Biomarker Rule in/Out in Patients With Acute Diseases for Validation of AKI (BRAVA) Acute Kidney Injury (BRAVA)

The Potential Role of Biomarkers (Urine TIMP-IGFBP7) in Determining the Incidence of Acute Kidney Injury (AKI) in All-comers Patients Presenting to the Emergency Department With Acute Diseases

The presence or development of AKI impacts on outcomes in patients presenting with acute conditions to the ED. As a result, treating physicians are often concerned with the risk of AKI and take such risk in consideration when making subsequent therapeutic and diagnostic decisions which may result in delaying or withholding therapeutic measures in order to prevent further kidney damage (i.e. avoid imaging studies with contrast media).

If clinicians could be informed early that a patient is at minimal risk for AKI, they could deploy timely and optimal diagnostic and treatment procedures for the underlying disease of the patient without major concerns for causing or exacerbating kidney damage

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Diagnostic test: Urine-TIMP-IGFBP7 biomarker for AKI

Detailed Description

In patients with acute diseases, it is mandatory for ED Physicians to immediately detect the presence of AKI or exclude; but unfortunately Serum creatinine (SCr) variations (based on KDIGO or AKIN criteria), take 24 to 48 hours to manifest the presence of acute renal ongoing damage. AKI is currently, infact, defined as an increase in SCr of 1.5-fold from baseline within 24 to 48 hours, and decrease in diuresis from admission in hospitalization, using KDIGO.

As consequence, similarly to other biomarkers, such as troponins in acute coronary syndrome and D-dimer in pulmonary embolism, a laboratory test to rule in or rule out AKI is needed in critical patients in ED and our primary objective would be to evaluate the role of urine TIMP-IGFBP7 in this setting.

Primary Objective of the BRAVA Study would be to evaluate the role of the urine biomarkers TIMP-IGFBP7 in predicting the occurrence of AKI in patients presenting to ED with different acute diseases and need for hospitalization.

• Study Type: Observational
• Enrollment (Actual): 818

Contacts and Locations

Study Locations

• Australia
  • Sidney, Australia, NSW2031
    • Prince of Wales Hospital
• India
  • Hyderabad, India, 500003
    • Yashoda Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Rhamathibody Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients presenting to the ED who are determined to be at high risk for AKI.

Description

Patient Inclusion Criteria

• Age ≥ 21 years
• >30% risk of developing AKI based on treating physicians' clinical evaluation AND/OR Presence of ONE OF the following conditions:
• Suspected or confirmed sepsis.
• Acute decompensated heart failure.
• Prolonged gastrointestinal losses from vomiting or diarrhea
• Major trauma
• Major bleeding (e.g. gastrointestinal, pulmonary, genitourinary)
• Severe burns
• Diabetic crisis (DKA, HHS)
• Decompensated liver cirrhosis
• Acute coronary syndrome
• Emergent need for iodinated contrast studies
• Shock from any cause

Patient Exclusion Criteria

• Age < 21 years.
• Unable to give informed consent
• Undergoing hemodialysis or peritoneal dialysis
• Pregnancy
• Terminal illness with < 6 months prognosis
• Do-not-resuscitate status

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Diagnostic performance of urine TIMP-IGFBP7 as early biomarker in ruling in or ruling out acute kidney damage in patients presenting to ED with acute diseases.	48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall length in days of hospital stay	30 hours
Incidence of chronic kidney disease (CKD)	30 days
Overall mortality	30 days
Regional (different countries in Asia Pacific Region) incidence of AKI in a cohort of patients presenting to the ED with acute diseases	48 hours

Collaborators and Investigators

• Sponsor: GREAT Network Italy
• Investigators: Study Director: Salvatore Di Somma, GREAT Network Italy

Publications and helpful links

General Publications

• Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Aug;41(8):1411-23. doi: 10.1007/s00134-015-3934-7. Epub 2015 Jul 11.
• Ostermann M, Joannidis M. Acute kidney injury 2016: diagnosis and diagnostic workup. Crit Care. 2016 Sep 27;20(1):299. doi: 10.1186/s13054-016-1478-z.
• Wetz AJ, Richardt EM, Wand S, Kunze N, Schotola H, Quintel M, Brauer A, Moerer O. Quantification of urinary TIMP-2 and IGFBP-7: an adequate diagnostic test to predict acute kidney injury after cardiac surgery? Crit Care. 2015 Jan 6;19(1):3. doi: 10.1186/s13054-014-0717-4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2018
• Primary Completion (ACTUAL): June 30, 2019
• Study Completion (ACTUAL): November 30, 2019

Study Registration Dates

• First Submitted: November 12, 2018
• First Submitted That Met QC Criteria: November 26, 2018
• First Posted (ACTUAL): November 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 9, 2021
• Last Update Submitted That Met QC Criteria: March 8, 2021
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Emergency Department; Biomarkers; AKI; Urine TIMP-IGFBP7
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury; Acute Disease
• Other Study ID Numbers: BRAVA Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make IPD available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No