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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Sepsis, Septic Shock

Intervention / Treatment
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* Drug: Human protein C concentrate
* Drug: Activated protein C
* Drug: Placebo comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe sepsis or septic shock with plasma activity of protein C < 60 % Exclusion Criteria: Pregnancy Risk of Bleeding Hemorragia age < 18

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human protein C concentrate<br> | Drug: Human protein C concentrate<br>* 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%<br>|
| Active Comparator: activated protein C<br>Continuous infusion of Activated Protein C | Drug: Activated protein C<br>* Continuous infusion of activated protein C at the dose of 24 micrograms/Kg/Hr for 96 hours<br>|
| Placebo Comparator: Placebo<br>Standard treatment | Drug: Placebo comparator<br>* Standard treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Human Protein C, Activated protein C, Microcirculation, Septic Shock