Clinical Trial of Antioxidant Therapy in Patients With Septic Shock

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Septic Shock; Oxidative Stress
• Intervention / Treatment: Drug: Melatonin 5 mg; Drug: Vitamin C 1 GM Oral Tablet; Drug: Vitamin E 400 UNT; Drug: N-acetylcysteine

• Study Type: Interventional
• Enrollment (Anticipated): 131
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 05300
    • Centro Médico ABC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control
EXPERIMENTAL: Vitamin C	Drug: Vitamin C 1 GM Oral Tablet; Oral: 1 GM every 6 hours for 5 days
EXPERIMENTAL: Melatonin	Drug: Melatonin 5 mg; Oral: 50 mg once daily for 5 days
EXPERIMENTAL: Vitamin E	Drug: Vitamin E 400 UNT; Oral: 400 UNT every 8 hours for 5 days
EXPERIMENTAL: N-acetylcysteine	Drug: N-acetylcysteine; Oral: 1200 mg every 12 hours for 5 days

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
TNF-α	Inflammatory Response Pathway	Immediately before treatment and 48 hours after therapy
IL-1	Inflammatory Response Pathway	Immediately before treatment and 48 hours after therapy
IL-6	Inflammatory Response Pathway	Immediately before treatment and 48 hours after therapy
Ionized Ca2+	Electrolytes	Immediately before treatment and 48 hours after therapy
Ionized Mg2+	Electrolytes	Immediately before treatment and 48 hours after therapy

Collaborators and Investigators

• Sponsor: American British Cowdray Medical Center
• Investigators: Principal Investigator: Alfredo Aisa Alvarez, MD, American British Cowdray Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 23, 2018
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2022

Study Registration Dates

• First Submitted: May 11, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (ACTUAL): June 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 10, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Treatment; Oxidative Stress; Sepsis; Antioxidant therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Antiviral Agents; Protective Agents; Micronutrients; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Melatonin; Vitamin E; Vitamins; Acetylcysteine; N-monoacetylcystine; Ascorbic Acid
• Other Study ID Numbers: ABC-18-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No