rhBNP for Prevention of Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI)

NCT07617675 | Not Yet Recruiting Phase 4

• 1 other identifier: 2026-3155
• Study Type: interventional
• Target: 694
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious perioperative complication, independently associated with prolonged hospitalization, increased mortality, and progression to chronic kidney disease. Despite advances in surgical techniques and postoperative care, no widely accepted pharmacological prevention strategy exists. Recombinant human brain natriuretic peptide (rhBNP) exerts vasodilatory, diuretic, and natriuretic effects, reduces cardiac preload and afterload, and has demonstrated safety and efficacy in treating congestive heart failure. Preliminary studies suggest rhBNP may reduce postoperative serum creatinine, increase urine output, and improve renal outcomes; however, large-scale randomized controlled evidence is lacking. The PROTECT-CS trial is a multicenter, prospective, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of perioperative continuous intravenous rhBNP infusion (0.01 μg/kg/min for 48 ± 2 hours) for prevention of AKI in high-risk patients undergoing cardiac surgery with cardiopulmonary bypass. A total of 694 participants will be enrolled across 7 centers in China.

Conditions

AKI - Acute Kidney Injury; Cardiac Surgical Procedures; Cardiopulmonary Bypass

Keywords

Recombinant human brain natriuretic peptide; rhBNP; Nesiritide; Acute kidney injury; Cardiac surgery; Cardiopulmonary bypass; Renal protection; Randomized controlled trial; Cardiac surgery-associated acute kidney injury; CSA-AKI

Outcome Measures

Primary Outcomes (1)

• Incidence of acute kidney injury (AKI) within 7 days postoperatively, diagnosed per KDIGO criteria

  AKI defined per KDIGO 2012 criteria as any of: (1) serum creatinine increase ≥ 0.3 mg/dL (≥ 26.5 μmol/L) within 48 hours; (2) serum creatinine increase to ≥ 1.5 times baseline within 7 days; or (3) urine output \< 0.5 mL/kg/h for ≥ 6 consecutive hours. If a participant is discharged earlier than postoperative day 7, AKI events occurring in-hospital are recorded.

  Within 7 days after surgery, or until hospital discharge if earlier

Secondary Outcomes (21)

• Incidence of AKI within 72 hours postoperatively, diagnosed according to KDIGO criteria

  Within 72 hours after surgery

• Duration of AKI by KDIGO criteria

  Within 7 days after surgery, or until hospital discharge if earlier

• Severity of AKI by KDIGO stage

  Within 7 days after surgery, or until hospital discharge if earlier

• Incidence of any form of renal replacement therapy (RRT) during the index hospitalization

  During the index hospitalization

• Change in serum creatinine from preoperative baseline

  6, 24, 48, and 120 hours and 7 days after surgery

Study Arms (2)

rhBNP Treatment Group

EXPERIMENTAL

Participants receive continuous intravenous infusion of recombinant human brain natriuretic peptide (rhBNP) at 0.01 μg/kg/min, initiated from anesthetic induction to the onset of cardiopulmonary bypass, administered continuously for 48 ± 2 hours. All participants receive standard perioperative cardiac surgical care.

Drug: Recombinant Human Brain Natriuretic Peptide (rhBNP)

Placebo Control Group

PLACEBO COMPARATOR

Participants receive continuous intravenous infusion of normal saline at an equivalent rate and volume, initiated from anesthetic induction to the onset of cardiopulmonary bypass, administered continuously for 48 ± 2 hours. All participants receive standard perioperative cardiac surgical care.

Drug: Normal Saline (Placebo)

Interventions

Recombinant Human Brain Natriuretic Peptide (rhBNP) DRUG

Continuous intravenous infusion of rhBNP at 0.01 μg/kg/min, initiated at anesthetic induction and continued for 48 ± 2 hours. The infusion rate is consistent with the approved dosage range in the drug prescribing information.

rhBNP Treatment Group

Normal Saline (Placebo) DRUG

Continuous intravenous infusion of normal saline at an equivalent volume and rate to the rhBNP arm, initiated at anesthetic induction and continued for 48 ± 2 hours.

Placebo Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Scheduled (elective) cardiac surgery requiring cardiopulmonary bypass
• Presence of at least one of the following AKI risk factors:
• Age ≥ 70 years
• Preoperative renal impairment (eGFR ≤ 60 mL/min/1.73 m² or urine protein ≥ +2 at screening)
• Type 2 diabetes mellitus
• Heart failure, defined as NYHA Class II-IV with NT-proBNP ≥ 125 pg/mL at screening; for participants with atrial fibrillation, NT-proBNP ≥ 365 pg/mL is required
• Able to understand and provide written informed consent, and willing and able to comply with all study protocol requirements

You may not qualify if:

• Cardiogenic shock
• Severe hypotension (systolic blood pressure ≤ 90 mmHg) at screening
• Restrictive or obstructive cardiomyopathy, pericarditis, or cardiac tamponade
• Preoperative chronic kidney disease stage 4 or higher (eGFR \< 30 mL/min/1.73 m²), or renal instability as judged by the investigator
• Known AKI diagnosed per KDIGO criteria within 48 hours prior to surgery
• Receipt of any form of renal replacement therapy within 30 days prior to surgery
• Use of ventricular assist device, intra-aortic balloon pump, or any other mechanical cardiac support device within 7 days prior to surgery
• Chronic hepatic insufficiency (Child-Pugh Class B or C) or hepatic dysfunction (ALT or AST \> 2× upper limit of normal \[ULN\], or total bilirubin \> 1.5× ULN)
• Active hepatitis B (HBsAg positive with HBV-DNA indicating active viral replication), active hepatitis C (HCV antibody positive with HCV-RNA indicating active viral replication), positive syphilis screen, known HIV infection, or positive HIV test
• Confirmed or treated endocarditis, sepsis, or active infection requiring antibiotic treatment within 30 days prior to surgery
• Requirement for aortic dissection repair, complex congenital heart surgery, emergency surgery, or life-saving surgery
• History of malignant tumor, solid tumor, metastatic tumor, or hematological malignancy within the past 5 years
• Prior organ transplantation or current use of immunosuppressive agents
• Any condition that may conflict with or contraindicate the use of intravenous vasodilator therapy
• Prior adverse reaction to nesiritide (recombinant BNP)

Sponsors & Collaborators

• Shenzhen Sun Yat-sen Cardiovascular Hospital: collaborator
• The First Affiliated Hospital of Xiamen University: collaborator
• Guangdong Provincial People's Hospital: collaborator
• Yantai Yuhuangding Hospital: collaborator
• China National Center for Cardiovascular Diseases: lead
• Second Xiangya Hospital of Central South University: collaborator
• First Affiliated Hospital of Chongqing Medical University: collaborator

Study Sites (1)

Fuwai Hospital, Chinese Academy of Medical Sciences

Beijing, China

Location

Related Publications (15)

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• Landoni G, Monaco F, Ti LK, Baiardo Redaelli M, Bradic N, Comis M, Kotani Y, Brambillasca C, Garofalo E, Scandroglio AM, Viscido C, Paternoster G, Franco A, Porta S, Ferrod F, Calabro MG, Pisano A, Vendramin I, Barucco G, Federici F, Severi L, Belletti A, Cortegiani A, Bruni A, Galbiati C, Covino A, Baryshnikova E, Giardina G, Venditto M, Kroeller D, Nakhnoukh C, Mantovani L, Silvetti S, Licheri M, Guarracino F, Lobreglio R, Di Prima AL, Fresilli S, Labanca R, Mucchetti M, Lembo R, Losiggio R, Bove T, Ranucci M, Fominskiy E, Longhini F, Zangrillo A, Bellomo R; PROTECTION Study Group. A Randomized Trial of Intravenous Amino Acids for Kidney Protection. N Engl J Med. 2024 Aug 22;391(8):687-698. doi: 10.1056/NEJMoa2403769. Epub 2024 Jun 12.

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Related Links

• Related Info

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Sheng Liu

  Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sheng Liu, MD

CONTACT

+86-10-88392313; liusheng@fuwai.com

Heng Zhang, MD

CONTACT

+86-10-88322315

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study drug (rhBNP) and placebo (normal saline) are prepared and labeled by an unblinded nurse who is not involved in patient care or outcome assessment. The prepared syringes are identical in appearance. All participants, treating clinicians, investigators, and outcome assessors remain blinded throughout the trial. Emergency unblinding is permitted in cases of medical necessity (e.g., pregnancy, serious adverse event requiring knowledge of treatment allocation) and must be documented in detail.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Eligible participants are randomized 1:1 to either the rhBNP treatment group or the placebo control group. Both groups receive standard perioperative care. Randomization is performed using a central IWRS, stratified by study center with a block size of 6.

Study Record Dates

• First Submitted: May 14, 2026
• First Posted: June 1, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): July 31, 2029
• Last Updated: June 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

CN (1)