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Effects of Anisodamine on Sublingual Microcirculation and Vascular Waterfall Phenomenon in Patients With Septic Shock (ANISO-MICRO)

14 juni 2026 bijgewerkt door: Qiancheng Xu, First Affiliated Hospital of Wannan Medical College

Effects of Anisodamine on Sublingual Microcirculation and Vascular Waterfall Phenomenon in Patients With Septic Shock: A Prospective, Multicenter, Single-arm, Open-label, Pilot Physiological Study

This prospective, multicenter, single-arm, open-label interventional pilot study aims to evaluate the short-term physiological effects of intravenous anisodamine on sublingual microcirculation and vascular-waterfall parameters in adult patients with septic shock.

Eligible patients will have septic shock according to Sepsis-3 criteria, will require norepinephrine support after adequate fluid resuscitation, and will be receiving invasive mechanical ventilation and PiCCO-based hemodynamic monitoring. After baseline assessment, participants will receive intravenous anisodamine according to the study protocol. Anisodamine will be administered as a loading dose of 0.5 mg/kg within 3 minutes, with a minimum dose of 20 mg and a maximum dose of 40 mg, followed by continuous infusion at 0.02-0.1 mg/kg/hour, with a maximum total daily dose of 200 mg.

Sublingual microcirculatory variables, including microvascular flow index, perfused vessel density, proportion of perfused vessels, and heterogeneity index, as well as vascular-waterfall parameters, including estimated critical closing pressure, estimated mean systemic filling pressure, and the Pcc-Pmsf gradient, will be measured at baseline, 3 hours, and 6 hours after initiation of anisodamine. Systemic hemodynamic, perfusion, vasopressor, PiCCO-derived variables, and safety outcomes will also be collected.

The primary objective is to characterize immediate changes in sublingual microcirculation and vascular-waterfall physiology after anisodamine administration and to provide preliminary data for future controlled studies.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Septic shock is characterized by profound circulatory dysfunction involving both the macrocirculation and the microcirculation. Although conventional resuscitation targets such as mean arterial pressure, cardiac output, and serum lactate are widely used, microcirculatory alterations may persist despite apparent stabilization of systemic hemodynamics. Direct evaluation of sublingual microcirculation may therefore provide additional physiological information in patients with septic shock.

Anisodamine is a non-specific muscarinic cholinoceptor antagonist that has been used in China as an adjunctive therapy in septic shock. Previous clinical studies suggest that anisodamine may improve microcirculatory perfusion, reduce lactate levels, and decrease vasopressor requirements in selected patients with septic shock. However, its immediate effects on directly visualized sublingual microcirculation and vascular-waterfall physiology remain insufficiently characterized.

The vascular-waterfall phenomenon refers to the concept that tissue perfusion is influenced not only by arterial and venous pressures but also by the relationship between upstream pressure, critical closing pressure, and mean systemic filling pressure. In septic shock, changes in vascular tone, vasopressor exposure, vascular closing pressure, and stressed blood volume may alter the effective pressure gradient for tissue perfusion. Evaluation of vascular-waterfall variables together with direct sublingual microcirculatory imaging may provide mechanistic insight into the physiological effects of anisodamine beyond conventional macrocirculatory variables.

This is a prospective, multicenter, single-arm, open-label, interventional pilot physiological study conducted in adult intensive care unit patients with septic shock. Patients will be screened after initial hemodynamic optimization. Eligible patients must have septic shock according to Sepsis-3 criteria, ongoing norepinephrine support, invasive mechanical ventilation, and PiCCO-based hemodynamic monitoring before anisodamine initiation. Patients with contraindications to anisodamine, major conditions interfering with sublingual microcirculatory imaging, severe uncontrolled arrhythmia, or expected death or withdrawal of life-sustaining treatment within 24 hours will be excluded.

After informed consent is obtained, baseline measurements will be performed immediately before anisodamine administration. Anisodamine will be given as an intravenous loading dose of 0.5 mg/kg within 3 minutes, with a minimum dose of 20 mg and a maximum dose of 40 mg, followed by continuous intravenous infusion at 0.02-0.1 mg/kg/hour. The total daily dose will not exceed 200 mg. The maintenance dose may be adjusted by the treating physician according to the patient's microcirculatory status, serum lactate level, capillary refill time, hemodynamics, and adverse effects. Dose reduction, temporary interruption, or discontinuation will be permitted for safety reasons, including clinically significant hypotension, tachycardia, new-onset or worsening arrhythmia, prolonged QT interval, myocardial ischemia, mental status changes, urinary retention, ileus, or other clinically significant adverse events.

Study assessments will be performed at baseline, 3 hours, and 6 hours after initiation of anisodamine. Sublingual microcirculatory imaging will be used to assess microvascular flow index, perfused vessel density, proportion of perfused vessels, and microcirculatory heterogeneity index. Vascular-waterfall related variables will include estimated critical closing pressure, estimated mean systemic filling pressure, and the Pcc-Pmsf gradient. Systemic hemodynamic and perfusion variables, including heart rate, mean arterial pressure, cardiac index, norepinephrine dose, arterial lactate, urine output, capillary refill time, and PiCCO-derived variables, will also be recorded.

Approximately 20 patients will be enrolled to assess feasibility and generate preliminary estimates of physiological changes after anisodamine administration. The main analyses will describe changes from baseline in sublingual microcirculatory and vascular-waterfall parameters over the 6-hour observation period. Safety events, especially tachycardia and arrhythmias, will be summarized descriptively to inform the design of subsequent controlled studies.

Studietype

Ingrijpend

Inschrijving (Geschat)

20

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

  • China
    • Anhui
      • Wuhu, Anhui, China, 241000
        • The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College)
        • Contact:

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Inclusion Criteria:

  • Age 18-85 years.
  • Diagnosis of septic shock according to Sepsis-3 criteria, defined as suspected or documented infection with vasopressor requirement to maintain mean arterial pressure ≥65 mmHg and serum lactate >2 mmol/L after adequate fluid resuscitation.
  • Enrollment within 24 hours after diagnosis of septic shock or within 24 hours after ICU admission for septic shock.
  • Receiving invasive mechanical ventilation at the time of enrollment.
  • PiCCO catheter in place and PiCCO-based hemodynamic monitoring available before anisodamine initiation.
  • Continuous norepinephrine infusion at enrollment.
  • Adequate initial fluid resuscitation and hemodynamic optimization as judged by the treating physician, with volume status assessed by dynamic indices, echocardiography, or PiCCO-derived variables.
  • Ability to obtain sublingual microcirculatory images of acceptable quality at baseline.
  • Written informed consent obtained from the patient or legally authorized representative.

Exclusion Criteria:

  • Shock mainly caused by non-septic etiologies, including cardiogenic, hypovolemic, obstructive, hemorrhagic, or anaphylactic shock.
  • Expected death or withdrawal of life-sustaining treatment within 24 hours.
  • Known contraindications to anisodamine or anticholinergic therapy, including glaucoma, acute phase of intracranial hemorrhage, elevated intracranial pressure, untreated bowel obstruction, or prostatic enlargement without urinary catheterization.
  • Known allergy or hypersensitivity to anisodamine or any component of the study drug.
  • Severe or uncontrolled arrhythmia before enrollment, including sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes, uncontrolled supraventricular tachycardia, or atrial fibrillation/flutter with uncontrolled ventricular response.
  • Acute coronary syndrome, clinically significant myocardial ischemia, or cardiac arrest before enrollment during the current ICU stay.
  • Severe cardiac dysfunction judged unsuitable for anisodamine by the treating physician, including severe ventricular dysfunction, cardiogenic shock, or need for high-dose inotropic support.
  • Conditions interfering with sublingual microcirculatory assessment, including major oral or sublingual lesions, active oral bleeding, inability to access the sublingual area, or poor baseline image quality.
  • Immunocompromised status or agranulocytosis, including long-term immunosuppressive therapy, chemotherapy-associated severe neutropenia, or other severe immune suppression judged by the investigator.
  • Pregnancy, planned pregnancy, or lactation.
  • Participation in another interventional clinical trial that may affect study outcomes or safety.
  • Inability to obtain informed consent.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Fundamentele wetenschap
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Anisodamine arm
Adult patients with septic shock receiving invasive mechanical ventilation, norepinephrine support, and PiCCO-based hemodynamic monitoring after initial resuscitation will receive intravenous anisodamine. Sublingual microcirculatory, vascular-waterfall, PiCCO-derived, macrocirculatory, perfusion, and safety variables will be assessed at baseline, 3 hours, and 6 hours after anisodamine initiation.
Geneesmiddel: Anisodamine intravenous infusion

Anisodamine will be administered as an intravenous loading dose of 0.5 mg/kg within 3 minutes, with a minimum dose of 20 mg and a maximum dose of 40 mg, followed by continuous intravenous infusion at 0.02-0.1 mg/kg/hour. The maximum total daily dose will be 200 mg. The maintenance dose may be adjusted according to microcirculatory status, serum lactate level, capillary refill time, mean arterial pressure, heart rate, PiCCO-derived hemodynamic variables, vasopressor requirement, and adverse effects.

Dose reduction, temporary interruption, or discontinuation is permitted for safety reasons, including clinically significant hypotension, excessive tachycardia, new-onset or worsening arrhythmia, prolonged QT interval, suspected myocardial ischemia, mental status changes, urinary retention, ileus, or other clinically significant adverse events. The actual dose, infusion duration, and reasons for dose adjustment or discontinuation will be recorded.

Andere namen:
  • Anisodamine hydrobromide
  • Ani HBr

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change From Baseline in Pcc-Pmsf Gradient
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
The vascular-waterfall pressure gradient will be calculated as the difference between estimated critical closing pressure and estimated mean systemic filling pressure. The outcome is the change in Pcc-Pmsf from baseline to 3 and 6 hours after anisodamine initiation
Baseline, 3 hours, and 6 hours after initiation of anisodamine
Change From Baseline in Sublingual Microvascular Flow Index
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
Microvascular flow index will be assessed using sublingual microcirculatory imaging. Three to five sublingual video fields will be recorded at each time point, and MFI will be calculated according to standard microcirculatory scoring methods. The outcome is the change in MFI from baseline to 3 and 6 hours after anisodamine initiation.
Baseline, 3 hours, and 6 hours after initiation of anisodamine

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change From Baseline in Perfused Vessel Density
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
Perfused vessel density will be measured from sublingual microcirculatory images. The outcome is the change in PVD from baseline to 3 and 6 hours after anisodamine initiation
Baseline, 3 hours, and 6 hours after initiation of anisodamine
Change From Baseline in Proportion of Perfused Vessels
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
Proportion of perfused vessels will be measured from sublingual microcirculatory images. The outcome is the change in PPV from baseline to 3 and 6 hours after anisodamine initiation
Baseline, 3 hours, and 6 hours after initiation of anisodamine
Change From Baseline in Microcirculatory Heterogeneity Index
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
Microcirculatory heterogeneity index will be calculated from sublingual microcirculatory measurements. The outcome is the change in HI from baseline to 3 and 6 hours after anisodamine initiation
Baseline, 3 hours, and 6 hours after initiation of anisodamine
Change From Baseline in Estimated Critical Closing Pressure
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
Estimated critical closing pressure will be calculated using predefined hemodynamic methods based on arterial pressure waveform-derived parameters and PiCCO-based cardiac output measurements. The outcome is the change in Pcc from baseline to 3 and 6 hours after anisodamine initiation.
Baseline, 3 hours, and 6 hours after initiation of anisodamine
Change From Baseline in Estimated Mean Systemic Filling Pressure
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
Estimated mean systemic filling pressure will be calculated using predefined hemodynamic methods based on PiCCO-derived cardiac output and systemic vascular resistance-related variables. The outcome is the change in Pmsf from baseline to 3 and 6 hours after anisodamine initiation
Baseline, 3 hours, and 6 hours after initiation of anisodamine
Change From Baseline in Mean Arterial Pressure
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
Mean arterial pressure will be recorded from invasive arterial monitoring at each study time point. The outcome is the change in MAP from baseline to 3 and 6 hours after anisodamine initiation
Baseline, 3 hours, and 6 hours after initiation of anisodamine
Change From Baseline in Cardiac Index
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
Cardiac index will be measured using PiCCO-based hemodynamic monitoring. The outcome is the change in cardiac index from baseline to 3 and 6 hours after anisodamine initiation
Baseline, 3 hours, and 6 hours after initiation of anisodamine
Change From Baseline in Norepinephrine Dose
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
Norepinephrine dose will be recorded in μg/kg/min at each study time point. The outcome is the change in norepinephrine dose from baseline to 3 and 6 hours after anisodamine initiation
Baseline, 3 hours, and 6 hours after initiation of anisodamine
Change From Baseline in Arterial Lactate
Tijdsspanne: Baseline and 6 hours after initiation of anisodamine
Arterial lactate concentration will be measured according to routine clinical practice. The outcome is the change in lactate from baseline to 6 hours after anisodamine initiation
Baseline and 6 hours after initiation of anisodamine
Change From Baseline in Capillary Refill Time
Tijdsspanne: Baseline, 3 hours, and 6 hours after initiation of anisodamine
Capillary refill time will be assessed according to local clinical practice. The outcome is the change in capillary refill time from baseline to 3 and 6 hours after anisodamine initiation
Baseline, 3 hours, and 6 hours after initiation of anisodamine
Incidence of New-Onset or Worsening Arrhythmia
Tijdsspanne: From initiation of anisodamine to 6 hours after initiation
New-onset or worsening arrhythmia will be recorded during the observation period. Arrhythmias of interest include atrial fibrillation, atrial flutter, supraventricular tachycardia, frequent ventricular premature beats requiring treatment, ventricular tachycardia, ventricular fibrillation, torsade de pointes, or any arrhythmia requiring treatment modification, antiarrhythmic therapy, cardioversion, or discontinuation of anisodamine
From initiation of anisodamine to 6 hours after initiation
Incidence of Prespecified Adverse Events
Tijdsspanne: From initiation of anisodamine to 6 hours after initiation
Prespecified adverse events include clinically significant hypotension, excessive tachycardia, new-onset or worsening arrhythmia, prolonged QT interval, suspected myocardial ischemia, escalation of vasopressor or inotropic support, interruption or discontinuation of anisodamine for safety reasons, mental status changes, urinary retention, ileus, cardiac arrest, or other clinically significant events during the observation period
From initiation of anisodamine to 6 hours after initiation
ICU Length of Stay
Tijdsspanne: From ICU admission to ICU discharge, assessed up to 28 days after enrollment
Number of days from ICU admission to ICU discharge
From ICU admission to ICU discharge, assessed up to 28 days after enrollment
Ventilator-Free Days at Day 28
Tijdsspanne: 28 days after enrollment
Number of days alive and free from invasive mechanical ventilation within 28 days after enrollment.
28 days after enrollment
28-Day Mortality
Tijdsspanne: 28 days after enrollment
All-cause mortality within 28 days after enrollment
28 days after enrollment

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

First Affiliated Hospital of Wannan Medical College

Medewerkers

The First Affiliated Hospital of Bengbu Medical University

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 augustus 2026

Primaire voltooiing (Geschat)

1 december 2027

Studie voltooiing (Geschat)

30 december 2027

Studieregistratiedata

Eerst ingediend

14 juni 2026

Eerst ingediend dat voldeed aan de QC-criteria

14 juni 2026

Eerst geplaatst (Werkelijk)

18 juni 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

18 juni 2026

Laatste update ingediend die voldeed aan QC-criteria

14 juni 2026

Laatst geverifieerd

1 juni 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 2026-ICU06

Plan Individuele Deelnemersgegevens (IPD)

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Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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