Papaverine and Sublingual Microcirculation in Septic Shock

NCT07657741 | Not Yet Recruiting

• 1 other identifier: 2026-ICU08
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Sublingual Microcirculation; Septic Shock; Microcirculatory Dysfunction; Hemodynamic Instability

Keywords

Septic shock; Papaverine; Sublingual microcirculation; Microcirculatory dysfunction; Vascular waterfall phenomenon; Critical closing pressure; Perfused vessel density; Microvascular flow index; Proportion of perfused vessels; Pilot physiological study

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Sublingual Microvascular Flow Index

  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

  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

Secondary Outcomes (12)

• Change From Baseline in Perfused Vessel Density

  Baseline, 3 hours, and 6 hours after initiation of papaverine

• Change From Baseline in Proportion of Perfused Vessels

  Baseline, 3 hours, and 6 hours after initiation of papaverine

• Change From Baseline in Microcirculatory Heterogeneity Index

  Baseline, 3 hours, and 6 hours after initiation of papaverine

• Change From Baseline in Estimated Critical Closing Pressure

  Baseline, 3 hours, and 6 hours after initiation of papaverine

• Change From Baseline in Estimated Mean Systemic Filling Pressure

  Baseline, 3 hours, and 6 hours after initiation of papaverine

Study Arms (1)

Papaverine Group

EXPERIMENTAL

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.

Drug: Papaverine

Interventions

Papaverine DRUG

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.

Papaverine Group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Wannan Medical College: lead
• The First Affiliated Hospital of Bengbu Medical University: collaborator

Study Sites (2)

The First Affiliated Hospital of Bengbu Medical University

Bengbu, Anhui, 233000, China

Location

The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College)

Wuhu, Anhui, 241000, China

Location

MeSH Terms

Conditions

Shock, Septic

Interventions

Papaverine

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Opiate Alkaloids; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

qiancheng xu, PhD

CONTACT

+86-18297529106; qianchengxu@wnmc.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: All enrolled patients will receive intravenous papaverine in addition to standard care for septic shock. Physiological measurements will be performed before and after papaverine administration.

Study Record Dates

• First Submitted: June 14, 2026
• First Posted: June 18, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: June 18, 2026

Record last verified: 2026-06

Locations

CN (2)