A Study of THR-184 in Patients at Risk of Developing Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI)
Condition: Acute Kidney Injury
MeSH terms: Acute Kidney Injury; Wounds and Injuries
Study type: Interventional
Phase: Phase 2

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 description: 
      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) will consist of one 60-minute IV infusion administered
      prior to surgery, followed by a 60-minute IV infusion administered, beginning in the early
      post-operative period, and followed by two (2) additional 60-minute IV infusions
      administered, on consecutive days post-cardiac surgery.

      The primary endpoint for the evaluation of efficacy in patients receiving THR-184, as
      compared to patients receiving Placebo, will be the proportion of patients developing CSA-AKI
      as measured by the Kidney Disease Improving Global Outcomes (KDIGO) criteria, as follows:

        -  Increase in Serum creatinine (SCr) by ≥0.3 mg/dl (>26.5 µmol/l) within 48 hours
           post-surgery; or

        -  Increase in SCr to ≥1.5 times a baseline which has been measured in the previous 7 days;
           or

        -  Urine volume <0.5 ml/kg/h for 6 hours post-operatively

      If at least one of these measures is present by the 7 day assessment, a patient will be
      considered to have developed CSA-AKI.
    

Intervention name(s): THR-184; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): THR-184 is a synthetic oligopeptide administered intravenously.; A normal saline solution identical in appearance to the active drug solution
Other intervention name(s): Synthetic oligopeptide; Saline solution
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Acute Kidney Injury; AKI; Cardiac surgery