Clinical trial NCT06745206: 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: A Pilot Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Sepsis-induced Cardiomyopathy
Lead sponsor: Sichuan Provincial People's Hospital
Sponsor class: OTHER
First posted: 2024-12-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Sepsis-3 criteria met with Sequential Organ Failure Assessment (SOFA) score increase ≥2 points due to suspected/documented infection.
2. Hypotension persisting after initial fluid resuscitation with concurrent hyperlactatemia at shock diagnosis.
3. Hemodynamic stability achieved after adequate initial resuscitation and individualized hemodynamic optimization.
4. Controlled infection source with improving temperature, white blood cell (WBC) count, and procalcitonin.
5. 48-hour trend of decreasing vasopressor requirements and transition to negative fluid balance.
6. Ongoing pulse index continuous cardiac output (PiCCO) hemodynamic monitoring and sinus rhythm.
7. 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 mmHg8.
8. Adequate perfusion with warm extremities, and capillary refill time (CRT) \<3 seconds9.
9. Signs of cardiac dysfunction: BNP\>20010 or NT-proBNP \>900 pg/ml6 or reduced ejection fraction (LVEF \< 50%).
10. No bonus dose of diuretics has been used in the past 6 hour.

Exclusion Criteria:

1. Age \<18 years.
2. Pregnancy or lactation.
3. Arrhythmia.
4. Persistent dependence on moderate-dose vasopressors (norepinephrine equivalent 0.1-0.3 μg/kg/min) to maintain systolic blood pressure (SBP) \<90 and mean arterial pressure (MAP) ≥65 mmHg.
5. 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.
6. Inadequate ultrasound window preventing acquisition of diagnostic-quality images.
7. Altered mental status impeding patient cooperation.
8. Trauma or neurological diseases (including intracerebral hemorrhage and cerebral infarction).
9. Pre-existing severe heart failure (New York Heart Association \[NYHA\] class III-IV) or acute myocardial infarction within the past 30 days.
10. Concurrent enrollment in interventional trials that could confound study outcomes.
11. Inability or unwillingness to provide informed consent.

Primary outcomes:
measure: The pressure gradient of venous return
timeFrame: 30 minutes after intervention
Secondary outcomes:
measure: The reduction in tissue perfusion pressure
timeFrame: 30 minutes after intervention
measure: The reduction in CVP
timeFrame: 30 minutes after intervention
measure: The reduction in GEDI
timeFrame: 30 minutes after intervention
measure: The reduction in LVEDV
timeFrame: 30 minutes after intervention
measure: The reduction in RRI
timeFrame: 30 minutes after intervention
Other outcomes:
measure: Safety outcome
timeFrame: 30 minutes after intervention
Locations:
Study officials:
affiliation: Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital
name: Lingai Pan, MD
role: PRINCIPAL_INVESTIGATOR
References: