Effect of Adjunctive Ursodeoxycholic Acid on Oxidative Stress, Inflammation, and Organ Dysfunction in Adults With Sepsis

October 4, 2026 updated by: Khadija Ahmed Mhrose Glal, Tanta University

Effect of Adjunctive Ursodeoxycholic Acid on Oxidative Stress, Inflammation, and Organ Dysfunction in Adults With Sepsis: A Randomized Open-Label, Blinded-Endpoint Trial

epsis is a life-threatening syndrome characterized by acute organ dysfunction resulting from a dysregulated host response to infection. Despite advances in antimicrobial therapy, source control, hemodynamic resuscitation, and organ-supportive strategies, sepsis continues to be associated with substantial morbidity and mortality. Current management is primarily supportive and does not directly target the interconnected processes of excessive inflammation, oxidative stress, endothelial dysfunction, and cellular injury that contribute to progressive organ dysfunction. Current international guidance emphasizes prompt antimicrobial therapy, source control, hemodynamic resuscitation, lactate assessment, and appropriate organ support as the foundation of management.

Oxidative stress is an important component of sepsis pathophysiology. Excessive production of reactive oxygen species, together with impaired endogenous antioxidant defenses, can promote lipid peroxidation, mitochondrial dysfunction, cellular injury, and amplification of inflammatory signaling. Maladaptive activation of inflammatory pathways, including nuclear factor-kappa B (NF-κB), contributes to increased production of pro-inflammatory mediators such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). These processes may contribute to dysfunction of the kidney, liver, lungs, cardiovascular system, and other organs.

Ursodeoxycholic acid (UDCA) is a hydrophilic endogenous bile acid with an established clinical safety record and established hepatobiliary therapeutic use. Beyond its conventional hepatoprotective effects, experimental evidence suggests that UDCA may exert antioxidant, anti-inflammatory, anti-apoptotic, cytoprotective, and mitochondrial effects.

The rationale for investigating UDCA in sepsis is supported by several lines of evidence. Experimental work has demonstrated that UDCA can attenuate sepsis-induced acute kidney injury through activation of the Nrf2/HO-1 antioxidant pathway and inhibition of NF-κB signaling, accompanied by reductions in TNF-α, IL-1β, IL-6, and renal injury markers. Experimental studies have also demonstrated attenuation of sepsis-associated lung injury, pulmonary barrier dysfunction, oxidative stress, inflammatory cytokine production, and PANoptosis following UDCA administration.

Importantly, emerging clinical evidence has begun to investigate UDCA in adult sepsis. A retrospective matched study of critically ill adults with sepsis/septic shock did not demonstrate significant improvement in day-3 SOFA score or vasopressor requirements, although improvement in the PaO₂/FiO₂ ratio and earlier extubation were observed among UDCA recipients. More recently, a small prospective pilot involving eight septic patients receiving UDCA explored its potential effects on sepsis-associated platelet dysfunction, while mechanistic studies implicated TREM2-linked signaling.

Therefore, a randomized controlled trial is warranted to determine whether adjunctive UDCA can modify the biological abnormalities underlying sepsis, particularly oxidative stress and inflammation, and whether these effects are accompanied by improvement in organ dysfunction.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥18 years.
  • Confirmed or strongly suspected bacterial, viral, fungal, or other infectious --disease.
  • Diagnosis of sepsis according to Sepsis-3 criteria.

Exclusion Criteria:

  • Known hypersensitivity to UDCA.
  • Pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: UDCA
Drug: Ursodeoxycholic Acid

Ursodeoxycholic acid 10-15 mg/kg/day
Other: CONTROL

standard medical treatment of sepsis
Drug: Standard medical treatment

placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Absolute change in serum MDA concentration from baseline to day 5.
Time Frame: 7 days
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tanta University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 25, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 1, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 7, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UDCA in Sepsis

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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