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Comparison of Angiotensin II to Standard Dose Vasopressors on Change in Arterial Elastance (Ang2)

28 de abril de 2026 atualizado por: Siddharth Dugar, The Cleveland Clinic

Comparison of Angiotensin II to Standard Dose Vasopressors on Change in Arterial Elastance in Cirrhotic Patients With Vasodilatory Shock: A Prospective, Randomized Controlled Trial

A study to see whether a medication called Angiotensin II works better than the routinely used medication to raise blood pressure in people with liver disease who are experiencing a serious drop in blood pressure.

The investigators want to find out if Angiotensin II can help the heart and blood vessels work together more effectively than standard treatments.

Visão geral do estudo

Status

Ativo, não recrutando

Condições

Intervenção / Tratamento

Descrição detalhada

Sepsis and septic shock remain associated with significant mortality, especially in cirrhotic where the mortality with septic shock exceeds 70%. Cirrhotic cardiomyopathy is a well-recognized consequence of advanced liver dysfunction and is associated with a hyperdynamic circulatory state due to vasoplegia in this population. Our group has shown septic patients with cirrhosis had higher LV systolic function as assessed by Left ventricle Ejection fraction (LVEF %), stroke volume and cardiac output with a significantly higher percentage of patients with hyperdynamic state (LVEF > 70%) than those without cirrhosis.

The investigators measured arterial elastance and ventricular elastance using echocardiography and found cirrhotic patient to have significantly lower arterial elastance with higher ventricular elastance. AII (Angiotensin II) exert its effect after the hydrolysis of Ang-1 by angiotensin converting enzyme (ACE) and is the principal product of the renin-angiotensin-aldosterone system. Advance cirrhosis is associated with reduction in Ang II levels accompanied by an increased Ang-(1-7)/Ang II ratio in the splanchnic circulation may be, at least in part, responsible for changes in vascular splanchnic tone. In addition, the relative decrease in Ang II compared to Ang (1-7), the vasodilator component of RAS causes hyperdynamic circulation from lower SVR in cirrhotic. This study also showed that with progression of liver disease leads to continual splanchnic vasodilation from higher Ang (1-7)/Ang II ratio. In advance stages this resultant hyperdynamic circulation is still insufficient to compensate for the effective arterial hypovolemia. Similar finding was observed in our large study, where the VAC was significantly lower in cirrhotic with sepsis shock despite elevation in LV elastance compared to non-cirrhotic with septic shock.

Angiotensin II, a naturally occurring octapeptide hormone increases blood pressure through various mechanisms, including vasoconstriction of peripheral vessels, potentiation of antidiuretic hormone (ADH) and adrenocorticotropin hormone (ACTH) release, and direct actions on postganglionic sympathetic fibers. The external Ang II administration will be able to reverse the altered Ang (I-7)/Ang II ratio in systemic circulation reversing vasodilation. The investigators hypothesize that external administration of Ang II will cause a higher increase in SVR in cirrhotic with septic shock compared to Standard of Care (SOC) by decreasing arterial elastance restoring non-invasive arterial ventricular coupling.

Tipo de estudo

Intervencional

Inscrição (Real)

30

Estágio

  • Fase inicial 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Estados Unidos
    • Ohio
      • Cleveland, Ohio, Estados Unidos, 44195
        • The Cleveland Clinic

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

Inclusion Criteria:

  • Age ≥ 18 years at the time of enrollment
  • Septic shock as defined by Sepsis-3 criteria (highly suspected or confirmed infection, requiring norepinephrine to maintain a MAP ≥ 65 mmHg, and serum lactate > 2 mmol/L after adequate fluid resuscitation) within a 48 hour window prior to enrollment
  • Confirmed cirrhotic patient (Radiological/Biopsy/Physician confirmed)
  • Preserved cardiac function as assessed using point-of-care ultrasonography or a non-invasive hemodynamic monitoring device with either LVOT VTI > 18 cm or stroke volume > 50 ml Within 48 hours of onset of shock.
  • Standard of care vasopressors are at a norepinephrine equivalent of 15 mcg/min

Exclusion Criteria:

  • Declined consent.
  • Pregnancy
  • CKD-Stage IV/V
  • ESRD on long-term hemodialysis
  • On Dialysis or planned dialysis to be initiated within 24 hours of study of enrollment.
  • Clinically determined to have primarily hepatorenal syndrome.
  • On other vasoactive medication (phenylephrine, Terlipressin, epinephrine, dobutamine, dopamine)
  • Hemorrhagic, obstructive, or hypovolemic shock is not the primary cause of shock based on clinical judgement.
  • DNR
  • Patients declared Brain dead.
  • Anticipated death within 48 hours of enrollment
  • Echocardiographic windows not available
  • Acute mesenteric Ischemia
  • Active gastrointestinal bleeding
  • Active cardiac ischemic event defined as NSTEMi, STEMI
  • Acute DVT/Pulmonary embolism/Portal vein thrombosis
  • > 48 h since initiation of vasopressor agent
  • Cardiac function assessment show LVOT VTI < 18 cm or stroke volume < 50 ml/min
  • Norepinephrine equivalent dose > 50mcg/min

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Comparador Ativo: Angiotensin II
Angiotensin II will be continued for 24 hours and then discontinued, and SOC vasopressors resumed according to institutional practices.
Medicamento: Giapreza
2.5 mg/mL
Outros nomes:
  • Angiotension II
Sem intervenção: Standard of Care
Fixed-dose vasopressin and standard of care vasopressors increased as per institutional guidelines according to MAP targets.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Change in arterial elastance
Prazo: 6 hours
Change in arterial elastance will be measure by echocardiography at baseline, 6 hours and 24 hours. Dynamic arterial elastance will be calculated as the ratio between pulse pressure variation and stroke volume variation obtained from arterial line waveform.
6 hours
Change in arterial elastance
Prazo: 24 hours
Change in arterial elastance will be measure by echocardiography at baseline, 6 hours and 24 hours. Dynamic arterial elastance will be calculated as the ratio between pulse pressure variation and stroke volume variation obtained from arterial line waveform.
24 hours

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Change in arterial ventricular coupling
Prazo: 6 hours
Change in arterial ventricular coupling will be measured by echocardiogram at baseline, 6 hours and 24 hours. The ventricular-arterial coupling will be assessed using previously validated method where Left ventricular end-systolic elastance will be calculated by a modified single-beat method employing systolic and diastolic pressure from the arterial line, echo-Doppler stroke volume (SV), echo-derived ejection fraction (EF) and an estimated normalized ventricular elastance at arterial end-diastole (E(Nd)): E(es(sb)) = [P(d) - (E(Nd(est)) x P(s) x 0.9)[/(E(Nd(est)) x SV).
6 hours
Change in arterial ventricular coupling
Prazo: 24 hours
Change in arterial ventricular coupling will be measured by echocardiogram at baseline, 6 hours and 24 hours. The ventricular-arterial coupling will be assessed using previously validated method where Left ventricular end-systolic elastance will be calculated by a modified single-beat method employing systolic and diastolic pressure from the arterial line, echo-Doppler stroke volume (SV), echo-derived ejection fraction (EF) and an estimated normalized ventricular elastance at arterial end-diastole (E(Nd)): E(es(sb)) = [P(d) - (E(Nd(est)) x P(s) x 0.9)[/(E(Nd(est)) x SV).
24 hours
Change in norepinephrine equivalent dose
Prazo: 6 hours
The change in norepinephrine equivalent dose at (6 hours and 24 hours) using the following formula6 Norepinephrine dose (µg/kg/min) + epinephrine dose (µg/kg/min) + 1/150 × dopamine dose (µg/kg/min) + 1/10 × phenylephrine dose (µg/kg/min) + 2.5 × vasopressin dose (U/min)
6 hours
Change in norepinephrine equivalent dose
Prazo: 24 hours
The change in norepinephrine equivalent dose at (6 hours and 24 hours) using the following formula6 Norepinephrine dose (µg/kg/min) + epinephrine dose (µg/kg/min) + 1/150 × dopamine dose (µg/kg/min) + 1/10 × phenylephrine dose (µg/kg/min) + 2.5 × vasopressin dose (U/min)
24 hours
Change in renal perfusion index
Prazo: 6 hours

Improvement in renal perfusion index (Renal Resistive index) at (6 hours and 24 hours).

The Doppler-based renal restrictive index (RI) will be used for measurement using spectral Doppler at the arcuate arteries or interlobar arteries. The formula for calculating the RI is: RI = (Peak Systolic Velocity - End Diastolic Velocity) / Peak Systolic Velocity. The normal range for the RI is 0.50 to 0.70, and elevated values are associated with poorer prognosis in various renal disorders and renal transplant outcomes.
6 hours
Change in renal perfusion index
Prazo: 24 hours

Improvement in renal perfusion index (Renal Resistive index) at (6 hours and 24 hours).

The Doppler-based renal restrictive index (RI) will be used for measurement using spectral Doppler at the arcuate arteries or interlobar arteries. The formula for calculating the RI is: RI = (Peak Systolic Velocity - End Diastolic Velocity) / Peak Systolic Velocity. The normal range for the RI is 0.50 to 0.70, and elevated values are associated with poorer prognosis in various renal disorders and renal transplant outcomes.
24 hours
Evaluation of 28 day renal replacement therapy free survival
Prazo: 28 days after hospital discharge
The number of days alive free of renal-replacement therapy at 28 days
28 days after hospital discharge
Change in Renin levels
Prazo: 24 hours

A blood sample will be obtained at two time points. The first sample will be obtained when the participant is randomized but before infusion in initiated. The second sample will be obtained at 24 hours after the initiation of the drug.

Plasma Renin Activity (PRA) is measured in ng/mL/h.
24 hours
Change in Angiotension II levels
Prazo: 24 hours

A blood sample will be obtained at two time points. The first sample will be obtained when the participant is randomized but before infusion in initiated. The second sample will be obtained at 24 hours after the initiation of the drug.

Angiotensin II will be expressed in ng/dL.
24 hours
Change in Microcirculation
Prazo: 6 hours
Tissue oxygen saturation (StO₂) will be measured using near-infrared spectroscopy (NIRS) at the thenar eminence. Microvascular reactivity will be assessed using a vascular occlusion test (VOT). Dynamic variables derived from the VOT will include baseline StO₂, minimum StO₂ during occlusion, and reperfusion slope.
6 hours
Change in Microcirculation
Prazo: 24 hours
Tissue oxygen saturation (StO₂) will be measured using near-infrared spectroscopy (NIRS) at the thenar eminence. Microvascular reactivity will be assessed using a vascular occlusion test (VOT). Dynamic variables derived from the VOT will include baseline StO₂, minimum StO₂ during occlusion, and reperfusion slope.
24 hours

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

The Cleveland Clinic

Colaboradores

Innoviva Specialty Therapeutics

Investigadores

  • Investigador principal: Siddharth Dugar, M.D., The Cleveland Clinic

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

15 de novembro de 2024

Conclusão Primária (Estimado)

1 de janeiro de 2028

Conclusão do estudo (Estimado)

1 de janeiro de 2028

Datas de inscrição no estudo

Enviado pela primeira vez

19 de fevereiro de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

28 de abril de 2026

Primeira postagem (Real)

5 de maio de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

5 de maio de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

28 de abril de 2026

Última verificação

1 de fevereiro de 2026

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • 24-913

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano IPD

After the study is completed, de-identified data and study documents may be shared on ClinicalTrials.gov in accordance with institutional policies and regulatory requirements.

Prazo de Compartilhamento de IPD

Starting in January 2029.

Critérios de acesso de compartilhamento IPD

Researchers can access the information on clinicaltrials.gov.

Tipo de informação de suporte de compartilhamento de IPD

  • PROTOCOLO DE ESTUDO
  • SEIVA
  • CIF
  • ANALYTIC_CODE
  • CSR

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

produto fabricado e exportado dos EUA

Sim

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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