Clinical Trial of Antioxidant Therapy in Patients With Septic Shock

NCT03557229 | Unknown Phase 3

• 1 other identifier: ABC-18-19
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oxidative Stress; Septic Shock

Keywords

Oxidative Stress; Sepsis; Treatment; Antioxidant therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Nitrates and nitrites levels

  Immediately before treatment and 48 hours after therapy

• Malondialdehyde levels

  Immediately before treatment and 48 hours after therapy

• Total antioxidant capacity

  Immediately before treatment and 48 hours after therapy

• Glutathione Peroxidase Enzyme Activity

  Immediately before treatment and 48 hours after therapy

• Glutathione S-transferase Activity

  Immediately before treatment and 48 hours after therapy

Other Outcomes (5)

• TNF-α

  Immediately before treatment and 48 hours after therapy

• IL-1

  Immediately before treatment and 48 hours after therapy

• IL-6

  Immediately before treatment and 48 hours after therapy

Study Arms (5)

Melatonin

EXPERIMENTAL

Drug: Melatonin 5 mg

Vitamin C

EXPERIMENTAL

Drug: Vitamin C 1 GM Oral Tablet

Vitamin E

EXPERIMENTAL

Drug: Vitamin E 400 UNT

N-acetylcysteine

EXPERIMENTAL

Drug: N-acetylcysteine

Control

NO INTERVENTION

Interventions

Melatonin 5 mg DRUG

Oral: 50 mg once daily for 5 days

Melatonin

Vitamin C 1 GM Oral Tablet DRUG

Oral: 1 GM every 6 hours for 5 days

Vitamin C

Vitamin E 400 UNT DRUG

Oral: 400 UNT every 8 hours for 5 days

Vitamin E

N-acetylcysteine DRUG

Oral: 1200 mg every 12 hours for 5 days

N-acetylcysteine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• American British Cowdray Medical Center: lead

Study Sites (1)

Centro Médico ABC

Mexico City, 05300, Mexico

Location

Related Publications (1)

• Aisa-Alvarez A, Perez-Torres I, Guarner-Lans V, Manzano-Pech L, Cruz-Soto R, Marquez-Velasco R, Casarez-Alvarado S, Franco-Granillo J, Nunez-Martinez ME, Soto ME. Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System. Cells. 2023 May 6;12(9):1330. doi: 10.3390/cells12091330.

  PMID: 37174730 DERIVED

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Melatonin; Acetylcysteine

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Alfredo Aisa Alvarez, MD

  American British Cowdray Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 11, 2018
• First Posted: June 14, 2018
• Study Start: July 23, 2018
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: August 10, 2021

Record last verified: 2021-08

Locations

ME (1)