Vitamin D Status in Patients With Severe Sepsis

NCT02684487 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: ViDISS_temp
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is a clinical entity that complicates infection. Without early recognition and timely management, it can rapidly progress to severe sepsis, septic shock, and culminate in multiple organ dysfunction syndrome. Forty to 70% of septic patients have low vitamin D status, yet little is known about the impact of vitamin D3 (vitD3) supplementation in this patient population. As such, the investigators propose a randomized, double-blinded, placebo-controlled trial to test the hypothesis that early, rapid correction of low vitamin D status, as an adjunct to established treatment guidelines, will improve clinical outcomes and measurably alter immune profile in patients with severe sepsis.

Conditions

Sepsis; Severe Sepsis; End Organ Damage; Multi Organ Failure

Keywords

vitamin D; vitamin D3; sepsis; severe sepsis; critical illness; ICU

Outcome Measures

Primary Outcomes (1)

• 90 day mortality

  90 day mortality will be assessed in patients included in the study

  90 day mortality

Secondary Outcomes (4)

• Serum b25OHD: Baseline serum b25OHD and serum b25OHD after intervention, until hospital day 5

  24h of severe sepsis onset until hospital day 5

• Serum measurement of AMPs, cathelicidin, and B-defensin: Baseline serum AMPs, cathelicidin, and B-defensin and AMPs, cathelicidin, and B-defensin after intervention, until hospital day 5

  24h of severe sepsis onset until hospital day 5

• Serum measurement of cytokines: Baseline serum cytokines and serum cytokines after intervention, until hospital day 5

  24h of severe sepsis onset until hospital day 5

• sequential organ failure assessment scores in the first 5 day after severe sepsis onset

  24h of severe sepsis onset until hospital day 5

Study Arms (2)

vitamin D3

ACTIVE COMPARATOR

Patients will be given single dose of vitamin D3 within 24 hours of new-onset severe sepsis, followed by weekly doses of vitD3 (25,000 IU) up to 90 days to assess clinical outcomes and key biomarkers.

Drug: vitamin D3

Placebo

SHAM COMPARATOR

Patients will be given placebo intervention within 24 hours of new onset severe sepsis followed by or placebo for up to 90 days to assess clinical outcomes and key biomarkers.

Drug: Placebo

Interventions

vitamin D3 DRUG

Patients will be given 400,000 IU of vitamin D3 within 24 hours of severe sepsis onset followed by weekly doses of 25,000 IU until 90 days or death, whichever comes first.

Also known as: cholecalciferol

vitamin D3

Placebo DRUG

Patients will be given placebo within 24 hours of severe sepsis onset followed by weekly doses of placebo until 90 days or death, whichever comes first.

Also known as: sugar pill, sham comparator

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 to \<80 years
• Admitted to 1 of 4 participating ICUs
• Meet criteria for new-onset severe sepsis\* within past 12 hours

You may not qualify if:

• Age ≥80 years
• Not anticipated to survive ≥48 hours
• Inability to obtain informed consent from patient/suitable proxy within 22 hours of new-onset severe sepsis
• Comfort measures, hospice, or palliative care status
• Documented adverse reaction to vitamin D supplementation
• Inability to tolerate enteral feeds/medications
• Renal stones within past year
• Hypercalcemia within past year
• Baseline serum calcium ≥10.5 mg/dL
• Established diagnosis of medical condition associated with high risk of hypercalcemia (e.g. metastatic cancer, sarcoidosis, multiple myeloma, primary hyperparathyroidism)

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Sepsis; Multiple Organ Failure; Critical Illness

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Sadeq A Quraishi, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2016
• First Posted: February 18, 2016
• Study Start: December 1, 2017
• Primary Completion: July 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 5, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)