Clinical trial NCT00995839: Terlipressin in Septic Shock: Effects on Microcirculation
Official title: Vasopressin Receptor Agonists in Septic Shock: Effects on Microcirculation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Septic Shock
Sepsis
Keywords: terlipressin
vasopressin
sepsis
septic shock
norepinephrine
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2009-10-15
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Systemic hemodynamic and Microcirculatory flow index of small and medium vessels (MFI)
timeFrame: over a period of 6 hrs from the time of randomization
measure: Oxygen transport variables
timeFrame: over a period of 6 from the time of randomization
Secondary outcomes:
measure: Acid-base homeostasis
timeFrame: over a period of 6 hrs from the time of randomization
measure: Functional capillary density (mm/mm2) (FCD)
timeFrame: over a period of 6 hrs from the time of randomization
measure: De Backer score
timeFrame: over a period of 6 hrs from the time of randomization
measure: Perfused Vessel Density (PVD) (mm/mm2)
timeFrame: over a period of 6 hrs from the time of randomization
measure: Proportion of Perfused vessels (%) (PPV)
timeFrame: over a period of 6 hrs from the time of randomization
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Departement of Anesthesiology and Intensive Care
state: I
Study officials:
affiliation: University of Rome "La Sapienza", Department of Anesthesiology and Intensive Care
name: Andrea Morelli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morelli A, Donati A, Ertmer C, Rehberg S, Kampmeier T, Orecchioni A, Di Russo A, D'Egidio A, Landoni G, Lombrano MR, Botticelli L, Valentini A, Zangrillo A, Pietropaoli P, Westphal M. Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock. Crit Care. 2011;15(5):R217. doi: 10.1186/cc10453. Epub 2011 Sep 19.