
Patients with septic shock
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:
- Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours.
- Vitamin E. 800 mg tablet. 800 mg dose every 24 hours.
- Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours.
- 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.
干预措施: N-acetyl cysteine (Drug)
Patients with septic shock
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:
- Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours.
- Vitamin E. 800 mg tablet. 800 mg dose every 24 hours.
- Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours.
- 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.
干预措施: Pentoxifylline (Drug)
Patients without septic shock
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:
- Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours.
- Vitamin E. 800 mg tablet. 800 mg dose every 24 hours.
- Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours.
- 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.
干预措施: Vitamin C (Drug)
Patients without septic shock
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:
- Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours.
- Vitamin E. 800 mg tablet. 800 mg dose every 24 hours.
- Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours.
- 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.
干预措施: Vitamin E (Drug)
Patients without septic shock
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:
- Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours.
- Vitamin E. 800 mg tablet. 800 mg dose every 24 hours.
- Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours.
- 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.
干预措施: Melatonin (Drug)
Patients without septic shock
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:
- Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours.
- Vitamin E. 800 mg tablet. 800 mg dose every 24 hours.
- Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours.
- 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.
干预措施: N-acetyl cysteine (Drug)
Patients without septic shock
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:
- Vitamin C. Tablet of 1 gr. A dose of 1 gr every 12 hours.
- Vitamin E. 800 mg tablet. 800 mg dose every 24 hours.
- Melatonin. Tablet 5 mg. A dose of 50 mg every 24 hours.
- 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.
干预措施: Pentoxifylline (Drug)
结局指标
主要结局
Stay in an intensive care unit
时间窗: From admission to discharge, up to 1 week
The number of days of stay in the intensive care unit will be evaluated.
Percentage of patients who required orotracheal intubation
时间窗: From admission to discharge, up to 1 week
The percentage of patients with SARS-COV2 pneumonia in whom orotracheal intubation was avoided will be evaluated.
Death from any cause
时间窗: From admission to discharge, up to 30 days.
It will be evaluated whether secondary to SARS-COV2 pneumonia, the outcome of the patient is dead.
Assisted mechanical ventilation
时间窗: From admission to discharge, up to 1 week
It will be evaluated if it is possible to reduce the days of mechanical ventilation
次要结局
- Evaluation of the total antioxidant capacity(Baseline and 5 days post-dose)
- Measure lipoperoxidation in basal and post-therapy samples(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.)
- Oxidative and antioxidant stress(Baseline and 5 days post-dose)
研究者
Adrian Palacios-Chavarria, MD
Principal investigator
Unidad Temporal COVID-19 en Centro Citibanamex