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| ID | Type | Description | Link |
|---|---|---|---|
| 5K23DK106448 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Calcifediol | Experimental | Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4 |
|
| Calcitriol | Experimental | Calcitriol 4mcg orally daily x 5 days |
|
| Placebo | Placebo Comparator | Equal volume of medium chain triglyceride (MCT) oil orally daily x 5 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Calcifediol | Drug | Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Death Within 7 Days | All-cause mortality within 7 days following randomization | 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 | 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 | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 7 days |
| Kidney Injury - Subgroup Analysis Based on the Presence or Absence of AKI on Enrollment |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David E Leaf, MD, MMSc | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40924491 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Calcifediol | Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4 Calcifediol: Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4 |
| FG001 | Calcitriol | Calcitriol 4mcg orally daily x 5 days Calcitriol: Calcitriol 4mcg orally daily x 5 |
| FG002 | Placebo | Equal volume of medium chain triglyceride (MCT) oil orally daily x 5 days Placebos: Placebo (medium chain triglyceride oil) orally daily x 5 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Calcifediol | Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4 Calcifediol: Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4 |
| BG001 | Calcitriol |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Death Within 7 Days | All-cause mortality within 7 days following randomization | Posted | Count of Participants | Participants | 7 days |
|
7 days for hypercalcemia and 28 days for all-cause mortality
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Calcifediol | Calcifediol 400mcg PO/NGT/OGT x 1, followed by 200mcg PO/NGT/OGT daily x 4 Calcifediol: Calcifediol 400mcg PO/NGT/OGT x 1, followed by 200mcg PO/NGT/OGT daily x 4 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypercalcemia | Endocrine disorders | Systematic Assessment | Serum calcium >10.7 mg/dl within 7 days following randomization |
Limited sample size and AKI event rate
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. David Leaf | Brigham and Women's Hospital | 617-525-7612 | deleaf@bwh.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 25, 2018 | Dec 7, 2021 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 25, 2018 | Dec 7, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D016638 | Critical Illness |
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D051437 | Renal Insufficiency |
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| ID | Term |
|---|---|
| D002112 | Calcifediol |
| D002117 | Calcitriol |
| ID | Term |
|---|---|
| D006887 | Hydroxycholecalciferols |
| D002762 | Cholecalciferol |
| D002782 | Cholestenes |
| D002776 | Cholestanes |
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| Calcitriol |
| Drug |
Calcitriol 4mcg orally daily x 5 |
|
| Placebos | Drug | Placebo (medium chain triglyceride oil) orally daily x 5 |
|
| 7 days |
| Peak Serum Creatinine (mg/dl) | Highest serum creatinine value on days 1 to 7 | 7 days |
| 28-day Mortality | All-cause mortality assessed during the 28 days following randomization | 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 | 28 days |
Composite of daily serum creatinine, need for renal replacement therapy (RRT), or death within 7 days |
| 7 days |
| 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 | 7 days |
| 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 | 7 days |
| 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 | 7 days |
Calcitriol 4mcg orally daily x 5 days
Calcitriol: Calcitriol 4mcg orally daily x 5
| BG002 | Placebo | Equal volume of medium chain triglyceride (MCT) oil orally daily x 5 days Placebos: Placebo (medium chain triglyceride oil) orally daily x 5 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Baseline estimated glomerular filtration rate (eGFR) | Calculated based on the Chronic Kidney Disease-Epidemiology Collaboration equation | Median | Inter-Quartile Range | ml/min/1.73m^2 |
|
| APACHE II score | Acute Physiology and Chronic Health Evaluation II (APACHE II), an intensive care unit severity of illness scoring system ranging from 0 to 71, with higher scores indicating more severe disease | Median | Inter-Quartile Range | units on a scale |
|
| Invasive mechanical ventilation | Count of Participants | Participants |
|
| Vasopressors/inotropes | Count of Participants | Participants |
|
| Acute kidney injury | Defined as an increase in serum creatinine ≥0.3 mg/d within the previous 48 hours, ≥50% within the previous 7 days, or urine output ≤0.5 ml/kg/h for 6 consecutive hours | Count of Participants | Participants |
|
| Plasma 25-hydroxyvitamin D | Median | Inter-Quartile Range | ng/ml |
|
Equal volume of medium chain triglyceride (MCT) oil daily x 5 days
Placebos: Placebo (medium chain triglyceride oil) daily x 5
|
|
|
| Primary | Number of Participants Who Received Renal Replacement Therapy Within 7 Days | Number of participants who received renal replacement therapy within 7 days following randomization | Posted | Count of Participants | Participants | 7 days |
|
|
|
|
| Primary | 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 | Posted | Median | Inter-Quartile Range | Relative average percent increase | 7 days |
|
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Secondary | Peak Serum Creatinine (mg/dl) | Highest serum creatinine value on days 1 to 7 | Posted | Median | Inter-Quartile Range | mg/dl | 7 days |
|
|
|
| Secondary | 28-day Mortality | All-cause mortality assessed during the 28 days following randomization | Posted | Count of Participants | Participants | 28 days |
|
|
|
| Secondary | 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 | Posted | Median | Inter-Quartile Range | Days | 28 days |
|
|
|
| Other Pre-specified | 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 | Not Posted | 7 days | Participants |
| Other Pre-specified | 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 | Not Posted | 7 days | Participants |
| Other Pre-specified | 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 | Not Posted | 7 days | Participants |
| Other Pre-specified | 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 | Not Posted | 7 days | Participants |
| Other Pre-specified | 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 | Not Posted | 7 days | Participants |
| 10 |
| 51 |
| 0 |
| 51 |
| 1 |
| 51 |
| EG001 | Calcitriol | Calcitriol 4mcg PO/NGT/OGT daily x 5 days Calcitriol: Calcitriol 4mcg PO/NGT/OGT daily x 5 | 16 | 50 | 0 | 50 | 1 | 50 |
| EG002 | Placebo | Equal volume of medium chain triglyceride (MCT) oil daily x 5 days Placebos: Placebo (medium chain triglyceride oil) daily x 5 | 10 | 49 | 0 | 49 | 0 | 49 |
|
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| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
| D004100 | Dihydroxycholecalciferols |
| Superiority |
| Superiority |
|