Clinical Trial of Antioxidant Therapy in Patients With Septic Shock

Sponsor
American British Cowdray Medical Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03557229
Collaborator
(none)
131
1
5
46.3
2.8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
131 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Randomized Controlled Clinical Trial of Antioxidant Therapy in Critically Ill Patients With Septic Shock: Analysis Before and After Treatment of the Oxidative Stress
Actual Study Start Date :
Jul 23, 2018
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Jun 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Melatonin

Drug: Melatonin 5 mg
Oral: 50 mg once daily for 5 days

Experimental: Vitamin C

Drug: Vitamin C 1 GM Oral Tablet
Oral: 1 GM every 6 hours 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

No Intervention: Control

Outcome Measures

Primary Outcome Measures

  1. 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

  1. Nitrates and nitrites levels [Immediately before treatment and 48 hours after therapy]

    Oxidative stress

  2. Malondialdehyde levels [Immediately before treatment and 48 hours after therapy]

    Lipid peroxidation

  3. Total antioxidant capacity [Immediately before treatment and 48 hours after therapy]

    Antioxidant status

  4. Glutathione Peroxidase Enzyme Activity [Immediately before treatment and 48 hours after therapy]

    Antioxidant status

  5. Glutathione S-transferase Activity [Immediately before treatment and 48 hours after therapy]

    Antioxidant status

  6. Extracellular Superoxide Dismutase Activity [Immediately before treatment and 48 hours after therapy]

    Antioxidant status

  7. Glutathione concentration [Immediately before treatment and 48 hours after therapy]

    Antioxidant status

  8. Selenium [Immediately before treatment and 48 hours after therapy]

    Antioxidant status

  9. Vitamin C [Immediately before treatment and 48 hours after therapy]

    Antioxidant status

  10. Thioredoxin [Immediately before treatment and 48 hours after therapy]

    Antioxidant status

  11. Carbonylation [Immediately before treatment and 48 hours after therapy]

    Pro-oxidant status

Other Outcome Measures

  1. TNF-α [Immediately before treatment and 48 hours after therapy]

    Inflammatory Response Pathway

  2. IL-1 [Immediately before treatment and 48 hours after therapy]

    Inflammatory Response Pathway

  3. IL-6 [Immediately before treatment and 48 hours after therapy]

    Inflammatory Response Pathway

  4. Ionized Ca2+ [Immediately before treatment and 48 hours after therapy]

    Electrolytes

  5. Ionized Mg2+ [Immediately before treatment and 48 hours after therapy]

    Electrolytes

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Centro Médico ABC Mexico City Mexico 05300

Sponsors and Collaborators

  • American British Cowdray Medical Center

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Alfredo Aisa Alvarez, Principal Investigator, American British Cowdray Medical Center
ClinicalTrials.gov Identifier:
NCT03557229
Other Study ID Numbers:
  • ABC-18-19
First Posted:
Jun 14, 2018
Last Update Posted:
Aug 10, 2021
Last Verified:
Aug 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
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
Keywords provided by Alfredo Aisa Alvarez, Principal Investigator, American British Cowdray Medical Center
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 10, 2021