Questa pagina è stata tradotta automaticamente e l'accuratezza della traduzione non è garantita. Si prega di fare riferimento al Versione inglese per un testo di partenza.

Papaverine and Sublingual Microcirculation in Septic Shock

14 giugno 2026 aggiornato da: Qiancheng Xu, First Affiliated Hospital of Wannan Medical College

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

This is a prospective, multicenter, single-arm, open-label, pilot physiological study designed to evaluate the effects of intravenous papaverine on sublingual microcirculation and the vascular waterfall phenomenon in adult patients with septic shock.

Eligible patients will have septic shock according to Sepsis-3 criteria, require norepinephrine support after adequate fluid resuscitation, and have PiCCO-based hemodynamic monitoring available before papaverine administration. Papaverine will be administered as an intravenous infusion of 30 mg over 10 minutes, followed by a continuous infusion of 2-5 mg/hour. Sublingual microcirculatory variables, vascular-waterfall-related indices, PiCCO-derived hemodynamic variables, macrocirculatory parameters, tissue perfusion variables, vasopressor dose, and safety outcomes will be assessed before and after papaverine administration.

The study aims to explore whether papaverine can improve microvascular perfusion and reduce microcirculatory flow impairment in septic shock, and to provide preliminary physiological and safety data for future controlled trials.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Septic shock is characterized by profound circulatory and metabolic abnormalities, including systemic vasodilation, endothelial dysfunction, altered vascular tone, impaired tissue perfusion, and microcirculatory heterogeneity. Sublingual microcirculatory alterations, such as reduced perfused vessel density, decreased proportion of perfused vessels, impaired microvascular flow index, and increased flow heterogeneity, have been associated with organ dysfunction and adverse outcomes in septic shock.

In addition to global hemodynamic derangements, septic shock may involve abnormal regulation of the effective downstream pressure of the circulation. The vascular waterfall phenomenon refers to a physiological condition in which blood flow is limited by a critical closing pressure or effective downstream pressure that exceeds venous pressure, resulting in impaired flow despite an apparently adequate macrocirculatory pressure gradient. This phenomenon may contribute to the dissociation between macrocirculation and microcirculation observed in septic shock.

Papaverine is a non-selective phosphodiesterase inhibitor and direct smooth muscle relaxant with vasodilatory properties. It has been used clinically to relieve vascular spasm and improve regional blood flow in different vascular beds. By reducing vascular smooth muscle tone, papaverine may improve microvascular perfusion and influence vascular-waterfall-related physiology. However, its effects on sublingual microcirculation and vascular waterfall phenomenon in septic shock remain unclear.

In this study, patients with septic shock will undergo baseline measurements before papaverine initiation. Papaverine will then be administered intravenously at 30 mg over 10 minutes, followed by continuous infusion at 2-5 mg/hour. The infusion rate may be adjusted according to mean arterial pressure, heart rate, vasopressor requirement, PiCCO-derived hemodynamic variables, and adverse events. Sublingual microcirculation will be assessed using handheld vital microscopy. PiCCO-derived hemodynamics, arterial pressure, central venous pressure, lactate, urine output, vasopressor dose, and safety variables will be recorded at predefined time points.

This pilot physiological study is intended to generate preliminary data regarding the microcirculatory effects, vascular-waterfall-related effects, feasibility, and safety of papaverine in patients with septic shock.

Tipo di studio

Interventistico

Iscrizione (Stimato)

20

Fase

  • Non applicabile

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Cina
    • Anhui
      • Bengbu, Anhui, Cina, 233000
        • The First Affiliated Hospital of Bengbu Medical University
        • Contatto:
      • Wuhu, Anhui, Cina, 241000
        • The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College)
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  • Age 18-85 years.
  • Septic shock according to Sepsis-3 criteria, defined as suspected or documented infection requiring vasopressors 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 in the ICU.
  • Receiving continuous norepinephrine infusion at enrollment.
  • Receiving invasive mechanical ventilation at enrollment, allowing assessment of vascular waterfall-related hemodynamic variables.
  • PiCCO-based hemodynamic monitoring, invasive arterial pressure monitoring, and central venous access available before papaverine administration.
  • 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 primarily caused by non-septic etiologies, including cardiogenic, hypovolemic, obstructive, hemorrhagic, or anaphylactic shock.
  • Expected death or planned withdrawal of life-sustaining treatment within 24 hours.
  • Known allergy or hypersensitivity to papaverine.
  • Severe hemodynamic instability judged unsuitable for papaverine by the treating physician, including refractory hypotension or rapidly escalating vasopressor requirement.
  • Clinically significant arrhythmia, high-grade atrioventricular block, acute coronary syndrome, or active myocardial ischemia before enrollment.
  • Severe hepatic dysfunction judged by the investigator to substantially increase the risk of papaverine-related adverse effects.
  • Conditions preventing reliable sublingual microcirculatory assessment, including major oral or sublingual lesions, active oral bleeding, inability to access the sublingual area, or poor baseline image quality.
  • Pregnancy or lactation.
  • Participation in another interventional clinical trial that may affect study outcomes or safety.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Scienza basilare
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Papaverine Group
Adult patients with septic shock receiving norepinephrine support and PiCCO-based hemodynamic monitoring will receive intravenous papaverine. Papaverine will be administered as 30 mg over 10 minutes, followed by continuous infusion at 2-5 mg/hour. Sublingual microcirculatory variables, vascular-waterfall-related indices, PiCCO-derived hemodynamics, macrocirculatory parameters, tissue perfusion variables, vasopressor requirement, and safety outcomes will be assessed before and after papaverine administration.
Droga: Papaverine
Papaverine will be administered intravenously as 30 mg infused over 10 minutes, followed by continuous infusion at 2-5 mg/hour. The maintenance infusion rate may be adjusted according to the patient's hemodynamic status, mean arterial pressure, heart rate, vasopressor requirement, PiCCO-derived variables, and adverse events. Dose reduction, temporary interruption, or discontinuation of papaverine is permitted for safety reasons, including clinically significant hypotension, rapidly increasing vasopressor requirement, new-onset or worsening arrhythmia, myocardial ischemia, severe liver function abnormality, or any other clinically significant adverse event judged by the treating physician or investigator.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change From Baseline in Sublingual Microvascular Flow Index
Lasso di tempo: Baseline, 3 hours, and 6 hours after initiation of papaverine
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 each post-papaverine time point.
Baseline, 3 hours, and 6 hours after initiation of papaverine
Change From Baseline in Pcc-Pmsf Gradient
Lasso di tempo: Baseline, 3 hours, and 6 hours after initiation of papaverine
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 each post-papaverine time point.
Baseline, 3 hours, and 6 hours after initiation of papaverine

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change From Baseline in Perfused Vessel Density
Lasso di tempo: Baseline, 3 hours, and 6 hours after initiation of papaverine
Perfused vessel density will be measured from sublingual microcirculatory images. The outcome is the change in PVD from baseline to each post-papaverine time point
Baseline, 3 hours, and 6 hours after initiation of papaverine
Change From Baseline in Proportion of Perfused Vessels
Lasso di tempo: Baseline, 3 hours, and 6 hours after initiation of papaverine
Proportion of perfused vessels will be measured from sublingual microcirculatory images. The outcome is the change in PPV from baseline to each post-papaverine time point
Baseline, 3 hours, and 6 hours after initiation of papaverine
Change From Baseline in Microcirculatory Heterogeneity Index
Lasso di tempo: Baseline, 3 hours, and 6 hours after initiation of papaverine
Microcirculatory heterogeneity index will be calculated from sublingual microcirculatory measurements. The outcome is the change in HI from baseline to each post-papaverine time point.
Baseline, 3 hours, and 6 hours after initiation of papaverine
Change From Baseline in Estimated Critical Closing Pressure
Lasso di tempo: Baseline, 3 hours, and 6 hours after initiation of papaverine
Estimated critical closing pressure will be calculated using predefined hemodynamic methods. The outcome is the change in Pcc from baseline to each post-papaverine time point.
Baseline, 3 hours, and 6 hours after initiation of papaverine
Change From Baseline in Estimated Mean Systemic Filling Pressure
Lasso di tempo: Baseline, 3 hours, and 6 hours after initiation of papaverine
Estimated mean systemic filling pressure will be calculated using predefined hemodynamic methods. The outcome is the change in Pmsf from baseline to each post-papaverine time point
Baseline, 3 hours, and 6 hours after initiation of papaverine
Change From Baseline in Mean Arterial Pressure
Lasso di tempo: Baseline, 3 hours, and 6 hours after initiation of papaverine
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 each post-papaverine time point.
Baseline, 3 hours, and 6 hours after initiation of papaverine
Change From Baseline in Cardiac Index
Lasso di tempo: Baseline, 3 hours, and 6 hours after initiation of papaverine
Cardiac index will be measured using PiCCO-based transpulmonary thermodilution and/or pulse contour analysis. The outcome is the change in cardiac index from baseline to each post-papaverine time point.
Baseline, 3 hours, and 6 hours after initiation of papaverine
Change From Baseline in Norepinephrine Dose
Lasso di tempo: Baseline, 3 hours, and 6 hours after initiation of papaverine
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 each post-papaverine time point.
Baseline, 3 hours, and 6 hours after initiation of papaverine
Change From Baseline in Arterial Lactate
Lasso di tempo: Baseline and 6 hours after initiation of papaverine
Arterial lactate concentration will be measured according to routine clinical practice. The outcome is the change in lactate from baseline to 6 hours after initiation of papaverine.
Baseline and 6 hours after initiation of papaverine
28-Day Mortality
Lasso di tempo: 28 days after enrollment
All-cause mortality within 28 days after enrollment.
28 days after enrollment
Ventilator-Free Days at Day 28
Lasso di tempo: 28 days after enrollment.
Number of days alive and free from invasive mechanical ventilation within 28 days after enrollment
28 days after enrollment.
Incidence of Prespecified Adverse Events
Lasso di tempo: From initiation of papaverine to 6 hours after initiation
Prespecified adverse events include clinically significant hypotension, new-onset or worsening arrhythmia, suspected myocardial ischemia, reduction in cardiac index requiring treatment modification, escalation of vasopressor or inotropic support, interruption or discontinuation of papaverine for safety reasons, cardiac arrest, or other clinically significant events during the observation period
From initiation of papaverine to 6 hours after initiation

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

First Affiliated Hospital of Wannan Medical College

Collaboratori

The First Affiliated Hospital of Bengbu Medical University

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 agosto 2026

Completamento primario (Stimato)

1 dicembre 2027

Completamento dello studio (Stimato)

30 dicembre 2027

Date di iscrizione allo studio

Primo inviato

14 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

14 giugno 2026

Primo Inserito (Effettivo)

18 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

18 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

14 giugno 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 2026-ICU08

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

INDECISO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su Shock settico

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in Nigeria

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

Sottoscrivi