AKI - Acute Kidney InjuryPhase 4PROTECT-CSNCT07617675
rhBNP for Prevention of Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI)
A Phase 4 study testing Recombinant Human Brain Natriuretic Peptide (rhBNP) in people with AKI - Acute Kidney Injury and Cardiac Surgical Procedures, run by China National Center for Cardiovascular Diseases at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AKI - Acute Kidney Injury, Cardiac Surgical Procedures, Cardiopulmonary Bypass
- What is being tested?
- Recombinant Human Brain Natriuretic Peptide (rhBNP)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 694 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2026to 31 Jul 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Heng Zhang, MD contact
China1 site
Fuwai Hospital, Chinese Academy of Medical Sciences
Beijing
Sheng Liu, MD, +86-10-88392313
About this study
Official title: 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.
Read the detailed description
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.
- Being tested
- Recombinant Human Brain Natriuretic Peptide (rhBNP), Normal Saline (Placebo)
- 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
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Normal Saline (Placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: Within 72 hours after surgery
Duration of AKI by KDIGO criteria
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.
Measured: Within 7 days after surgery, or until hospital discharge if earlier
Severity of AKI by KDIGO stage
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.
Measured: Within 7 days after surgery, or until hospital discharge if earlier
Incidence of any form of renal replacement therapy (RRT) 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.
Measured: During the index hospitalization
Change in serum creatinine from preoperative baseline
Baseline defined as the last preoperative laboratory result.
Measured: 6, 24, 48, and 120 hours and 7 days after surgery
Change in urinary creatinine from preoperative baseline
Baseline defined as the last preoperative laboratory result.
Measured: 6, 24, 48, and 120 hours and 7 days after surgery
Change in estimated glomerular filtration rate (eGFR) from preoperative baseline
Baseline defined as the last preoperative laboratory result.
Measured: 6, 24, 48, and 120 hours and 7 days after surgery
Change in pulmonary capillary wedge pressure (PCWP) from post-surgical baseline
Baseline defined as the first measurement obtained after completion of surgery.
Measured: 6, 12, 24, and 48 hours after surgery
Change in central venous pressure (CVP) from post-surgical baseline
Baseline defined as the first measurement obtained after completion of surgery.
Measured: 6, 12, 24, and 48 hours after surgery
Change in cardiac output (CO) from post-surgical baseline
Baseline defined as the first measurement obtained after completion of surgery.
Measured: 6, 12, 24, and 48 hours after surgery
Change in cardiac index (CI) from post-surgical baseline
Baseline defined as the first measurement obtained after completion of surgery.
Measured: 6, 12, 24, and 48 hours after surgery
Total intraoperative and postoperative diuretic dose
Cumulative dose of diuretic agents administered intraoperatively and postoperatively, reported by drug.
Measured: From anesthetic induction until hospital discharge
Total intraoperative and postoperative inotrope dose
Cumulative dose of inotropic agents administered intraoperatively and postoperatively, reported by drug.
Measured: From anesthetic induction until hospital discharge
Total intraoperative and postoperative vasopressor dose
Cumulative dose of vasopressor agents administered intraoperatively and postoperatively, reported by drug.
Measured: From anesthetic induction until hospital discharge
Total intraoperative and postoperative vasodilator dose
Cumulative dose of vasodilator agents administered intraoperatively and postoperatively, reported by drug.
Measured: From anesthetic induction until hospital discharge
Major Adverse Kidney Events at 30 days (MAKE-30)
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.
Measured: 30 days after surgery
Major Adverse Kidney Events at 90 days (MAKE-90)
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.
Measured: 90 days after surgery
All-cause mortality at 30 days
Measured: 30 days after surgery
Total ICU length of stay
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.
Measured: Postoperative (From ICU admission until ICU discharge, an average of 3 days)
Postoperative hospital length of stay during the index hospitalization
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.
Measured: Postoperative (From the day of surgery until hospital discharge, an average of 7 days)
Total postoperative medical costs during the index hospitalization
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.
Measured: Postoperative (From the day of surgery until hospital discharge, an average of 7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2026
- Study start1 May 2026 (estimated)
- Primary completion31 Jan 2028 (estimated)
- Study completion31 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for AKI - Acute Kidney InjuryStudies of the same condition, open and under way.
- More trials run by China National Center for Cardiovascular DiseasesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 694 participants (estimated)
Sponsor and investigators
- Sponsor type
- Other government
- Collaborators
- The First Affiliated Hospital of Xiamen University, Guangdong Provincial People's Hospital, Yantai Yuhuangding Hospital, Second Xiangya Hospital of Central South University, First Affiliated Hospital of Chongqing Medical University, Shenzhen Sun Yat-sen Cardiovascular Hospital
- Responsible party
- Sponsor
- Investigators
- Sheng Liu, Principal investigator, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07617675
- Sponsor's protocol ID
- 2026-3155
- Acronym
- PROTECT-CS
- Status last verified
- Apr 2026
- First submitted
- 14 May 2026
- Last updated
- 1 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, Bart BA, Bull DA, Stehlik J, LeWinter MM, Konstam MA, Huggins GS, Rouleau JL, O'Meara E, Tang WH, Starling RC, Butler J, Deswal A, Felker GM, O'Connor CM, Bonita RE, Margulies KB, Cappola TP, Ofili EO, Mann DL, Davila-Roman VG, McNulty SE, Borlaug BA, Velazquez EJ, Lee KL, Shah MR, Hernandez AF, Braunwald E, Redfield MM; NHLBI Heart Failure Clinical Research Network. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA. 2013 Dec 18;310(23):2533-43. doi: 10.1001/jama.2013.282190.
PubMed 24247300Shao J, Wang L, Shao C, Wang Y, Li J, Luo J, Du Z, Hou X. Effects of Perioperative Recombinant Human Brain Natriuretic Peptide in Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis. Rev Cardiovasc Med. 2025 Sep 18;26(9):36423. doi: 10.31083/RCM36423. eCollection 2025 Sep.
PubMed 41089773Perez-Fernandez X, Ulsamer A, Camara-Rosell M, Sbraga F, Boza-Hernandez E, Moret-Ruiz E, Plata-Menchaca E, Santiago-Bautista D, Boronat-Garcia P, Gumucio-Sanguino V, Penafiel-Munoz J, Camacho-Perez M, Betbese-Roig A, Forni L, Campos-Gomez A, Sabater-Riera J; SIRAKI02 Study Group. Extracorporeal Blood Purification and Acute Kidney Injury in Cardiac Surgery: The SIRAKI02 Randomized Clinical Trial. JAMA. 2024 Nov 5;332(17):1446-1454. doi: 10.1001/jama.2024.20630.
PubMed 39382234Shehabi Y, Balachandran M, Al-Bassam W, Bailey M, Bellomo R, Bihari S, Brown A, Brown A, Collins D, Darlison PR, Li MA, Mandarano R, Sarode V, Pakavakis A; ALBICS AKI Study Investigators. Postoperative 20% Albumin Infusion and Acute Kidney Injury in High-Risk Cardiac Surgery Patients: The ALBICS AKI Randomized Clinical Trial. JAMA Surg. 2025 Aug 1;160(8):835-844. doi: 10.1001/jamasurg.2025.1683.
PubMed 40498523Thielmann M, Corteville D, Szabo G, Swaminathan M, Lamy A, Lehner LJ, Brown CD, Noiseux N, Atta MG, Squiers EC, Erlich S, Rothenstein D, Molitoris B, Mazer CD. Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study. Circulation. 2021 Oct 5;144(14):1133-1144. doi: 10.1161/CIRCULATIONAHA.120.053029. Epub 2021 Sep 3.
PubMed 34474590Jia P, Ji Q, Zou Z, Zeng Q, Ren T, Chen W, Yan Z, Shen D, Li Y, Peng F, Su Y, Xu J, Shen B, Luo Z, Wang C, Ding X. Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial. Circulation. 2024 Oct 22;150(17):1366-1376. doi: 10.1161/CIRCULATIONAHA.124.071408. Epub 2024 Sep 25.
PubMed 39319450Landoni 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.
PubMed 38865168Chen HH, Sundt TM, Cook DJ, Heublein DM, Burnett JC Jr. Low dose nesiritide and the preservation of renal function in patients with renal dysfunction undergoing cardiopulmonary-bypass surgery: a double-blind placebo-controlled pilot study. Circulation. 2007 Sep 11;116(11 Suppl):I134-8. doi: 10.1161/CIRCULATIONAHA.106.697250.
PubMed 17846293Mentzer RM Jr, Oz MC, Sladen RN, Graeve AH, Hebeler RF Jr, Luber JM Jr, Smedira NG; NAPA Investigators. Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery:the NAPA Trial. J Am Coll Cardiol. 2007 Feb 13;49(6):716-26. doi: 10.1016/j.jacc.2006.10.048. Epub 2006 Dec 11.
PubMed 17291938Ejaz AA, Martin TD, Johnson RJ, Winterstein AG, Klodell CT, Hess PJ Jr, Ali AK, Whidden EM, Staples NL, Alexander JA, House-Fancher MA, Beaver TM. Prophylactic nesiritide does not prevent dialysis or all-cause mortality in patients undergoing high-risk cardiac surgery. J Thorac Cardiovasc Surg. 2009 Oct;138(4):959-64. doi: 10.1016/j.jtcvs.2009.05.014. Epub 2009 Jul 3.
PubMed 19660420O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, Heizer GM, Komajda M, Massie BM, McMurray JJ, Nieminen MS, Reist CJ, Rouleau JL, Swedberg K, Adams KF Jr, Anker SD, Atar D, Battler A, Botero R, Bohidar NR, Butler J, Clausell N, Corbalan R, Costanzo MR, Dahlstrom U, Deckelbaum LI, Diaz R, Dunlap ME, Ezekowitz JA, Feldman D, Felker GM, Fonarow GC, Gennevois D, Gottlieb SS, Hill JA, Hollander JE, Howlett JG, Hudson MP, Kociol RD, Krum H, Laucevicius A, Levy WC, Mendez GF, Metra M, Mittal S, Oh BH, Pereira NL, Ponikowski P, Tang WH, Tanomsup S, Teerlink JR, Triposkiadis F, Troughton RW, Voors AA, Whellan DJ, Zannad F, Califf RM. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011 Jul 7;365(1):32-43. doi: 10.1056/NEJMoa1100171.
PubMed 21732835Zarbock A, Forni L, Koyner JL, Gomez H, Pannu N, Ostermann M, Bellomo R, Kellum JA, von Groote T. Preventing acute kidney injury and its longer-term impact in the critically ill. Intensive Care Med. 2025 Jul;51(7):1331-1347. doi: 10.1007/s00134-025-08015-8. Epub 2025 Jul 15.
PubMed 40663138Hoste EAJ, Kellum JA, Selby NM, Zarbock A, Palevsky PM, Bagshaw SM, Goldstein SL, Cerda J, Chawla LS. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol. 2018 Oct;14(10):607-625. doi: 10.1038/s41581-018-0052-0.
PubMed 30135570Zarbock A, Weiss R, Albert F, Rutledge K, Kellum JA, Bellomo R, Grigoryev E, Candela-Toha AM, Demir ZA, Legros V, Rosenberger P, Galan Menendez P, Garcia Alvarez M, Peng K, Leger M, Khalel W, Orhan-Sungur M, Meersch M; EPIS-AKI Investigators. Epidemiology of surgery associated acute kidney injury (EPIS-AKI): a prospective international observational multi-center clinical study. Intensive Care Med. 2023 Dec;49(12):1441-1455. doi: 10.1007/s00134-023-07169-7. Epub 2023 Jul 28.
PubMed 37505258Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Nat Rev Dis Primers. 2021 Jul 15;7(1):52. doi: 10.1038/s41572-021-00284-z.
PubMed 34267223
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Recombinant Human Brain Natriuretic Peptide for Renal Protection in Cardiac Surgery: the PROTECT-CS Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07617675
- Acronym / sponsor ID
- PROTECT-CS / 2026-3155
- Keywords
- Recombinant human brain natriuretic peptide, rhBNP, Nesiritide, Acute kidney injury, Cardiac surgery, Cardiopulmonary bypass, Renal protection, Randomized controlled trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 694 participants (estimated)
- Lead sponsor
- China National Center for Cardiovascular DiseasesOther government
- Collaborators
- The First Affiliated Hospital of Xiamen University, Guangdong Provincial People's Hospital, Yantai Yuhuangding Hospital, Second Xiangya Hospital of Central South University, First Affiliated Hospital of Chongqing Medical University, Shenzhen Sun Yat-sen Cardiovascular Hospital
- Study start
- 1 May 2026 (estimated)
- Primary completion
- 31 Jan 2028 (estimated)
- Study completion
- 31 Jul 2029 (estimated)
- First posted
- 1 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| rhBNP Treatment Group | Experimental | Drug: Recombinant Human Brain Natriuretic Peptide (rhBNP)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. |
| Placebo Control Group | Placebo comparator | Drug: Normal Saline (Placebo)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | rhBNP Treatment Group |
| 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. | Drug | Placebo Control Group |
Primary outcome
Incidence of acute kidney injury (AKI) within 7 days postoperatively, diagnosed per KDIGO criteria
Time frame: 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.
21 secondary outcomes
Incidence of AKI within 72 hours postoperatively, diagnosed according to KDIGO criteria
Time frame: Within 72 hours after surgery
Duration of AKI by KDIGO criteria
Time frame: Within 7 days after surgery, or until hospital discharge if earlier
Severity of AKI by KDIGO stage
Time frame: Within 7 days after surgery, or until hospital discharge if earlier
Incidence of any form of renal replacement therapy (RRT) during the index hospitalization
Time frame: During the index hospitalization
Change in serum creatinine from preoperative baseline
Time frame: 6, 24, 48, and 120 hours and 7 days after surgery
Change in urinary creatinine from preoperative baseline
Time frame: 6, 24, 48, and 120 hours and 7 days after surgery
Change in estimated glomerular filtration rate (eGFR) from preoperative baseline
Time frame: 6, 24, 48, and 120 hours and 7 days after surgery
Change in pulmonary capillary wedge pressure (PCWP) from post-surgical baseline
Time frame: 6, 12, 24, and 48 hours after surgery
Change in central venous pressure (CVP) from post-surgical baseline
Time frame: 6, 12, 24, and 48 hours after surgery
Change in cardiac output (CO) from post-surgical baseline
Time frame: 6, 12, 24, and 48 hours after surgery
Change in cardiac index (CI) from post-surgical baseline
Time frame: 6, 12, 24, and 48 hours after surgery
Total intraoperative and postoperative diuretic dose
Time frame: From anesthetic induction until hospital discharge
Total intraoperative and postoperative inotrope dose
Time frame: From anesthetic induction until hospital discharge
Total intraoperative and postoperative vasopressor dose
Time frame: From anesthetic induction until hospital discharge
Total intraoperative and postoperative vasodilator dose
Time frame: From anesthetic induction until hospital discharge
Major Adverse Kidney Events at 30 days (MAKE-30)
Time frame: 30 days after surgery
Major Adverse Kidney Events at 90 days (MAKE-90)
Time frame: 90 days after surgery
All-cause mortality at 30 days
Time frame: 30 days after surgery
Total ICU length of stay
Time frame: Postoperative (From ICU admission until ICU discharge, an average of 3 days)
Postoperative hospital length of stay during the index hospitalization
Time frame: Postoperative (From the day of surgery until hospital discharge, an average of 7 days)
Total postoperative medical costs during the index hospitalization
Time frame: Postoperative (From the day of surgery until hospital discharge, an average of 7 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
- Background: PubMed 24247300Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, Bart BA, Bull DA, Stehlik J, LeWinter MM, Konstam MA, Huggins GS, Rouleau JL, O'Meara E, Tang WH, Starling RC, Butler J, Deswal A, Felker GM, O'Connor CM, Bonita RE, Margulies KB, Cappola TP, Ofili EO, Mann DL, Davila-Roman VG, McNulty SE, Borlaug BA, Velazquez EJ, Lee KL, Shah MR, Hernandez AF, Braunwald E, Redfield MM; NHLBI Heart Failure Clinical Research Network. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA. 2013 Dec 18;310(23):2533-43. doi: 10.1001/jama.2013.282190.
- Background: PubMed 41089773Shao J, Wang L, Shao C, Wang Y, Li J, Luo J, Du Z, Hou X. Effects of Perioperative Recombinant Human Brain Natriuretic Peptide in Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis. Rev Cardiovasc Med. 2025 Sep 18;26(9):36423. doi: 10.31083/RCM36423. eCollection 2025 Sep.
- Background: PubMed 39382234Perez-Fernandez X, Ulsamer A, Camara-Rosell M, Sbraga F, Boza-Hernandez E, Moret-Ruiz E, Plata-Menchaca E, Santiago-Bautista D, Boronat-Garcia P, Gumucio-Sanguino V, Penafiel-Munoz J, Camacho-Perez M, Betbese-Roig A, Forni L, Campos-Gomez A, Sabater-Riera J; SIRAKI02 Study Group. Extracorporeal Blood Purification and Acute Kidney Injury in Cardiac Surgery: The SIRAKI02 Randomized Clinical Trial. JAMA. 2024 Nov 5;332(17):1446-1454. doi: 10.1001/jama.2024.20630.
- Background: PubMed 40498523Shehabi Y, Balachandran M, Al-Bassam W, Bailey M, Bellomo R, Bihari S, Brown A, Brown A, Collins D, Darlison PR, Li MA, Mandarano R, Sarode V, Pakavakis A; ALBICS AKI Study Investigators. Postoperative 20% Albumin Infusion and Acute Kidney Injury in High-Risk Cardiac Surgery Patients: The ALBICS AKI Randomized Clinical Trial. JAMA Surg. 2025 Aug 1;160(8):835-844. doi: 10.1001/jamasurg.2025.1683.
- Background: PubMed 34474590Thielmann M, Corteville D, Szabo G, Swaminathan M, Lamy A, Lehner LJ, Brown CD, Noiseux N, Atta MG, Squiers EC, Erlich S, Rothenstein D, Molitoris B, Mazer CD. Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study. Circulation. 2021 Oct 5;144(14):1133-1144. doi: 10.1161/CIRCULATIONAHA.120.053029. Epub 2021 Sep 3.
- Background: PubMed 39319450Jia P, Ji Q, Zou Z, Zeng Q, Ren T, Chen W, Yan Z, Shen D, Li Y, Peng F, Su Y, Xu J, Shen B, Luo Z, Wang C, Ding X. Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial. Circulation. 2024 Oct 22;150(17):1366-1376. doi: 10.1161/CIRCULATIONAHA.124.071408. Epub 2024 Sep 25.
- Background: PubMed 38865168Landoni 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.
- Background: PubMed 17846293Chen HH, Sundt TM, Cook DJ, Heublein DM, Burnett JC Jr. Low dose nesiritide and the preservation of renal function in patients with renal dysfunction undergoing cardiopulmonary-bypass surgery: a double-blind placebo-controlled pilot study. Circulation. 2007 Sep 11;116(11 Suppl):I134-8. doi: 10.1161/CIRCULATIONAHA.106.697250.
- Background: PubMed 17291938Mentzer RM Jr, Oz MC, Sladen RN, Graeve AH, Hebeler RF Jr, Luber JM Jr, Smedira NG; NAPA Investigators. Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery:the NAPA Trial. J Am Coll Cardiol. 2007 Feb 13;49(6):716-26. doi: 10.1016/j.jacc.2006.10.048. Epub 2006 Dec 11.
- Background: PubMed 19660420Ejaz AA, Martin TD, Johnson RJ, Winterstein AG, Klodell CT, Hess PJ Jr, Ali AK, Whidden EM, Staples NL, Alexander JA, House-Fancher MA, Beaver TM. Prophylactic nesiritide does not prevent dialysis or all-cause mortality in patients undergoing high-risk cardiac surgery. J Thorac Cardiovasc Surg. 2009 Oct;138(4):959-64. doi: 10.1016/j.jtcvs.2009.05.014. Epub 2009 Jul 3.
- Background: PubMed 21732835O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, Heizer GM, Komajda M, Massie BM, McMurray JJ, Nieminen MS, Reist CJ, Rouleau JL, Swedberg K, Adams KF Jr, Anker SD, Atar D, Battler A, Botero R, Bohidar NR, Butler J, Clausell N, Corbalan R, Costanzo MR, Dahlstrom U, Deckelbaum LI, Diaz R, Dunlap ME, Ezekowitz JA, Feldman D, Felker GM, Fonarow GC, Gennevois D, Gottlieb SS, Hill JA, Hollander JE, Howlett JG, Hudson MP, Kociol RD, Krum H, Laucevicius A, Levy WC, Mendez GF, Metra M, Mittal S, Oh BH, Pereira NL, Ponikowski P, Tang WH, Tanomsup S, Teerlink JR, Triposkiadis F, Troughton RW, Voors AA, Whellan DJ, Zannad F, Califf RM. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011 Jul 7;365(1):32-43. doi: 10.1056/NEJMoa1100171.
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- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Heng Zhang, MD contact
Sheng Liu principal investigator
Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Recombinant Human Brain Natriuretic Peptide (rhBNP) in people with AKI - Acute Kidney Injury and Cardiac Surgical Procedures, run by China National Center for Cardiovascular Diseases at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sheng Liu, MD (+86-10-88392313, liusheng@fuwai.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of acute kidney injury (AKI) within 7 days postoperatively, diagnosed per KDIGO criteria (time frame: Within 7 days after surgery, or until hospital discharge if earlier). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07617675, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.