Perioperative Recombinant Human Brain Natriuretic Peptide for Renal Protection in Cardiac Surgery: the PROTECT-CS Randomized Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 694
- 试验地点
- 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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