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

NCT02962102 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2016P0025275K23DK106448
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Critically Ill; Acute Kidney Injury

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (4)

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

  7 days

• Peak Serum Creatinine (mg/dl)

  7 days

• 28-day Mortality

  28 days

• ICU- and Hospital-free Days

  28 days

Other Outcomes (5)

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

  7 days

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

  7 days

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

  7 days

Study Arms (3)

Calcifediol

EXPERIMENTAL

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

Drug: Calcifediol

Calcitriol

EXPERIMENTAL

Calcitriol 4mcg orally daily x 5 days

Drug: Calcitriol

Placebo

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Calcifediol DRUG

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

Calcifediol

Calcitriol DRUG

Calcitriol 4mcg orally daily x 5

Calcitriol

Placebos DRUG

Placebo (medium chain triglyceride oil) orally daily x 5

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• David Leaf: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 40924491 RESULT

MeSH Terms

Conditions

Critical Illness; Acute Kidney Injury

Interventions

Calcifediol; Calcitriol

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Dihydroxycholecalciferols

Limitations and Caveats

Limited sample size and AKI event rate

Results Point of Contact

• Title: Dr. David Leaf
• Organization: Brigham and Women's Hospital

deleaf@bwh.harvard.edu

617-525-7612

Study Officials

• David E Leaf, MD, MMSc

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine, Harvard Medical School

Study Record Dates

• First Submitted: November 3, 2016
• First Posted: November 11, 2016
• Study Start: April 3, 2017
• Primary Completion: July 16, 2020
• Study Completion: August 6, 2020
• Last Updated: September 29, 2025
• Results First Posted: February 3, 2022

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)