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

29 maggio 2026 aggiornato da: China National Center for Cardiovascular Diseases

Perioperative Recombinant Human Brain Natriuretic Peptide for Renal Protection in Cardiac Surgery: the PROTECT-CS Randomized Clinical Trial

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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Acute kidney injury (AKI) is one of the most common and serious complications following cardiac surgery. CSA-AKI is independently associated with short-term adverse outcomes including prolonged ICU stay, increased need for renal replacement therapy, and in-hospital mortality, as well as long-term consequences including progression to chronic kidney disease and elevated cardiovascular mortality. Despite extensive research efforts, current clinical management of CSA-AKI remains largely supportive, and no pharmacological intervention has been established as a standard preventive strategy in international guidelines.

Recombinant human brain natriuretic peptide (rhBNP, generic name: nesiritide) shares structural and biological activity highly similar to endogenous BNP. Its pharmacological properties include arterial and venous vasodilation, promotion of natriuresis and diuresis, reduction of cardiac preload and afterload, and direct improvement of glomerular filtration rate without adversely affecting serum potassium or creatinine. rhBNP has been widely used in Chinese cardiac surgery and critical care centers for perioperative hemodynamic optimization. Published small-sample randomized trials and a recent meta-analysis have suggested potential renal protective benefits of perioperative rhBNP in cardiac surgery patients; however, these studies were limited by small sample sizes, heterogeneous populations, and the use of renal endpoints as exploratory rather than primary outcomes.

The PROTECT-CS trial aims to address this evidence gap. Eligible participants are adults aged ≥18 years scheduled for elective cardiac surgery under cardiopulmonary bypass who have at least one AKI risk factor (age ≥70 years, preoperative renal impairment, type 2 diabetes mellitus, or heart failure). Participants will be randomized 1:1 using a central IWRS system, stratified by study center with a block size of 6, to receive either continuous intravenous rhBNP at 0.01 μg/kg/min or an equivalent volume of normal saline (placebo), initiated from anesthetic induction to the onset of cardiopulmonary bypass and continued for 48 ± 2 hours total. All participants receive standard perioperative care throughout.

The primary endpoint is the incidence of AKI diagnosed per KDIGO criteria within 7 days postoperatively. Secondary endpoints include AKI incidence within 72 hours, AKI duration and severity, need for renal replacement therapy during hospitalization, changes in renal function biomarkers, hemodynamic parameters, diuretic and vasoactive drug use, major adverse kidney events at 30 and 90 days (MAKE-30 and MAKE-90), 30-day all-cause mortality, ICU and hospital length of stay, and total hospitalization costs.

An independent Data Monitoring Committee (DMC) will conduct periodic safety reviews and a pre-planned interim analysis. Adverse drug reactions are graded per NCI-CTCAE Version 5.0. All study data are collected via an electronic data capture (EDC) system and managed in accordance with GCP standards.

Tipo di studio

Interventistico

Iscrizione (Stimato)

694

Fase

  • Fase 4

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

  • Nome: Heng Zhang, MD
  • Numero di telefono: +86-10-88322315

Luoghi di studio

  • Cina
      • Beijing, Cina
        • Fuwai Hospital, Chinese Academy of Medical Sciences
        • Contatto:
          • Sheng Liu, MD
          • Numero di telefono: +86-10-88392313

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • Participation in any other clinical trial within 30 days prior to surgery
  • Pregnant or breastfeeding women
  • Any other condition that, in the judgment of the investigator, renders the participant unsuitable for study participation

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Prevenzione
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: rhBNP Treatment Group
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.
Droga: Recombinant Human Brain Natriuretic Peptide (rhBNP)
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.
Comparatore placebo: Placebo Control Group
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.
Droga: Normal Saline (Placebo)
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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Incidence of acute kidney injury (AKI) within 7 days postoperatively, diagnosed per KDIGO criteria
Lasso di tempo: Within 7 days after surgery, or until hospital discharge if earlier
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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Incidence of AKI within 72 hours postoperatively, diagnosed according to KDIGO criteria
Lasso di tempo: Within 72 hours after surgery
Within 72 hours after surgery
Duration of AKI by KDIGO criteria
Lasso di tempo: Within 7 days after surgery, or until hospital discharge if earlier
Duration of AKI among participants who develop AKI within 7 days postoperatively, recorded in hours from onset to resolution per KDIGO criteria. If a participant is discharged earlier than postoperative day 7, in-hospital AKI events are recorded.
Within 7 days after surgery, or until hospital discharge if earlier
Severity of AKI by KDIGO stage
Lasso di tempo: Within 7 days after surgery, or until hospital discharge if earlier
Distribution of participants across KDIGO Stage 1, Stage 2, and Stage 3, based on the maximum stage reached. If a participant is discharged earlier than postoperative day 7, in-hospital AKI events are recorded.
Within 7 days after surgery, or until hospital discharge if earlier
Incidence of any form of renal replacement therapy (RRT) during the index hospitalization
Lasso di tempo: During the index hospitalization
Number of participants receiving any form of RRT (intermittent hemodialysis, continuous renal replacement therapy, or peritoneal dialysis) during the surgical hospitalization.
During the index hospitalization
Change in serum creatinine from preoperative baseline
Lasso di tempo: 6, 24, 48, and 120 hours and 7 days after surgery
Baseline defined as the last preoperative laboratory result.
6, 24, 48, and 120 hours and 7 days after surgery
Change in urinary creatinine from preoperative baseline
Lasso di tempo: 6, 24, 48, and 120 hours and 7 days after surgery
Baseline defined as the last preoperative laboratory result.
6, 24, 48, and 120 hours and 7 days after surgery
Change in estimated glomerular filtration rate (eGFR) from preoperative baseline
Lasso di tempo: 6, 24, 48, and 120 hours and 7 days after surgery
Baseline defined as the last preoperative laboratory result.
6, 24, 48, and 120 hours and 7 days after surgery
Change in pulmonary capillary wedge pressure (PCWP) from post-surgical baseline
Lasso di tempo: 6, 12, 24, and 48 hours after surgery
Baseline defined as the first measurement obtained after completion of surgery.
6, 12, 24, and 48 hours after surgery
Change in central venous pressure (CVP) from post-surgical baseline
Lasso di tempo: 6, 12, 24, and 48 hours after surgery
Baseline defined as the first measurement obtained after completion of surgery.
6, 12, 24, and 48 hours after surgery
Change in cardiac output (CO) from post-surgical baseline
Lasso di tempo: 6, 12, 24, and 48 hours after surgery
Baseline defined as the first measurement obtained after completion of surgery.
6, 12, 24, and 48 hours after surgery
Change in cardiac index (CI) from post-surgical baseline
Lasso di tempo: 6, 12, 24, and 48 hours after surgery
Baseline defined as the first measurement obtained after completion of surgery.
6, 12, 24, and 48 hours after surgery
Total intraoperative and postoperative diuretic dose
Lasso di tempo: From anesthetic induction until hospital discharge
Cumulative dose of diuretic agents administered intraoperatively and postoperatively, reported by drug.
From anesthetic induction until hospital discharge
Total intraoperative and postoperative inotrope dose
Lasso di tempo: From anesthetic induction until hospital discharge
Cumulative dose of inotropic agents administered intraoperatively and postoperatively, reported by drug.
From anesthetic induction until hospital discharge
Total intraoperative and postoperative vasopressor dose
Lasso di tempo: From anesthetic induction until hospital discharge
Cumulative dose of vasopressor agents administered intraoperatively and postoperatively, reported by drug.
From anesthetic induction until hospital discharge
Total intraoperative and postoperative vasodilator dose
Lasso di tempo: From anesthetic induction until hospital discharge
Cumulative dose of vasodilator agents administered intraoperatively and postoperatively, reported by drug.
From anesthetic induction until hospital discharge
Major Adverse Kidney Events at 30 days (MAKE-30)
Lasso di tempo: 30 days after surgery
Composite endpoint defined as the occurrence of any of the following: death from any cause, receipt of renal replacement therapy, or ≥25% decline in eGFR from baseline.
30 days after surgery
Major Adverse Kidney Events at 90 days (MAKE-90)
Lasso di tempo: 90 days after surgery
Composite endpoint defined as the occurrence of any of the following: death from any cause, receipt of renal replacement therapy, or ≥25% decline in eGFR from baseline.
90 days after surgery
All-cause mortality at 30 days
Lasso di tempo: 30 days after surgery
30 days after surgery
Total ICU length of stay
Lasso di tempo: Postoperative (From ICU admission until ICU discharge, an average of 3 days)
Total ICU length of stay during the index hospitalization, calculated as the difference between ICU exit time and ICU admission time. For participants with multiple ICU admissions, total ICU length of stay is the sum of all individual ICU stays.
Postoperative (From ICU admission until ICU discharge, an average of 3 days)
Postoperative hospital length of stay during the index hospitalization
Lasso di tempo: Postoperative (From the day of surgery until hospital discharge, an average of 7 days)
Postoperative hospital length of stay during the index hospitalization, calculated as the number of days from the date of surgery to the date of hospital discharge. Days of hospitalization before surgery are not included.
Postoperative (From the day of surgery until hospital discharge, an average of 7 days)
Total postoperative medical costs during the index hospitalization
Lasso di tempo: Postoperative (From the day of surgery until hospital discharge, an average of 7 days)
Total postoperative medical costs during the index hospitalization, calculated as the sum of all itemized hospital charges incurred from the date of surgery to the date of hospital discharge (including but not limited to surgical fees, ICU fees, medications, laboratory tests, imaging, nursing care, and bed fees), extracted from the hospital information system (HIS) billing records. Charges incurred before surgery are not included.
Postoperative (From the day of surgery until hospital discharge, an average of 7 days)

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

China National Center for Cardiovascular Diseases

Collaboratori

Guangdong Provincial People's Hospital
Second Xiangya Hospital of Central South University
First Affiliated Hospital of Chongqing Medical University
Yantai Yuhuangding Hospital
The First Affiliated Hospital of Xiamen University
Shenzhen Sun Yat-sen Cardiovascular Hospital

Investigatori

  • Investigatore principale: Sheng Liu, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Pubblicazioni e link utili

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Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 maggio 2026

Completamento primario (Stimato)

31 gennaio 2028

Completamento dello studio (Stimato)

31 luglio 2029

Date di iscrizione allo studio

Primo inviato

14 maggio 2026

Primo inviato che soddisfa i criteri di controllo qualità

29 maggio 2026

Primo Inserito (Effettivo)

1 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

1 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

29 maggio 2026

Ultimo verificato

1 aprile 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 2026-3155

Piano per i dati dei singoli partecipanti (IPD)

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SÌ

Descrizione del piano IPD

De-identified individual participant data (IPD) underlying the results reported in the primary publication will be made available upon reasonable request, after approval by the principal investigator and data access committee, beginning 12 months after publication of the primary results and available for 36 months thereafter. Data will be shared via a secure data transfer platform. Requests should include a methodologically sound proposal and be directed to the principal investigator.

Tipo di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO
  • LINFA
  • ICF

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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