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

29. května 2026 aktualizováno: 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.

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Odhadovaný)

694

Fáze

  • Fáze 4

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

Studijní záloha kontaktů

  • Jméno: Heng Zhang, MD
  • Telefonní číslo: +86-10-88322315

Studijní místa

  • Čína
      • Beijing, Čína
        • Fuwai Hospital, Chinese Academy of Medical Sciences
        • Kontakt:
          • Sheng Liu, MD
          • Telefonní číslo: +86-10-88392313

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dospělý
  • Starší dospělý

Přijímá zdravé dobrovolníky

Ne

Popis

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

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Prevence
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Čtyřnásobek

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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.
Lék: 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.
Komparátor placeba: 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.
Lék: 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.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Incidence of acute kidney injury (AKI) within 7 days postoperatively, diagnosed per KDIGO criteria
Časové okno: 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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Incidence of AKI within 72 hours postoperatively, diagnosed according to KDIGO criteria
Časové okno: Within 72 hours after surgery
Within 72 hours after surgery
Duration of AKI by KDIGO criteria
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 30 days after surgery
30 days after surgery
Total ICU length of stay
Časové okno: 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
Časové okno: 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
Časové okno: 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)

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

China National Center for Cardiovascular Diseases

Spolupracovníci

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

Vyšetřovatelé

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

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Užitečné odkazy

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

1. května 2026

Primární dokončení (Odhadovaný)

31. ledna 2028

Dokončení studie (Odhadovaný)

31. července 2029

Termíny zápisu do studia

První předloženo

14. května 2026

První předloženo, které splnilo kritéria kontroly kvality

29. května 2026

První zveřejněno (Aktuální)

1. června 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

1. června 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

29. května 2026

Naposledy ověřeno

1. dubna 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • 2026-3155

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu 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.

Typ podpůrných informací pro sdílení IPD

  • PROTOKOL STUDY
  • MÍZA
  • ICF

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Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

produkt vyrobený a vyvážený z USA

Ne

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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