Administration of Human Protein C Concentrates in Patients With Sepsis and Septic Shock.

Administration of Human Protein C Concentrates in Patients With Sepsis and Septic Shock: Effects on Microcirculation and Organ Function.

The purpose of this study is to investigate the effects on systemic hemodynamics, microcirculation and organ function of human Protein C concentrate in patients with sepsis and septic shock.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Drug: Human protein C concentrate; Drug: Activated protein C; Drug: Placebo comparator

Detailed Description

Sixty septic patients with plasma protein C activity < 60 % will be enrolled in the study. Patients will be randomly allocated to be treated with either a) a continuous infusion of human Protein C concentrate at 3 UI/Kg/hr for 72 hours to reach plasma protein C activity between 70 and 120 % b)to a continuous infusion of activated protein C at 24 micrograms/Kg/hr for 96 hours, c) a standard teatment(control; each n = 20). In all groups, norepinephrine will be titrated to achieve a mean arterial pressure (MAP) between 65 and 75 mmHg. Data from right heart catheterization, from microcirculation (SDF imaging) and from organ function as well as norepinephrine requirements will be obtained at baseline and after 24, 48, 72 hours.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00161
    • Departement of Anesthesiology and Intensive Care of the University of Rome La Sapienza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Severe sepsis or septic shock with plasma activity of protein C < 60 %

Exclusion Criteria:

• Pregnancy
• Risk of Bleeding
• Hemorragia
• age < 18

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Standard treatment	Drug: Placebo comparator; Standard treatment
Experimental: Human protein C concentrate	Drug: Human protein C concentrate; Continuous infusion of human protein C concentrate at the dose of 3 UI/Kg/Hr to reach a protein C plasma activity of 70-120%
Active Comparator: activated protein C; Continuous infusion of Activated Protein C	Drug: Activated protein C; Continuous infusion of activated protein C at the dose of 24 micrograms/Kg/Hr for 96 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
plasma protein C activity	over a period of 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sublingual microcirculatory blood flow	Systemic hemodynamics,sublingual microcirculatory blood flow, organ function, citokynes.	over a period of 72 hours

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: August 5, 2011
• First Submitted That Met QC Criteria: August 5, 2011
• First Posted (Estimate): August 8, 2011

Study Record Updates

• Last Update Posted (Estimate): December 2, 2015
• Last Update Submitted That Met QC Criteria: December 1, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Septic Shock; Sepsis; Microcirculation; Activated protein C; Human Protein C
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Shock, Septic; Shock; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Protein C; Drotrecogin alfa activated
• Other Study ID Numbers: 2112