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

David Leaf

Status and phase: Completed; Phase 2

Conditions: Critically Ill; Acute Kidney Injury

Treatments: Drug: Calcitriol; Drug: Placebos; Drug: Calcifediol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02962102

2016P002527

5K23DK106448 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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150 participants in 3 patient groups, including a placebo group

Calcifediol

Experimental group

Description:

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

Treatment:

Drug: Calcifediol

Calcitriol

Experimental group

Description:

Calcitriol 4mcg orally daily x 5 days

Treatment:

Drug: Calcitriol

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebos