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CompletedNCT02962102ACTIVATE-AKIUpdated Sep 29, 2025Results posted

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

A Phase 2 interventional study of Calcifediol and Calcitriol in Critically Ill and Acute Kidney Injury, sponsored by David Leaf. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-09-29.

Sponsored by David Leaf · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
150
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Critically Ill
  • Acute Kidney Injury
03

In context

Critical Illness

1,881 studies on the registry are indexed under Critical Illness; 462 are open to participants now.

This study's enrollment of 150 is above the median of 90 across 979 interventional studies indexed under Critical Illness.

Browse Critical Illness studies →

Lead sponsor

This is the only study on the registry with David Leaf as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
150 participants (actual)

Study arms

  • Experimental
    Calcifediol

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

    Drug: Calcifediol

  • Experimental
    Calcitriol

    Calcitriol 4mcg orally daily x 5 days

    Drug: Calcitriol

  • Placebo comparator
    Placebo

    Equal volume of medium chain triglyceride (MCT) oil orally daily x 5 days

    Drug: Placebos

Interventions

  • DrugCalcifediol

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

  • DrugCalcitriol

    Calcitriol 4mcg orally daily x 5

  • DrugPlacebos

    Placebo (medium chain triglyceride oil) orally daily x 5

06

What researchers measure

Primary outcomes

  1. Death Within 7 Days

    All-cause mortality within 7 days following randomization

    Time frame: 7 days

  2. 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

  3. 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

  1. 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

  2. Peak Serum Creatinine (mg/dl)

    Highest serum creatinine value on days 1 to 7

    Time frame: 7 days

  3. 28-day Mortality

    All-cause mortality assessed during the 28 days following randomization

    Time frame: 28 days

  4. 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

Other outcomes

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

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

    Time frame: 7 days

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

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

    Time frame: 7 days

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

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

    Time frame: 7 days

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

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

    Time frame: 7 days

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

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

    Time frame: 7 days

07

Results

Posted Feb 3, 2022
Limitations and caveats
Limited sample size and AKI event rate

Participant flow

Participant flow — Overall Study
MilestoneCalcifediolCalcitriolPlacebo
Started515049
Completed515049
Not completed000

Outcome measures

PrimaryDeath Within 7 Days

All-cause mortality within 7 days following randomization

Time frame:
7 days
Reported as:
Count of participants · Participants
Death Within 7 Days
ParticipantsCalcifediolCalcitriolPlacebo
Death Within 7 Days496
Statistical analysis
  • Calcifediol vs Placebo · Fisher Exact · p = 0.52
  • Calcitriol vs Placebo · Fisher Exact · p = 0.58
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants Who Received Renal Replacement Therapy Within 7 Days
ParticipantsCalcifediolCalcitriolPlacebo
Number of Participants Who Received Renal Replacement Therapy Within 7 Days114
Statistical analysis
  • Calcifediol vs Placebo · Fisher Exact · p = 0.20
  • Calcitriol vs Placebo · Fisher Exact · p = 0.20
PrimaryRelative 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
Reported as:
Median · Relative average percent increase
Relative Average Change in Serum Creatinine From Day 0 to Days 1-7
Relative average percent increaseCalcifediolCalcitriolPlacebo
Relative Average Change in Serum Creatinine From Day 0 to Days 1-7-2.3 (-20.7 to 18.3)-7.1 (-18.1 to 12.3)-7.4 (-21.5 to 10.4)
Statistical analysis
  • Calcifediol vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.44
  • Calcitriol vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.29
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants With New or Worsening Stage of AKI, Defined by KDIGO Guidelines
ParticipantsCalcifediolCalcitriolPlacebo
Number of Participants With New or Worsening Stage of AKI, Defined by KDIGO Guidelines202319
SecondaryPeak Serum Creatinine (mg/dl)

Highest serum creatinine value on days 1 to 7

Time frame:
7 days
Reported as:
Median · mg/dl
Peak Serum Creatinine (mg/dl)
mg/dlCalcifediolCalcitriolPlacebo
Peak Serum Creatinine (mg/dl)1.2 (0.8 to 1.5)1.3 (0.8 to 1.9)1.2 (0.9 to 1.8)
Secondary28-day Mortality

All-cause mortality assessed during the 28 days following randomization

Time frame:
28 days
Reported as:
Count of participants · Participants
28-day Mortality
ParticipantsCalcifediolCalcitriolPlacebo
28-day Mortality101610
SecondaryICU- 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
Reported as:
Median · Days
ICU- and Hospital-free Days
DaysCalcifediolCalcitriolPlacebo
ICU-free days20 (2 to 25)16 (0 to 25)11 (0 to 22)
Hospital-free days5 (0 to 17)4 (0 to 15)0 (0 to 15)
Other pre-specifiedKidney Injury - Subgroup Analysis Based on Time Zero 25-hydroxyvitamin D Level Above Versus Below the Median

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

Time frame:
7 days

Results for this outcome have not been posted.

Other pre-specifiedKidney Injury - Subgroup Analysis Based on the Presence or Absence of AKI on Enrollment

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

Time frame:
7 days

Results for this outcome have not been posted.

Other pre-specifiedKidney Injury - Subgroup Analysis Based on APACHE II Score on Enrollment Above Versus Below the Median

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

Time frame:
7 days

Results for this outcome have not been posted.

Other pre-specifiedKidney Injury - Subgroup Analysis Based on ICU Type (Medical Versus Surgical)

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

Time frame:
7 days

Results for this outcome have not been posted.

Other pre-specifiedKidney Injury - Subgroup Analysis Based on the Presence or Absence of Sepsis on Enrollment

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

Time frame:
7 days

Results for this outcome have not been posted.

Adverse events

Collected over 7 days for hypercalcemia and 28 days for all-cause mortality. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Calcifediol10/51 (19.6%)0/51 (0%)1/51 (2%)
Calcitriol16/50 (32%)0/50 (0%)1/50 (2%)
Placebo10/49 (20.4%)0/49 (0%)0/49 (0%)
Most frequent other events
Most frequent other events
EventCalcifediolCalcitriolPlacebo
HypercalcemiaEndocrine disorders1/511/500/49

Baseline characteristics

Age, Continuous
Age, Continuous(years)CalcifediolCalcitriolPlaceboTotal
Median64 (53 to 72)65 (53 to 74)65 (51 to 71)65 (52 to 72)
Sex: Female, Male
Sex: Female, Male(Participants)CalcifediolCalcitriolPlaceboTotal
Female19211858
Male32293192
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)CalcifediolCalcitriolPlaceboTotal
Hispanic or Latino44311
Not Hispanic or Latino454546136
Unknown or Not Reported2103
Race (NIH/OMB)
Race (NIH/OMB)(Participants)CalcifediolCalcitriolPlaceboTotal
American Indian or Alaska Native0000
Asian0145
Native Hawaiian or Other Pacific Islander0000
Black or African American57315
White434041124
More than one race2103
Unknown or Not Reported1113
Baseline estimated glomerular filtration rate (eGFR)
Baseline estimated glomerular filtration rate (eGFR)(ml/min/1.73m^2)CalcifediolCalcitriolPlaceboTotal
Median94 (77 to 118)98 (72 to 121)94 (78 to 109)95 (75 to 117)
APACHE II score
APACHE II score(units on a scale)CalcifediolCalcitriolPlaceboTotal
Median26 (21 to 30)25 (21 to 31)27 (22 to 30)25 (21 to 30)
Invasive mechanical ventilation
Invasive mechanical ventilation(Participants)CalcifediolCalcitriolPlaceboTotal
Count of participants414341125
Vasopressors/inotropes
Vasopressors/inotropes(Participants)CalcifediolCalcitriolPlaceboTotal
Count of participants28283086

2 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Brigham and Women's Hospital
    Boston, Massachusetts 02115, United States
09

References and documents

Publications

  • Leaf DE, Shenoy T, Zinchuk K, Gupta S, Dias JA, Sanchez-Almanzar D, Ginde AA, Athar H, Cheng C, Tamura T, Kim EY, Waikar SS. Randomized trial of activated vitamin D for acute kidney injury prevention in critically ill patients. JCI Insight. 2025 Sep 9;10(20):e193523. doi: 10.1172/jci.insight.193523. eCollection 2025 Oct 22. PubMed 40924491 ↗

Study documents

  • Protocol and statistical analysis plan · Dec 25, 2018
  • Informed consent form · Dec 25, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 29, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02962102
Lead sponsor
David Leaf
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Responsible party
David Leaf (Assistant Professor of Medicine, Harvard Medical School, Brigham and Women's Hospital) — Sponsor-investigator
First posted
Nov 11, 2016
Start date
Apr 3, 2017
Primary completion
Jul 16, 2020
Completion
Aug 6, 2020
Results posted
Feb 3, 2022
Last update
Sep 29, 2025

Study contacts

David E Leaf, MD, MMSc
principal investigator · Brigham and Women's Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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