Clinical Trial: A Study of THR-184 in Patients at Risk of Developing Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi-Center, Parallel-Group, Randomized, Double Blind, Adaptive Study Investigating the Safety and Efficacy of THR-184 in Patients at Increased Risk of Developing Cardiac Surgery Associated-

Brief Summary: The purpose of this study is to determine whether THR-184 when administered around the time of cardiac surgery that requires cardiopulmonary bypass can prevent or ameliorate the development of acute kidney injury.

Detailed Summary:

The study has been designed to include patients scheduled for cardiac surgery who are considered at increased risk for developing CSA-AKI. The eligibility criteria are intended to enrich the study population with such patients.

Stage 1 consisted of 140 patients randomized in a 1:1:1:1 ratio (approximately 35 patients per treatment arm) to Placebo or to one of three (3) THR-184 dose arms:

  • initial pre-surgery low dose of THR-184 by three (3) post-surgery doses at the low dose, or
  • initial pre-surgery middle dose of THR-184 followed by three (3) post-surgery doses at the low dose, or
  • initial pre-surgery high dose of THR-184 followed by three (3) post-surgery doses at the low dose

An interim analysis (IA) was performed by the Independent Statistical Center (ISC) and presented to the Independent Data Monitoring Committee (IDMC). The IDMC indicated no safety concerns and recommended that the study continue with the placebo arm and the initial pre-surgery high dose arm. Additionally, another dosing arm will be added, which will increase the dose post-surgery.

Stage 2 will consist of approximately 270 patients randomized in a 1:1:2 ratio to Placebo or to a dose selected from one of the two (2) THR-184 dose arms:

  • initial pre-surgery high dose of THR-184, followed by (3) post-surgery doses at the original low dose;
  • initial pre-surgery high dose of THR-184, followed by (3) post-surgery doses at ~80% of the pre-surgery dose

Study treatment (THR-184 or placebo)
Sponsor: Thrasos Innovation, Inc.

Current Primary Outcome: Incidence of Acute Kidney Injury (AKI) [ Time Frame: 7 days ]

Acute kidney injury (AKI) is defined using the KDIGO criteria, in which AKI is defined as any of the following:

  • Increase in SCr by ≥0.3 mg/dl (≥26.5 µmol/l) within 48 hours; or
  • Increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or
  • Urine volume <0.5 ml/kg/h for 6 hours.


Original Primary Outcome: Incidence of acute kidney injury (AK) [ Time Frame: 7 days ]

Current Secondary Outcome:

  • Incidence of AKI [ Time Frame: 7 days ]

    AKI is defined using the SCr-KDIGO criteria, defined as the following:

    • Increase in SCr by ≥0.3 mg/dl (≥26.5 µmol/l) within 48 hours; or
    • Increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days.
  • Severity of AKI [ Time Frame: 7 days ]

    AKI is defined using the KDIGO criteria, in which AKI is defined as any of the following:

    • Increase in SCr by ≥0.3 mg/dl (≥26.5 µmol/l) within 48 hours; or
    • Increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or
    • Urine volume <0.5 ml/kg/h for 6 hours.

    Staging of AKI is defined as the following:

    Stage 1: SCr 1.5 - 1.9 times baseline OR ≥0.3 mg/dL (≥26.5 µmol/L) increase, Urine output <0.5 ml/kg/hr for 6-12 hours Stage 2: SCr 2.0-2.9 times baseline, Urine output <0.5 ml/kg/h for ≥ 12 hours Stage 3: SCr 3.0 times baseline OR Increase in SCr to ≥5.0 mg/dL (≥353.6 µmol/L) OR Initiation of renal replacement therapy OR In patients <18 years, decrease in eGFR to <35 ml/min per 1.73 m^2, Urine output <0.3 ml/kg/h for ≥24 hours OR Anuria for ≥12 hours.

    No AKI is considered the best outcome, and Stage 3 the worst outcome.

  • Duration of AKI [ Time Frame: 7 days OR up to discharge after surgery ]
    AKI is defined using the Scr-KDIGO criteria. Duration of AKI is defined as the number of days from start of AKI (SCr-KDIGO) where either SCr increase ≥ 0.3 mg/dL above pre-AKI reference point (if the value exists) or if SCr increase ≥1.5 times baseline or dialysis in the first 7 days up to discharge if prior to 7 days.


Original Secondary Outcome: Maximum change from baseline in serum creatinine [ Time Frame: 7 days ]

Information By: Thrasos Innovation, Inc.

Dates:
Date Received: April 10, 2013
Date Started: May 2013
Date Completion:
Last Updated: March 8, 2017
Last Verified: March 2017