Clinical Trial of Antioxidant Therapy in Patients With Septic Shock

Study Overview
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Brief Summary
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Sepsis and septic shock are public health problems worldwide that represents an excessive cost for health systems. Despite the great technological and research advances, mortality can reach up to 80% in patients with multiple organ failure (FOM). Therapeutic studies focused on evaluating the usefulness of the use of antioxidants have shown different outcomes and results. This randomized clinical trial in patients with septic shock at two general intensive care units try to evaluate the usefulness of four different antioxidant therapies added to the conventional treatment, which includes: n-acetyl cysteine, vitamin C, vitamin E and melatonin. Measurement of parameters before and after treatment of oxidative stress includes nitrates and nitrites, lipid peroxidation, glutathione peroxidase, glutathione s transferase, extracellular activity of SOD, GSH concentration and evaluation of total antioxidant capacity. The investigators will also evaluate the clinical impact of antioxidant therapy with the SOFA score.

Official Title
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Randomized Controlled Clinical Trial of Antioxidant Therapy in Critically Ill Patients With Septic Shock: Analysis Before and After Treatment of the Oxidative Stress

Conditions
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Oxidative Stress, Septic Shock

Intervention / Treatment
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* Drug: Melatonin 5 mg
* Drug: Vitamin C 1 GM Oral Tablet
* Drug: Vitamin E 400 UNT
* Drug: N-acetylcysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of septic shock in the last 24 hours characterized by refractory hypotension and vasopressor requirement despite sufficient fluid resuscitation (20 mL/kg of colloids or 40 mL/kg of crystalloids) to maintain a blood pressure ≥ 65 mmHg with a lactate> 2 mmol/L. Admitted to the ICU of the ABC Medical Center. Give informed consent. Exclusion Criteria: Patients who refuse to be included. Chronic or recent use of steroids. Use of statins. Patients receiving some type of antioxidant treatment. Any contraindication to the use of vitamin C, vitamin E, n-acetylcysteine or melatonin. Pregnant women.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin<br> | Drug: Melatonin 5 mg<br>* Oral: 50 mg once daily for 5 days<br>|
| Experimental: Vitamin C<br> | Drug: Vitamin C 1 GM Oral Tablet<br>* Oral: 1 GM every 6 hours for 5 days<br>|
| Experimental: Vitamin E<br> | Drug: Vitamin E 400 UNT<br>* Oral: 400 UNT every 8 hours for 5 days<br>|
| Experimental: N-acetylcysteine<br> | Drug: N-acetylcysteine<br>* Oral: 1200 mg every 12 hours for 5 days<br>|
| No Intervention: Control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Organic failure measurement by the Sequential Organ Failure Assessment Score (SOFA) | The SOFA score is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). The worst physiological variables is collected serially every 24 hours of a patient's ICU admission. The worst measurement is defined as the measure that correlated to the highest number of points. The SOFA score ranges from 0 to 24. The investigators are going to evaluate the daily total score and the trend before and after the administration of the therapy. | Up to 7 days (1 week). From date of randomization and every 24 hours until discharge from the intensive care unit or date of death from any cause, whichever came first, assessed up to 7 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nitrates and nitrites levels | Oxidative stress | Immediately before treatment and 48 hours after therapy | 
| Malondialdehyde levels | Lipid peroxidation | Immediately before treatment and 48 hours after therapy | 
| Total antioxidant capacity | Antioxidant status | Immediately before treatment and 48 hours after therapy | 
| Glutathione Peroxidase Enzyme Activity | Antioxidant status | Immediately before treatment and 48 hours after therapy | 
| Glutathione S-transferase Activity | Antioxidant status | Immediately before treatment and 48 hours after therapy | 
| Extracellular Superoxide Dismutase Activity | Antioxidant status | Immediately before treatment and 48 hours after therapy | 
| Glutathione concentration | Antioxidant status | Immediately before treatment and 48 hours after therapy | 
| Selenium | Antioxidant status | Immediately before treatment and 48 hours after therapy | 
| Vitamin C | Antioxidant status | Immediately before treatment and 48 hours after therapy | 
| Thioredoxin | Antioxidant status | Immediately before treatment and 48 hours after therapy | 
| Carbonylation | Pro-oxidant status | Immediately before treatment and 48 hours after therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oxidative Stress, Sepsis, Treatment, Antioxidant therapy