Clinical Trial of Antioxidant Therapy in Patients With Septic Shock

Phase 3

• Conditions: Oxidative Stress; Septic Shock
• Interventions: Drug: Melatonin 5 mg; Drug: Vitamin C 1 GM Oral Tablet; Drug: Vitamin E 400 UNT; Drug: N-acetylcysteine

• Registration Number: NCT03557229
• Lead Sponsor: American British Cowdray Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-05-11
• Study First Submitted QC: 2018-06-13
• Study First Posted: 2018-06-14
• Study Start: 2018-07-23
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-03
• Last Update Posted: 2021-08-10
• Primary Completion: 2022-06
• Study Completion: 2022-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 131

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Melatonin	Melatonin 5 mg	-
Vitamin C	Vitamin C 1 GM Oral Tablet	-
Vitamin E	Vitamin E 400 UNT	-
N-acetylcysteine	N-acetylcysteine	-

Primary Outcome Measures

Name	Time	Method
Organic failure measurement by the Sequential Organ Failure Assessment Score (SOFA)	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.	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Centro Médico ABC; 🇲🇽 Mexico City, Mexico