Activated Vitamin D for the Prevention and Treatment of Acute Kidney Injury

David Leaf150 enrolled

Overview

The purpose of this study is to assess the efficacy of calcifediol (25-hydroxyvitamin D) and calcitriol (1,25-dihydroxyvitamin D) in preventing and reducing the severity of acute kidney injury (AKI) in critically ill patients.

Decreased circulating levels of active vitamin D metabolites, including 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are common in critically ill patients, and lower levels are independently associated with a higher risk of acute kidney injury (AKI). Further, administration of 25D and 1,25D attenuates AKI in animal models. The purpose of this study is to assess if administration of 25D and 1,25D decreases the incidence and severity of AKI in critically ill patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

150

Conditions

Critically Ill Acute Kidney Injury

Interventions

CalcifediolDRUG

Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4

CalcitriolDRUG

Calcitriol 4mcg orally daily x 5

PlacebosDRUG

Placebo (medium chain triglyceride oil) orally daily x 5

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 * Admitted to the ICU within 48h prior to enrollment * Likely to remain in the ICU (alive) for ≥72h * Naso/orogastric tube or ability to swallow * High risk of severe AKI Exclusion Criteria: * Serum total calcium \> 9.0 mg/dl or phosphate \> 6.0 mg/dL within previous 48h * Currently receiving oral calcium supplementation * Ingestion of vitamin D3 \>1,000 IU/day or any 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D during the previous 7 days * AKI stage 2 or 3 (based on KDIGO serum creatinine and/or urine output criteria) * History of transplantation or receiving chronic (\>7days) of immunosuppressive medications (not including glucocorticoid steroids at a dose less than or equivalent to prednisone 20 mg/day) * Neutropenia in the previous 48h * Active primary parathyroid disease, active granulomatous disease, or symptomatic nephrolithiasis in the previous 3 months * Receiving cytochrome P450 inhibitors * Chronic Kidney Disease stage V or End Stage Renal Disease * Hemoglobin \< 7 g/dL * GI malabsorption * Prisoner * Pregnancy or breast feeding

Locations (1)

Brigham and Women's Hospital

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

Death Within 7 Days

All-cause mortality within 7 days following randomization

Time frame: 7 days

Number of Participants Who Received Renal Replacement Therapy Within 7 Days

Number of participants who received renal replacement therapy within 7 days following randomization

Time frame: 7 days

Relative Average Change in Serum Creatinine From Day 0 to Days 1-7

Average percentage change in serum creatinine assessed on days 1-7 as compared to day 0

Time frame: 7 days

Secondary Outcomes

Number of Participants With New or Worsening Stage of AKI, Defined by KDIGO Guidelines

Any of the following: 1) an increase in serum creatinine ≥50% compared to the immediate pre-randomization value; 2) new or progressive stage of oliguria; or 3) receipt of renal replacement therapy. Oliguria stages 1, 2, and 3 are defined as urine output (UOP) \<0.5 ml/kg/h for 6-12h, \<0.5 ml/kg/h for \>12h, and \<0.3 ml/kg/h for ≥24h or anuria for ≥12h, respectively.

Time frame: 7 days

Peak Serum Creatinine (mg/dl)

Highest serum creatinine value on days 1 to 7

Time frame: 7 days

28-day Mortality

All-cause mortality assessed during the 28 days following randomization

Time frame: 28 days

ICU- and Hospital-free Days

28 minus the number of days in the ICU or hospital, with 0 assigned to patients who die before 28 days

Time frame: 28 days

Data from ClinicalTrials.gov

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