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

Acute Kidney Injury Clinical Trial

— ACTIVATE-AKI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02962102
• Other study ID #: 2016P002527
• Secondary ID: 5K23DK106448
• Status: Completed
• Phase: Phase 2
• Start date: April 3, 2017
• Est. completion date: August 6, 2020

Study information

• Verified date: January 2022
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: August 6, 2020
• Est. primary completion date: July 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Critical Illness
• Critically Ill
• Wounds and Injuries

Intervention

Drug:
• Calcifediol
Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4
• Calcitriol
Calcitriol 4mcg orally daily x 5
• Placebos
Placebo (medium chain triglyceride oil) orally daily x 5

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
David Leaf	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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	7 days
Other	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
Other	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
Other	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
Primary	Death Within 7 Days	All-cause mortality within 7 days following randomization	7 days
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	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	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.	7 days
Secondary	Peak Serum Creatinine (mg/dl)	Highest serum creatinine value on days 1 to 7	7 days
Secondary	28-day Mortality	All-cause mortality assessed during the 28 days following randomization	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	28 days