Recombinant Human Brain Natriuretic Peptide for the Recovery Stage of Septic Shock (rh-BNP-RSS)

Recombinant Human Brain Natriuretic Peptide for the Recovery Stage of Septic Shock: An Interventional Pilot Study

As infection control improves and circulation stabilizes, treatment de-escalation of septic shock begins, accompanied by fluid redistribution from interstitial spaces to the vasculature, increasing cardiac volume load. Synthetic recombinant human BNP (rh-BNP) plays a role in inducing vasodilation, particularly in the venous system, alleviating cardiac congestion, and enhancing natriuresis and diuresis. Thus the investigators designed a single-center, prospective physiological study to evaluate the efficacy of standard rh-BNP infusion in reducing venous return and enhancing fluid removal, with a secondary objective of assessing the maintenance of perfusion pressure and tissue perfusion.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis-induced Cardiomyopathy; the Recovery Phase of Septic Shock
• Intervention / Treatment: Drug: Lyophilized Recombinant Human Brain Natriuretic Peptide

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lingai Pan, MD; Phone Number: 17708130236; Email: panlingai2004@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Age >18 years.

2. Septic shock in recovery phase with decreasing vasopressor requirements, which is defined as:

   1. Fulfilling the Sepsis-3 definition of septic shock at initial stage.
   2. Hemodynamic stability achieved after adequate initial resuscitation and individualized hemodynamic optimization.
   3. Controlled infection source with 48-hour trend of improving temperature, white blood cell count, and procalcitonin.
   4. 48-hour trend of decreasing vasopressor requirements and transition to negative fluid balance.
   5. Adequate perfusion with warm extremities, and capillary refill time <3 seconds.
3. Ongoing pulse index continuous cardiac output (PiCCO) hemodynamic monitoring and sinus rhythm.
4. Volume indicators above the lower limit of normal range, with global end-diastolic volume index (GEDI) >680 mL/m2 and central venous pressure (CVP) >8 mmHg.
5. Signs of cardiac dysfunction: BNP>200[10] or NT-proBNP >900 pg/ml[6] or reduced ejection fraction (LVEF) < 50%.
6. No bolus dose of diuretics had been administered in the previous 6 hours.
7. Informed consent obtained from patient/legal representative.

Exclusion Criteria:

1. Pregnancy or lactation.
2. Arrhythmia.
3. Advanced renal dysfunction (Acute Kidney Injury [AKI] stage 3 or Chronic Kidney Disease [CKD] stage 3b or higher) based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria.
4. Inadequate ultrasound window preventing acquisition of diagnostic-quality images.
5. Trauma or neurological diseases (including intracerebral hemorrhage and cerebral infarction).
6. Pre-existing severe heart failure (New York Heart Association [NYHA] class III-IV) or acute myocardial infarction within the past 30 days.
7. Concurrent enrollment in interventional trials that could confound study outcomes.

Criteria for withdrawing from the study:

1. Withdrawal of the informed consent.
2. Severe hemodynamic deterioration necessitating the discontinuation of all vasodilatory medications.
3. Treating clinician's decision.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: rh-BNP arm; rh-BNP is reconstituted to a concentration of 10 μg/mL and administered as an initial intravenous bolus of 2 μg/kg over 15 minutes, followed by a continuous infusion at a rate of 0.01 μg/kg/min. Patients should receive at least the first 500μg dose infusion, with a recommended duration of 72 hours. The specific timing of discontinuation will be determined by the attending physician.

Drug: Lyophilized Recombinant Human Brain Natriuretic Peptide; rh-BNP is reconstituted to a concentration of 10 μg/mL and administered as an initial intravenous bolus of 2 μg/kg over 15 minutes, followed by a continuous infusion at a rate of 0.01 μg/kg/min. Patients should receive at least the first 500μg dose infusion, with a recommended duration of 72 hours. The specific timing of discontinuation will be determined by the attending physician. Prior to rh-BNP administration, measure: PiCCO indices, hemodynamic parameters, venous return, tissue perfusion, echocardiographic parameters, ultrasound indices, 2-hour averaged urine output and fluid balance. Repeat all above-mentioned measurements at 30 minutes post-initiation.; Other Names: S20050033

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pressure gradient of venous return	Pmsf - CVP	From baseline to 30 minutes after rh-BNP initiation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perfusion pressure	Absolute and relative changes in perfusion pressure (MAP - CVP)	From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.
CVP	Absolute and relative changes in CVP	From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.
GEDI and global and left-ventricular preload (LVEDV)	Absolute and relative changes in GEDI and global and left-ventricular preload (LVEDV)	From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.
Renal microvascular resistance	Absolute and relative changes in renal microvascular resistance	From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.
Lactate clearance	Absolute and relative changes in lactate clearance	From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.
Duration of invasive mechanical ventilation	Duration of invasive mechanical ventilation	From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.
ICU lengths of stay	ICU lengths of stay	From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety outcome	The safety outcome was hemodynamic instability, defined as a sustained (≥15 minutes) decrease in systolic blood pressure ≥ 10 mmHg or MAP ≥ 5 mmHg compared with baseline, or a requirement for ≥ 0.1 µg/kg/min increase in norepinephrine to maintain MAP ≥ 65 mmHg.	From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.

Collaborators and Investigators

• Sponsor: Sichuan Provincial People's Hospital
• Collaborators: Tibet Kangzhe Pharmaceutical Development Co., Ltd
• Investigators: Principal Investigator: Lingai Pan, MD, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): December 20, 2024

Study Record Updates

• Last Update Posted (Actual): July 29, 2025
• Last Update Submitted That Met QC Criteria: July 23, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Cardiomyopathies; Shock; Shock, Septic; Physiological Effects of Drugs; Natriuretic Agents; Natriuretic Peptide, Brain
• Other Study ID Numbers: 2024-653-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No