The Impact of Selective Vitamin D Receptor Activation on Clinical Outcomes in Septic Patients

NCT06209268 | Not Yet Recruiting DMC

• 1 other identifier: USplitSM111
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief Summary

Sufficient serum levels of vitamin D are important for immune system regulation with protective effect against severe infection and overactivated inflammatory response in sepsis. It is also not clear what level of vitamin D in the blood would be the trigger for vitamin D administration. A more selective approach to VDR activation than cholecalciferol could have a more significant role in the clinical outcomes of patients with sepsis. A study demonstrated that low baseline serum level of vitamin D receptor (VDR) was associated with a high incidence of 28-day mortality and negatively correlated with lactate, C-reactive protein, APACHE II SOFA scores, and disease severity among patients with sepsis in an ICU setting. The role of selective vitamin D receptor activation agents (paricalcitol or maxacalcitol) was not studied in septic patients, despite its anti-inflammatory and immunomodulatory properties. Vitamin D analogs have different effects on nuclear VDRs than does calcitriol, through different response elements in various target genes, so it is possible that their effect on a patient with sepsis will be more effective than cholecalciferol. As distribution of VDRs is ubiquitous in many organs and tissues, selective VDR activation with paricalcitol may have beneficial effects in preserving organs functionality and modulating the immune response in sepsis. Hypotheses

1. 1.The immunoregulatory, anti-inflammatory, and anti-oxidative properties of selective vitamin D receptor activator paricalcitol would result in improvement of inflammatory, endothelial function, and antioxidative parameters and clinical outcomes in groups of septic patient admitted to ICU.
2. 2.The baseline septic patient serum 25(OH) D3 levels at admission time in ICU have influence on clinical outcomes as well as on inflammatory, endothelial function, and antioxidative parameters.
3. 3.The inflammatory, endothelial function, and antioxidative parameters measured at ICU admission time have significant impact on clinical outcomes in septic patients.

Conditions

Sepsis

Outcome Measures

Primary Outcomes (1)

• survival (days)

  7. and the 28. day

Secondary Outcomes (33)

• leucocytes count from venous blood specimen

  0. and the 7. day

• blood gasses analysis

  0. and the 7. day

• Oxidative stress

  7.day

• Non-invasive assessments of Arterial Stiffness-pulse wave velocity-pulse wave velocity

  0. and the 7. day

• ultrasound of the spleen (B-mode)

  0. and the 7. day

Study Arms (2)

paricalcitol group

ACTIVE COMPARATOR

Drug: Paricalcitol injection

placebo group

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Paricalcitol injection DRUG

5 μg intravenous paricalcitol (1 mL) per day in five consecutive days

paricalcitol group

Placebo DRUG

0.9% NaCl 1 ml per day in five consecutive days

placebo group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• admitted as sepsis in a medical ICU. The including criteria for sepsis will be defined according The Third International Consensus Definitions for Sepsis and Septic Shock. The sepsis will be defined as suspected infection with SOFA score\>=2.
• The subgroup of participants with septic shock will be defined as sepsis with vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L despite adequate fluid resuscitation.

You may not qualify if:

• total serum calcium ≥2.60 mmol/L,
• significant chronic end stage heart, kidney or liver disease
• active treatment with corticosteroids or cytotoxic drugs
• autoimmune diseases
• malignancies
• cachexia
• previously been on active vitamin D therapy the last four months prior to the study period.

Sponsors & Collaborators

• University of Split, School of Medicine: lead

MeSH Terms

Conditions

Sepsis

Interventions

paricalcitol

Condition Hierarchy (Ancestors)

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

Study Officials

• Vedran Kovacic, prof.dr.

  University of Split, School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vedran Kovacic, prof.dr.

CONTACT

+385915902059; vedran.kovacic.split@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Profesor of Medicine

Study Record Dates

• First Submitted: November 21, 2023
• First Posted: January 17, 2024
• Study Start: May 1, 2025
• Primary Completion: October 1, 2025
• Study Completion: February 1, 2026
• Last Updated: December 6, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share