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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: ANG-3777; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 275
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Botucatu, Brazil, 18618-686
    • Faculdade de Medicina da UNESP Campus de Botucatu
  • Porto Alegre, Brazil, 90040-371
    • Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia (IC - FUC)
  • Ribeirão Preto, Brazil, 14048-900
    • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP)
  • São José Do Rio Preto, Brazil, 15090-000
    • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
  • São Paulo, Brazil, 05403-000
    • Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InCor - HCFMUSP)
• Canada
  • Québec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie et de Pneumologie de Quebec
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • St. John Regional Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Center
    • Toronto, Ontario, Canada, M5B 1W8
      • Saint Michael's Hospital
  • Quebec
    • Montréal, Quebec, Canada, H2W 1T8
      • CHUM - Hotel Dieu
    • Montréal, Quebec, Canada, H4A 3J1
      • MUHC - Royal Victoria Hospital
• Georgia
  • Tbilisi, Georgia, 0159
    • Bokhua Memorial Cardiovascular Center
  • Tbilisi, Georgia, 0112
    • Israeli-Georgian Medical Research Clinic Helsicore
  • Tbilisi, Georgia, 0114
    • New Hospitals LTD
  • Tbilisi, Georgia, 0167
    • Jerarsi JSC
  • Tbilisi, Georgia, 0186
    • Tbilisi Heart Center
  • Tbilisi, Georgia, 0519
    • Acad. G. Chapidze Emergency Cardiology Center
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • San Diego, California, United States, 92123
      • California Institute of Renal Reseach
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School Of Medicine
  • Florida
    • Fleming Island, Florida, United States, 32207
      • Fleming Island Center for Clinical Research
    • Gainesville, Florida, United States, 32610
      • UF Health at Unviersity of Florida
    • Jacksonville, Florida, United States, 32207
      • River City Clinical Research
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Indiana Ohio Heart
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
    • Bethesda, Maryland, United States, 20814
      • Suburban Hospital
  • Michigan
    • Midland, Michigan, United States, 49770
      • MidMichigan Medical Center Midland
    • Petoskey, Michigan, United States, 49770
      • Cardiac & Vascular Research Center of Northern Michigan
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Bryan Heart
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • TriHealth
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Fairview
    • Columbus, Ohio, United States, 43210
      • Ohio State Wexner Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75226
      • Baylor Jack and Jane Hamilton Heart and Vascular center- Soltero Cardiovascular Research Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient is either male or female ≥ 18 years.
2. Patient has provided written informed consent, and is willing and able to comply with the requirements of the study protocol, including screening procedures.

3. Patient must be scheduled for and undergo a non-emergent cardiac surgical procedure involving CPB. Eligible procedures include:

   1. Coronary artery bypass graft (CABG) alone
   2. Aortic valve replacement or repair alone, with or without aortic root repair
   3. Mitral, tricuspid, or pulmonic valve replacement or repair alone
   4. Combined replacement of several cardiac valves
   5. CABG with aortic, mitral, tricuspid, or pulmonic valve replacement or repair
   6. CABG with combined cardiac valve replacement or repair.

4. Patient must have the following risk factor(s) for AKI prior to surgery:

   1. Estimated glomerular filtration rate (eGFR) of ≥ 20 and < 30 ml/min/1.73m2, or
   2. eGFR ≥ 30 and < 60 mL/min/1.73m2 and ONE of the following Additional Risk Factors (other than age ≥ 75 years), or
   3. 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.
5. 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.
6. Patient's body mass index (BMI) < 40 at Screening.

Exclusion Criteria:

1. Patient has eGFR < 20 mL/min/1.73 m2 within 48 hours pre-surgery as measured by MDRD 4.
2. 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.
3. Currently active infection requiring antibiotic treatment.
4. 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.
5. Administration of iodinated contrast material within 24 hours prior to cardiac surgery.
6. Patients diagnosed with AKI as defined by KDIGO criteria within 48 hours prior to surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ANG-3777; 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; 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; Other Names: Hepatocyte growth factor mimetic
Placebo Comparator: Normal Saline; 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; Normal saline; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Angion Biomedica Corp
• Collaborators: CTI Clinical Trial and Consulting Services; Everest Clinical Research; Clinical Accelerator
• Investigators: Study Director: John Neylan, MD, Angion Biomedica

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2017
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: April 18, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (Estimate): May 13, 2016

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: July 9, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Cardiac Surgery; Acute Kidney Injury; CPB
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: 002-15

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No