Critically IllPhase 2ACTIVATE-AKINCT02962102

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

A Phase 2 study testing Calcifediol and Calcitriol in people with Critically Ill and Acute Kidney Injury, run by David Leaf at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Critically Ill, Acute Kidney Injury
What is being tested?: Calcifediol and Calcitriol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 150 participants
Where: 1 siteUnited States
Study dates: 3 Apr 2017to 6 Aug 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 13Show fewer

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 locations and contacts

1 site in 1 country.

United States1 site

Brigham and Women's Hospital
Boston, Massachusetts, 02115

Other trials in United States

About this study

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

Read the 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.

Conditions: Critically Ill, Acute Kidney Injury
Being tested: Calcifediol, Calcitriol, Placebos
Medical subject headings: Critical Illness, Acute Kidney Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CalcifediolDrug
Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4
CalcitriolDrug
Calcitriol 4mcg orally daily x 5
PlacebosDrug
Placebo (medium chain triglyceride oil) orally daily x 5

Study groups in NCT02962102
Study group	Role	What they receive
Calcifediol	Experimental	Calcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4 Receives: Drug: Calcifediol
Calcitriol	Experimental	Calcitriol 4mcg orally daily x 5 days Receives: Drug: Calcitriol
Placebo	Placebo comparator	Equal volume of medium chain triglyceride (MCT) oil orally daily x 5 days Receives: Drug: Placebos

What is being measured

The primary outcome is the main question the study is designed to answer.

Death Within 7 Days
All-cause mortality within 7 days following randomization
Measured: 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
Measured: 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
Measured: 7 days

Secondary outcomes (4)

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.
Measured: 7 days
Peak Serum Creatinine (mg/dl)
Highest serum creatinine value on days 1 to 7
Measured: 7 days
28-day Mortality
All-cause mortality assessed during the 28 days following randomization
Measured: 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
Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Apr 20176 Aug 2020

First posted11 Nov 2016 (estimated)
Study start3 Apr 2017
Primary completion16 Jul 2020
Study completion6 Aug 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Critically IllStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 150 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02962102
Sponsor's protocol ID: 2016P002527
Other IDs: 5K23DK106448
Acronym: ACTIVATE-AKI
Status last verified: Sep 2025
First submitted: 3 Nov 2016
Last updated: 29 Sep 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 40924491

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 29 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Activated Vitamin D for the Prevention and Treatment of Acute Kidney Injury (ACTIVATE-AKI)
ClinicalTrials.gov ID: NCT02962102
Acronym / sponsor ID: ACTIVATE-AKI / 2016P002527
Conditions: Critically Ill, Acute Kidney Injury
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 150 participants (actual)
Lead sponsor: David LeafUniversity, hospital or other
Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study start: 3 Apr 2017 (actual)
Primary completion: 16 Jul 2020 (actual)
Study completion: 6 Aug 2020 (actual)
First posted: 11 Nov 2016 (estimated)
Results: Posted 3 Feb 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Calcifediol	Experimental	Drug: CalcifediolCalcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4
Calcitriol	Experimental	Drug: CalcitriolCalcitriol 4mcg orally daily x 5 days
Placebo	Placebo comparator	Drug: PlacebosEqual volume of medium chain triglyceride (MCT) oil orally daily x 5 days

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (13 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CalcifediolCalcifediol 400mcg orally x 1, followed by 200mcg orally daily x 4	Drug	Calcifediol
CalcitriolCalcitriol 4mcg orally daily x 5	Drug	Calcitriol
PlacebosPlacebo (medium chain triglyceride oil) orally daily x 5	Drug	Placebo

Primary outcome

Death Within 7 Days
Time frame: 7 days
All-cause mortality within 7 days following randomization
Number of Participants Who Received Renal Replacement Therapy Within 7 Days
Time frame: 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
Time frame: 7 days
Average percentage change in serum creatinine assessed on days 1-7 as compared to day 0

4 secondary outcomes

Number of Participants With New or Worsening Stage of AKI, Defined by KDIGO Guidelines
Time frame: 7 days
Peak Serum Creatinine (mg/dl)
Time frame: 7 days
28-day Mortality
Time frame: 28 days
ICU- and Hospital-free Days
Time frame: 28 days

Results and safety

Results posted to the registry on 3 Feb 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Calcifediol	51	51
Calcitriol	50	50
Placebo	49	49

Primary outcome: Death Within 7 Days

Time frame: 7 days. Count of participants. Unit: Participants

Measure	Calcifediol n = 51	Calcitriol n = 50	Placebo n = 49
Value	4	9	6

Calcifediol vs Placebo: p = 0.52, Fisher Exact
Calcitriol vs Placebo: p = 0.58, Fisher Exact

Primary outcome: Number of Participants Who Received Renal Replacement Therapy Within 7 Days

Time frame: 7 days. Count of participants. Unit: Participants

Measure	Calcifediol n = 51	Calcitriol n = 50	Placebo n = 49
Value	1	1	4

Calcifediol vs Placebo: p = 0.20, Fisher Exact
Calcitriol vs Placebo: p = 0.20, Fisher Exact

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

Time frame: 7 days. Median (Inter-Quartile Range). Unit: Relative average percent increase

Measure	Calcifediol n = 51	Calcitriol n = 50	Placebo n = 49
Value	-2.3 (-20.7 to 18.3)	-7.1 (-18.1 to 12.3)	-7.4 (-21.5 to 10.4)

Calcifediol vs Placebo: p = 0.44, Wilcoxon (Mann-Whitney)
Calcitriol vs Placebo: p = 0.29, Wilcoxon (Mann-Whitney)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 7 days for hypercalcemia and 28 days for all-cause mortality. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Calcifediol	0 of 51 (0%)	1 of 51 (2%)	10 of 51
Calcitriol	0 of 50 (0%)	1 of 50 (2%)	16 of 50
Placebo	0 of 49 (0%)	0 of 49 (0%)	10 of 49

Limitations and caveats (from the sponsor): Limited sample size and AKI event rate

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 40924491Leaf 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David E Leaf, MD, MMSc principal investigator

Brigham and Women's Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Calcifediol and Calcitriol in people with Critically Ill and Acute Kidney Injury, run by David Leaf at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Death Within 7 Days (time frame: 7 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02962102, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2025.