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Papaverine and Sublingual Microcirculation in Septic Shock

2026년 6월 14일 업데이트: 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.

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

20

단계

  • 해당 없음

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 장소

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

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 기초 과학
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
의약품: 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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Change From Baseline in Sublingual Microvascular Flow Index
기간: 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
기간: 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

2차 결과 측정

결과 측정
측정값 설명
기간
Change From Baseline in Perfused Vessel Density
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 28 days after enrollment
All-cause mortality within 28 days after enrollment.
28 days after enrollment
Ventilator-Free Days at Day 28
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

First Affiliated Hospital of Wannan Medical College

협력자

The First Affiliated Hospital of Bengbu Medical University

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 8월 1일

기본 완료 (추정된)

2027년 12월 1일

연구 완료 (추정된)

2027년 12월 30일

연구 등록 날짜

최초 제출

2026년 6월 14일

QC 기준을 충족하는 최초 제출

2026년 6월 14일

처음 게시됨 (실제)

2026년 6월 18일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 6월 18일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 6월 14일

마지막으로 확인됨

2026년 6월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 2026-ICU08

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

미정

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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