Terlipressin in Septic Shock: Effects on Microcirculation

Sponsor

University of Roma La Sapienza (Other)

Overall Status

Completed

CT.gov ID

NCT00995839

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Septic Shock Sepsis	Drug: continuous infusion of terlipressin Drug: Arginine vasopressin Drug: terlipressin bolus administration	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Vasopressin Receptor Agonists in Septic Shock: Effects on Microcirculation

Study Start Date :

Nov 1, 2008

Actual Primary Completion Date :

Feb 1, 2010

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: continuous terlipressin	Drug: continuous infusion of terlipressin Intravenous continuous infusion of terlipressin 1 µg•kg-1•h-1 for 6 hrs
Experimental: vasopressin	Drug: Arginine vasopressin Intravenous continuous infusion of arginine vasopressin 0.04 UI•min-1 for 6 hrs
Experimental: terlipressin bolus dose	Drug: terlipressin bolus administration intravenous terlipressin bolus administration at the dose of 0.5 mg

Arm

Intervention/Treatment

Experimental: continuous terlipressin

Drug: continuous infusion of terlipressin

Intravenous continuous infusion of terlipressin 1 µg•kg-1•h-1 for 6 hrs

Experimental: vasopressin

Drug: Arginine vasopressin

Intravenous continuous infusion of arginine vasopressin 0.04 UI•min-1 for 6 hrs

Experimental: terlipressin bolus dose

Drug: terlipressin bolus administration

intravenous terlipressin bolus administration at the dose of 0.5 mg

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)