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Completed

NCT Number: NCT02962102

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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Calcifediol

Drug

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

calcitriol

Drug

Calcitriol 4mcg orally daily x 5

Placebos

Drug

Placebo (medium chain triglyceride oil) orally daily x 5

Primary outcomes

  1. Death Within 7 Days

    Time frame: 7 days

    All-cause mortality within 7 days following randomization

  2. Number of Participants Who Received Renal Replacement Therapy Within 7 Days

    Time frame: 7 days

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

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

    Time frame: 7 days

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

Secondary outcomes

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

    Time frame: 7 days

    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.

  2. Peak Serum Creatinine (mg/dl)

    Time frame: 7 days

    Highest serum creatinine value on days 1 to 7

  3. 28-day Mortality

    Time frame: 28 days

    All-cause mortality assessed during the 28 days following randomization

  4. ICU- and Hospital-free Days

    Time frame: 28 days

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

Other outcomes

  1. Kidney Injury - Subgroup Analysis Based on Time Zero 25-hydroxyvitamin D Level Above Versus Below the Median

    Time frame: 7 days

    Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days

  2. Kidney Injury - Subgroup Analysis Based on the Presence or Absence of AKI on Enrollment

    Time frame: 7 days

    Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days

  3. Kidney Injury - Subgroup Analysis Based on APACHE II Score on Enrollment Above Versus Below the Median

    Time frame: 7 days

    Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days

  4. Kidney Injury - Subgroup Analysis Based on ICU Type (Medical Versus Surgical)

    Time frame: 7 days

    Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days

  5. Kidney Injury - Subgroup Analysis Based on the Presence or Absence of Sepsis on Enrollment

    Time frame: 7 days

    Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days

Sponsors and collaborators

Lead sponsor

David Leaf

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Official study title

Activated Vitamin D for the Prevention and Treatment of Acute Kidney Injury (ACTIVATE-AKI)

Acronym: ACTIVATE-AKI

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Nov 11, 2016
Registry last updated
Sep 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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