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Papaverine and Sublingual Microcirculation in Septic Shock

14 juin 2026 mis à jour par: 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.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

20

Phase

  • N'est pas applicable

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Science basique
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: 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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Change From Baseline in Sublingual Microvascular Flow Index
Délai: 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
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Change From Baseline in Perfused Vessel Density
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 28 days after enrollment
All-cause mortality within 28 days after enrollment.
28 days after enrollment
Ventilator-Free Days at Day 28
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

First Affiliated Hospital of Wannan Medical College

Collaborateurs

The First Affiliated Hospital of Bengbu Medical University

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 août 2026

Achèvement primaire (Estimé)

1 décembre 2027

Achèvement de l'étude (Estimé)

30 décembre 2027

Dates d'inscription aux études

Première soumission

14 juin 2026

Première soumission répondant aux critères de contrôle qualité

14 juin 2026

Première publication (Réel)

18 juin 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

18 juin 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

14 juin 2026

Dernière vérification

1 juin 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 2026-ICU08

Plan pour les données individuelles des participants (IPD)

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INDÉCIS

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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