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

Primary Purpose

Critically Ill, Acute Kidney Injury

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Calcifediol

Calcitriol

Placebos

About this trial

This is an interventional prevention trial for Critically Ill

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Calcifediol

Calcitriol

Placebo

Arm Description

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

Calcitriol 4mcg orally daily x 5 days

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

Outcomes

Primary Outcome Measures

Death Within 7 Days

All-cause mortality within 7 days following randomization

Number of Participants Who Received Renal Replacement Therapy Within 7 Days

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

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

Secondary Outcome Measures

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.

Peak Serum Creatinine (mg/dl)

Highest serum creatinine value on days 1 to 7

28-day Mortality

All-cause mortality assessed during the 28 days following randomization

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

Full Information

NCT ID

NCT02962102

First Posted

November 3, 2016

Last Updated

January 5, 2022

Sponsor

David Leaf

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT02962102

Brief Title

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

Acronym

ACTIVATE-AKI

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Completed

Study Start Date

April 3, 2017 (Actual)

Primary Completion Date

July 16, 2020 (Actual)

Study Completion Date

August 6, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

David Leaf

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Critically Ill, Acute Kidney Injury

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

150 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Calcifediol

Arm Type

Experimental

Arm Description

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

Arm Title

Calcitriol

Arm Type

Experimental

Arm Description

Calcitriol 4mcg orally daily x 5 days

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Calcifediol

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Calcitriol

Intervention Description

Calcitriol 4mcg orally daily x 5

Intervention Type

Drug

Intervention Name(s)

Placebos

Intervention Description

Placebo (medium chain triglyceride oil) orally daily x 5

Primary Outcome Measure Information:

Title

Death Within 7 Days

Description

All-cause mortality within 7 days following randomization

Time Frame

7 days

Title

Number of Participants Who Received Renal Replacement Therapy Within 7 Days

Description

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

Time Frame

7 days

Title

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

Description

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

Time Frame

7 days

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

7 days

Title

Peak Serum Creatinine (mg/dl)

Description

Highest serum creatinine value on days 1 to 7

Time Frame

7 days

Title

28-day Mortality

Description

All-cause mortality assessed during the 28 days following randomization

Time Frame

28 days

Title

ICU- and Hospital-free Days

Description

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 Pre-specified Outcome Measures:

Title

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

Description