Cholecalciferol (colecalciferol) for Sepsis|Pneumonia

Inclusion criteria

• {"criterion_text":"- Age ≥ 65 years (no gender restriction);"}
• {"criterion_text":"- Fulfillment of one of the two following diagnostic criteria: •\tDiagnosis of pneumonia due to a presumed infection, confirmed by chest plain radiographs or CT scan, according to the ATS/IDSA guidelines [Metlay et al., 2019; Mandell et al., 2007] (including COVID-19 related pneumonia confirmed by a RT-PCR or third-generation antigenic test) (pneumonia section of the study); •\tDiagnosis of sepsis (patients meeting the Third International Consensus Definitions for Sepsis; Sepsis-3 [Singer et al., 2016]) (sepsis section of the study);"}
• {"criterion_text":"- Need for hospitalization in a non-intensive care unit (non-ICU) (hospitalization in general wards including high dependency/sub-intensive wards);"}
• {"criterion_text":"- Serum 25(OH)D < 20 ng/ml at admission."}
• {"criterion_text":"- Symptoms onset from no more than 10 days;"}
• {"criterion_text":"- NEWS2>2;"}
• {"criterion_text":"- Patient or his/her legal representative ability to understand, sign, and date the written authorized informed consent form."}

Exclusion criteria

• {"criterion_text":"- Extremely critical presentation, suggestive of immediate need for ICU admission of imminent death;"}
• {"criterion_text":"- Sepsis renal failure (GFR < 15 ml/min) or history of recurrent nephrolithiasis;"}
• {"criterion_text":"- Hypercalcemia (ionized serum calcium > 1.4 mmol/l (5.6 mg/dl) or albumin-adjusted serum calcium > 2.63 mmol/l (10.5 mg/dl));"}
• {"criterion_text":"- History of chronic liver diseases associated to liver failure (i.e. hepatic cirrhosis CHILDB or greater);"}
• {"criterion_text":"- Known malabsorption syndromes;"}
• {"criterion_text":"- Participation in a clinical trial in which an investigational drug was administered within 30 days of screening or within 5 half-lives of the study drug, whichever is longer."}
• {"criterion_text":"- Known sarcoidosis;"}
• {"criterion_text":"- Known primary hyperparathyroidism;"}
• {"criterion_text":"- History of nephrocalcinosis;"}
• {"criterion_text":"- History of hypercalciuria (urinary calcium excretion > 0.1 mmol/kg body weight/day (4 mg/kg body weight/day));"}
• {"criterion_text":"- BMI > 35 kg/m2;"}
• {"criterion_text":"- Inability to tolerate or clinical conditions contraindicating oral therapy or vitamin D supplementation."}
• {"criterion_text":"- Advanced cancer or other advanced chronic diseases with an estimated prognosis of less than 30 days;"}
• {"criterion_text":"- Known history of allergy/intolerance to cholecalciferol (vitamin D3) or any excipient used in the intervention formulation;"}

Primary endpoints

• {"endpoint_text":"- 1) Evaluation of a high dose vitamin D3 regimen effectiveness with respect to placebo in modifying one of the following (whichever occurs first): •\tDifference in the proportion of patients reaching an in-hospital negative outcome (in-hospital death or ICU admission), within 10 days from admission; •\tDifference in the proportion of patients reaching an in-hospital positive outcome (discharge or clinical resolution of symptoms (stable NEWS2<2 for at least 24 hours) within 10 days from admission)","definition_or_measurement_approach":"Difference in proportions between treatment and placebo groups of patients reaching either an in-hospital negative outcome (in-hospital death or ICU admission) within 10 days from admission OR an in-hospital positive outcome (discharge or clinical resolution defined as stable NEWS2<2 for at least 24 hours) within 10 days from admission; measured as proportion achieving outcome within 10 days and compared between arms."}
• {"endpoint_text":"- 2) Evaluation of a high dose vitamin D3 regimen effectiveness with respect to placebo in modifying one of the following: •\tDifference in the proportion of patient with a 50% reduction of circulating Il-6 within 10 days from admission; •\tDifference in the proportion of patient with a 50% reduction of circulating C-reactive protein (CRP) within 10 days from admission;","definition_or_measurement_approach":"Difference in proportions between treatment and placebo groups of patients achieving a ≥50% reduction in circulating IL-6 within 10 days from admission, or a ≥50% reduction in CRP within 10 days from admission; measured by serial biomarker assays up to 10 days."}

Secondary endpoints

• {"endpoint_text":"- Difference in the proportion of patients reaching an in-hospital negative or positive outcome (as previously defined) among patient stratified by age (65-80 years old and ≥80 years old);","definition_or_measurement_approach":"Same in-hospital negative/positive outcomes as primary endpoint, analyzed by age strata 65-80 and ≥80."}
• {"endpoint_text":"- Difference in oxygen supplementation and/or mechanical non-invasive ventilation need and its duration (only for patients of the pneumonia section of the study);","definition_or_measurement_approach":"Proportion requiring oxygen supplementation or non-invasive mechanical ventilation and duration (days) compared between arms for pneumonia cohort."}
• {"endpoint_text":"- Difference in mortality rate at 10, 14, 28 and 90 days;","definition_or_measurement_approach":"All-cause mortality rates at specified time points (10, 14, 28, 90 days) compared between treatment and placebo groups."}
• {"endpoint_text":"- Difference in hospitalization length (expressed in days);","definition_or_measurement_approach":"Length of hospital stay in days compared between arms."}
• {"endpoint_text":"- Difference in plasma vitamin D levels at 2-5-7-10 days (vitamin D quantification data will be extracted from both study-specific blood draws (at 7 and 10 days) and from blood draws performed in order to monitor intervention safety (at 2 and 5 days));","definition_or_measurement_approach":"Serial plasma 25(OH)D measurements at days 2, 5, 7, 10 compared between arms."}
• {"endpoint_text":"- Difference in the proportion of CRP levels reduction below 1 mg/ml at 7 and 10 days;","definition_or_measurement_approach":"Proportion of patients with CRP <1 mg/ml at days 7 and 10 compared between arms."}
• {"endpoint_text":"- Difference in inflammatory biomarkers panel (see protocol) at 2-5-7-10 days;","definition_or_measurement_approach":"Changes in specified inflammatory biomarker panel measured at days 2,5,7,10 compared between groups."}
• {"endpoint_text":"- Difference in the proportion of patients reaching an in-hospital negative or positive outcome (as previously defined) among patient stratified by Vitamin D plasma levels at 10 days from admisison (<20 ng/ml and ≥20 ng/ml);","definition_or_measurement_approach":"Analysis of primary in-hospital outcomes stratified by plasma 25(OH)D at day 10 (<20 ng/ml vs ≥20 ng/ml)."}
• {"endpoint_text":"- Difference in adverse events and proportion of severe adverse events","definition_or_measurement_approach":"Comparison of adverse event rates and severe adverse event proportions between treatment and placebo arms (safety monitoring)."}

Italy

Earliest CTIS Part Ii Submission Date

06-08-2025

Latest Decision Or Authorization Date

10-09-2025

Processing Time Days

35

Number Of Sites

2

Number Of Participants

552

Primary sponsor

Full Name

Azienda Ospedaliero-Universitaria Maggiore Della Carita

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"MUR, PRIN2022 call (project identifier: 2022BPNY3E)","duties_or_roles":"","organisation_type":""}
• {"country":"Italy","full_name":"Abiogen Pharma S.p.A (investigational product and placebo)","duties_or_roles":"Provision of investigational product and placebo","organisation_type":""}