Terlipressin in Septic Shock: Effects on Microcirculation

This study has been completed.
Sponsor:
Information provided by:
University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT00995839
First received: October 14, 2009
Last updated: February 3, 2010
Last verified: October 2009
  Purpose

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 Intervention Phase
Septic Shock
Sepsis
Drug: continuous infusion of terlipressin
Drug: Arginine vasopressin
Drug: terlipressin bolus administration
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Vasopressin Receptor Agonists in Septic Shock: Effects on Microcirculation

Resource links provided by NLM:


Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:
  • Systemic hemodynamic and Microcirculatory flow index of small and medium vessels (MFI) [ Time Frame: over a period of 6 hrs from the time of randomization ] [ Designated as safety issue: No ]
  • Oxygen transport variables [ Time Frame: over a period of 6 from the time of randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acid-base homeostasis [ Time Frame: over a period of 6 hrs from the time of randomization ] [ Designated as safety issue: No ]
  • Functional capillary density (mm/mm2) (FCD) [ Time Frame: over a period of 6 hrs from the time of randomization ] [ Designated as safety issue: No ]
  • De Backer score [ Time Frame: over a period of 6 hrs from the time of randomization ] [ Designated as safety issue: No ]
  • Perfused Vessel Density (PVD) (mm/mm2) [ Time Frame: over a period of 6 hrs from the time of randomization ] [ Designated as safety issue: No ]
  • Proportion of Perfused vessels (%) (PPV) [ Time Frame: over a period of 6 hrs from the time of randomization ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: November 2008
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00995839

Locations
Italy
Departement of Anesthesiology and Intensive Care
Rome, I, Italy, 00161
Sponsors and Collaborators
University of Roma La Sapienza
Investigators
Principal Investigator: Andrea Morelli, MD University of Rome "La Sapienza", Department of Anesthesiology and Intensive Care
  More Information

No publications provided by University of Roma La Sapienza

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Andrea Morelli, University of Rome "La Sapienza"
ClinicalTrials.gov Identifier: NCT00995839     History of Changes
Other Study ID Numbers: 1065
Study First Received: October 14, 2009
Last Updated: February 3, 2010
Health Authority: Italy: Ethics Committee

Keywords provided by University of Roma La Sapienza:
terlipressin
vasopressin
sepsis
septic shock
norepinephrine

Additional relevant MeSH terms:
Shock
Shock, Septic
Infection
Inflammation
Pathologic Processes
Sepsis
Systemic Inflammatory Response Syndrome
Arginine Vasopressin
Lypressin
Terlipressin
Vasopressins
Antidiuretic Agents
Antihypertensive Agents
Cardiovascular Agents
Coagulants
Hematologic Agents
Hemostatics
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on October 23, 2014