Clinical trial NCT01830920
Conditions: Acute Kidney Injury
Keywords: Acute Kidney Injury AKI Cardiac surgery
Sponsor: Thrasos Innovation, Inc.
Start date: 2013-05-01; Completion date: 2015-09-01
Enrollment: 452 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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 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.

Arms: arm 1: An identical appearing placebo will be administered. arm 2: THR-184 initial pre-surgery low dose followed by (3) post surgery doses at the low dose. arm 3: THR-184 initial pre-surgery mid-dose followed by (3) post surgery doses at the low dose. arm 4: THR-184 initial pre-surgery high dose followed by (3) post surgery doses at the low dose. arm 5: THR-184 initial pre-surgery high dose followed by (3) post surgery doses \~80% of the pre-surgery dose.
Interventions: intervention 1: THR-184 intervention 2: Placebo
Intervention descriptions: intervention 1: THR-184 is a synthetic oligopeptide administered intravenously. intervention 2: A normal saline solution identical in appearance to the active drug solution

Protocol documents: