Terlipressin in Septic Shock: Effects on Microcirculation

Sepsis Clinical Trial

Official title:

Vasopressin Receptor Agonists in Septic Shock: Effects on Microcirculation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00995839
• Other study ID #: 1065
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 14, 2009
• Last updated: February 3, 2010
• Start date: November 2008
• Est. completion date: February 2010

Study information

• Verified date: October 2009
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Shock
• Shock, Septic

Intervention

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

Locations

Country	Name	City	State
Italy	Departement of Anesthesiology and Intensive Care	Rome	I

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Systemic hemodynamic and Microcirculatory flow index of small and medium vessels (MFI)		over a period of 6 hrs from the time of randomization	No
Primary	Oxygen transport variables		over a period of 6 from the time of randomization	No
Secondary	Acid-base homeostasis		over a period of 6 hrs from the time of randomization	No
Secondary	Functional capillary density (mm/mm2) (FCD)		over a period of 6 hrs from the time of randomization	No
Secondary	De Backer score		over a period of 6 hrs from the time of randomization	No
Secondary	Perfused Vessel Density (PVD) (mm/mm2)		over a period of 6 hrs from the time of randomization	No
Secondary	Proportion of Perfused vessels (%) (PPV)		over a period of 6 hrs from the time of randomization	No