Terlipressin in Septic Shock: Effects on Microcirculation

Phase 2

Completed

• Conditions: Septic Shock; Sepsis
• Interventions: Drug: terlipressin bolus administration; Drug: continuous infusion of terlipressin; Drug: Arginine vasopressin

• Registration Number: NCT00995839
• Lead Sponsor: University of Roma La Sapienza

Brief Summary

The present study was conducted as a prospective, randomized study to investigate the effects of vasopressin receptor agonists terlipressin and vasopressin on systemic hemodynamics and microcirculation in patients with catecholamine-dependent septic shock.

Detailed Description

60 septic shock patients requiring norepinephrine to maintain mean arterial pressure between 65 and 75 mmHg despite adequate volume resuscitation will be enrolled in the study. After an initial hemodynamic resuscitation aimed at achieve a mean arterial pressure between 65 and 75 mmHg and normovolemia, patients will be randomly allocated to be treated with either a) intravenous administration of terlipressin 1 µg∙kg-1∙h-1 for 6 hrs, b) intravenous administration of arginine vasopressin 0.04 UI∙min-1 for 6 hrs, c) intravenous administration of terlipressin bolus dose of 0.5 mg (each n = 20). In all groups open label norepinephrine will be additionally administered to maintain a mean arterial pressure (MAP) between 65 and 75 mmHg, if necessary. Data from right heart catheterization and sublingual microvascular network will be obtained just before randomization (baseline) and then after 6 hours in the vasopressin, terlipressin infusion and terlipressin bolus groups.

The sublingual microvascular network will be studied using the sidestream dark field (SDF)imaging. The device will be applied on the lateral side of the tongue, in an area approximately 2-4 cm from the tip of the tongue. Sequences of 10 secs from eight adjacent areas will be recorded on disk using a personal computer. These sequences will be later analyzed by an investigator blinded to the patient's diagnosis and therapy.

Study Timeline

• Study Start: 2008-11
• Status Verified: 2009-10
• Study First Submitted: 2009-10-14
• Study First Submitted QC: 2009-10-14
• Study First Posted: 2009-10-15
• Primary Completion: 2010-02
• Study Completion: 2010-02
• Last Update Submitted: 2010-02-03
• Last Update Posted: 2010-02-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Clinical diagnosis of septic shock
• Vasopressor support to maintain mean arterial pressure (MAP) between 65 and 75 mmHg despite adequate volume resuscitation (pulmonary artery occlusion pressure = 13-18 mmHg and central venous pressure = 8-12 mmHg)

Exclusion Criteria

• Pregnancy
• Age < 18 years
• Present or suspected acute mesenteric ischemia
• Vasospastic diathesis (e.g. Raynaud's syndrome or related diseases)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
terlipressin bolus dose	terlipressin bolus administration	-
continuous terlipressin	continuous infusion of terlipressin	-
vasopressin	Arginine vasopressin	-

Primary Outcome Measures

Name	Time	Method
Systemic hemodynamic and Microcirculatory flow index of small and medium vessels (MFI)	over a period of 6 hrs from the time of randomization
Oxygen transport variables	over a period of 6 from the time of randomization

Secondary Outcome Measures

Name	Time	Method
Acid-base homeostasis	over a period of 6 hrs from the time of randomization
Functional capillary density (mm/mm2) (FCD)	over a period of 6 hrs from the time of randomization
De Backer score	over a period of 6 hrs from the time of randomization
Perfused Vessel Density (PVD) (mm/mm2)	over a period of 6 hrs from the time of randomization
Proportion of Perfused vessels (%) (PPV)	over a period of 6 hrs from the time of randomization

Trial Locations

Locations (1)

Departement of Anesthesiology and Intensive Care; 🇮🇹 Rome, I, Italy