Clinical trial NCT02962102: Activated Vitamin D for the Prevention and Treatment of Acute Kidney Injury
Official title: Activated Vitamin D for the Prevention and Treatment of Acute Kidney Injury (ACTIVATE-AKI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Critically Ill
Acute Kidney Injury
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2016-11-11
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Death Within 7 Days
timeFrame: 7 days
measure: Number of Participants Who Received Renal Replacement Therapy Within 7 Days
timeFrame: 7 days
measure: Relative Average Change in Serum Creatinine From Day 0 to Days 1-7
timeFrame: 7 days
Secondary outcomes:
measure: Number of Participants With New or Worsening Stage of AKI, Defined by KDIGO Guidelines
timeFrame: 7 days
measure: Peak Serum Creatinine (mg/dl)
timeFrame: 7 days
measure: 28-day Mortality
timeFrame: 28 days
measure: ICU- and Hospital-free Days
timeFrame: 28 days
Other outcomes:
measure: Kidney Injury - Subgroup Analysis Based on Time Zero 25-hydroxyvitamin D Level Above Versus Below the Median
timeFrame: 7 days
measure: Kidney Injury - Subgroup Analysis Based on the Presence or Absence of AKI on Enrollment
timeFrame: 7 days
measure: Kidney Injury - Subgroup Analysis Based on APACHE II Score on Enrollment Above Versus Below the Median
timeFrame: 7 days
measure: Kidney Injury - Subgroup Analysis Based on ICU Type (Medical Versus Surgical)
timeFrame: 7 days
measure: Kidney Injury - Subgroup Analysis Based on the Presence or Absence of Sepsis on Enrollment
timeFrame: 7 days
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: David E Leaf, MD, MMSc
role: PRINCIPAL_INVESTIGATOR
References: