Recombinant Human Brain Natriuretic Peptide for the Recovery Stage of Septic Shock

Official title

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

Overview

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.

Interventions

• 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, e

Primary outcome measures

• The pressure gradient of venous return [Time frame: From baseline to 30 minutes after rh-BNP initiation.]

Secondary outcome measures (7)

• Perfusion pressure [Time frame: From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.]
• CVP [Time frame: From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.]
• GEDI and global and left-ventricular preload (LVEDV) [Time frame: From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.]
• Renal microvascular resistance [Time frame: From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.]
• Lactate clearance [Time frame: From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.]
• Duration of invasive mechanical ventilation [Time frame: From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.]
• ICU lengths of stay [Time frame: From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation.]

Eligibility criteria

Inclusion criteria

• Age >18 years.
• Septic shock in recovery phase with decreasing vasopressor requirements, which is defined as:

• Fulfilling the Sepsis-3 definition of septic shock at initial stage.
• Hemodynamic stability achieved after adequate initial resuscitation and individualized hemodynamic optimization.
• Controlled infection source with 48-hour trend of improving temperature, white blood cell count, and procalcitonin.
• 48-hour trend of decreasing vasopressor requirements and transition to negative fluid balance.
• Adequate perfusion with warm extremities, and capillary refill time <3 seconds.
• Ongoing pulse index continuous cardiac output (PiCCO) hemodynamic monitoring and sinus rhythm.
• 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.
• Signs of cardiac dysfunction: BNP>200\[10\] or NT-proBNP >900 pg/ml\[6\] or reduced ejection fraction (LVEF) < 50%.
• No bolus dose of diuretics had been administered in the previous 6 hours.
• Informed consent obtained from patient/legal representative.

Exclusion criteria

• Pregnancy or lactation.
• Arrhythmia.
• 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.
• Inadequate ultrasound window preventing acquisition of diagnostic-quality images.
• Trauma or neurological diseases (including intracerebral hemorrhage and cerebral infarction).
• Pre-existing severe heart failure (New York Heart Association \[NYHA\] class III-IV) or acute myocardial infarction within the past 30 days.
• Concurrent enrollment in interventional trials that could confound study outcomes.

Criteria for withdrawing from the study:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Luo JC, Mou T, Li M, Feng WT, Yue RM, Pan C, Huang XB, Kattan E, Zhang Y, Pan LA. Recombinant human brain natriuretic peptide for the recovery stage of septic shock: an interventional study protocol. BMJ Open. 2026 May 24;16(5):e110628. doi: 10.1136/bmjopen-2025-110628. PMID 42192636

Identifiers

NCT: NCT06745206 · 2024-653-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗