Study to Prevent Acute Kidney Injury After Cardiac Surgery Involving Cardiopulmonary Bypass

Study Overview
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Brief Summary
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The objective of the study is to assess the safety and efficacy of ANG-3777 in preventing AKI compared to placebo when administered to patients at risk for developing acute kidney injury (AKI) following cardiac surgical procedures involving cardiopulmonary bypass (CPB).

Official Title
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A Multicenter, Prospective, Parallel-Group, Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study of ANG-3777 to Assess the Safety and Efficacy of BB3 in Patients Developing Acute Kidney Injury After Cardiac Surgery

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Drug: ANG-3777
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is either male or female ≥ 18 years. Patient has provided written informed consent, and is willing and able to comply with the requirements of the study protocol, including screening procedures. Patient must be scheduled for and undergo a non-emergent cardiac surgical procedure involving CPB. Eligible procedures include: Coronary artery bypass graft (CABG) alone Aortic valve replacement or repair alone, with or without aortic root repair Mitral, tricuspid, or pulmonic valve replacement or repair alone Combined replacement of several cardiac valves CABG with aortic, mitral, tricuspid, or pulmonic valve replacement or repair CABG with combined cardiac valve replacement or repair. Patient must have the following risk factor(s) for AKI prior to surgery: Estimated glomerular filtration rate (eGFR) of ≥ 20 and < 30 ml/min/1.73m2, or eGFR ≥ 30 and < 60 mL/min/1.73m2 and ONE of the following Additional Risk Factors (other than age ≥ 75 years), or eGFR ≥ 60 ml/min/1.73m2 and TWO of the following Additional Risk Factors eGFR will be calculated using the abbreviated MDRD equation (MDRD-4, often referred to as the Levey equation): eGFR = 186.3 x sCr-1.154 x Age-0.203 x [0.742 if Female] x [1.212 if Black] Additional Risk Factors: Combined valve and coronary surgery Previous cardiac surgery with sternotomy Left ventricular ejection fraction (LVEF) < 35% by invasive or noninvasive diagnostic cardiac imaging within 90 days prior to surgery Diabetes mellitus requiring insulin treatment Non-insulin-requiring diabetes with documented presence of at least moderate (+2 or > 100 mg/dL) proteinuria on urine analysis (medical history or dipstick) Documented NYHA Class III or IV within 1 year prior to index surgery Age ≥ 75 years can be considered an Additional Risk Factor only for patients with eGFR ≥ 60 ml/min/1.73m2. Patient must have presented for surgery without prior evidence of active renal injury defined as no acute rise in sCr > 0.3 mg/dL or no 50% increase in sCr between the time of Screening and pre-surgery. Patient's body mass index (BMI) < 40 at Screening. Exclusion Criteria: Patient has eGFR < 20 mL/min/1.73 m2 within 48 hours pre-surgery as measured by MDRD 4. Patient has ongoing sepsis or partially treated infection. Sepsis is defined as the presence of a confirmed pathogen, along with fever or hypoperfusion (i.e., acidosis and new onset elevation of liver function tests) or hypotension requiring pressor use prior to surgery. Currently active infection requiring antibiotic treatment. Patient who has an active (requiring treatment) malignancy or history within 5 years prior to enrollment in the study, of solid, metastatic or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed. Administration of iodinated contrast material within 24 hours prior to cardiac surgery. Patients diagnosed with AKI as defined by KDIGO criteria within 48 hours prior to surgery.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ANG-3777<br>Study drug will be administered for a total of 4 daily intravenous (IV) infusions. The first post-operative dose MUST be started within 4 hours of completing CPB. The second dose will be administered 24 ± 2 hours after completing CPB, and the third and fourth doses will be administered 24 ± 2 hours after each previous dose. Duration of administration is 30 minutes. | Drug: ANG-3777<br>* 6 mg/mL BB3, IV, 4 days in a row, first dose must be within 4 hours after surgery, the next three doses will be approx. 24 hours after the last dose<br>* Other names: Hepatocyte growth factor mimetic;|
| Placebo Comparator: Normal Saline<br>The placebo will be administered for a total of 4 daily intravenous (IV) infusions. The first post-operative dose MUST be started within 4 hours of completing CPB. The second dose will be administered 24 ± 2 hours after completing CPB, and the third and fourth doses will be administered 24 ± 2 hours after each previous dose. Duration of administration is 30 minutes. | Drug: Placebo<br>* Normal saline<br>* Other names: Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean AUC of the percent increase in serum creatinine above baseline |  | starting from 24 hr after the end of CPB through Day 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CPB, Cardiac Surgery, Acute Kidney Injury