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

Sponsor

Angion Biomedica Corp (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02771509

Collaborator

Everest Clinical Research (Other), CTI Clinical Trial and Consulting Services (Other), Clinical Accelerator (Other)

275

Enrollment

Locations

Arms

53.2

Anticipated Duration (Months)

6.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury	Drug: ANG-3777 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

275 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Feb 24, 2017

Anticipated Primary Completion Date :

Aug 1, 2021

Anticipated Study Completion Date :

Aug 1, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

The mean AUC of the percent increase in serum creatinine above baseline [starting from 24 hr after the end of CPB through Day 6]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
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.

Contacts and Locations

Locations

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