Modulation of Vasoreactivity in Septic Shock: Impact of Recombinant Protein C

Study Overview
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Brief Summary
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The purpose is to demonstrate that vasoreactivity of patients with septic shock evaluated with dose-response curve is diminished in septic shock and ameliorated by activated protein C (APC). This amelioration is correlated to decrease of inflammation, decrease of reactive oxygen species (ROS) markers and increase of circulating catecholamines.

Official Title
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Modulation of Vasoreactivity in Septic Shock: Impact of Recombinant Protein C

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Recombinant Activated Protein C
* Device: Near-infrared spectroscopy (NIRS)
* Drug: Phenylephrine
* Biological: Blood sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients with septic shock as determined by standard criteria (including infection and severe infection) Exclusion Criteria: Pregnant women Absence of signed informed consent. Due to gravity of medical situation of patients, inclusion will be possible after informed consent of a family member. As soon as possible, an informed consent will be obtained by patient Contraindication to Xigris: evolutive internal bleeding , intracranial pathology, neoplasia or brain involvement, concomitant heparin therapy >= 15 IU/kg/h, known hemorrhagic diathesis except acute coagulopathy subsequent to sepsis, severe chronic liver disease, platelet count < 30000 x 10^6/L, high bleeding risk, known hypersensibility to drotrecogin alfa (activated), one of excipients or bovine thrombin

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Shock + Treatment<br>Patients treated with activated protein C | Drug: Recombinant Activated Protein C<br>* 24 μg/kg/h during 96 hours - intravenous injection<br>* Other names: Xigris;Device: Near-infrared spectroscopy (NIRS)<br>* After baseline measurement, cuff is blown up to obtain a muscular saturation at 40% and then deflated. Reactive hyperthermia is measured. It is considered as an index for endothelial function.<br>Drug: Phenylephrine<br>* Continuous administration of phenylephrine with electric syringe with increasing dosing levels: 0.0; 0.02; 0.05; 0.1; 0.2; 0.5; 0.75; 1.00; 1.50; 3.00; 4.50; 6.00; 9.00 et 12 µg/kg/min. Each level is maintained for 5 minutes. Administration of phenylephrine is stopped progressively with the same schema. Arterial tension through an invasive approach is measured during the test.<br>Biological: Blood sample<br>* Analysis of inflammation and cellular adhesion markers and free radicals<br>|
| Other: Shock<br>Patients not treated with activated protein C | Device: Near-infrared spectroscopy (NIRS)<br>* After baseline measurement, cuff is blown up to obtain a muscular saturation at 40% and then deflated. Reactive hyperthermia is measured. It is considered as an index for endothelial function.<br>Drug: Phenylephrine<br>* Continuous administration of phenylephrine with electric syringe with increasing dosing levels: 0.0; 0.02; 0.05; 0.1; 0.2; 0.5; 0.75; 1.00; 1.50; 3.00; 4.50; 6.00; 9.00 et 12 µg/kg/min. Each level is maintained for 5 minutes. Administration of phenylephrine is stopped progressively with the same schema. Arterial tension through an invasive approach is measured during the test.<br>Biological: Blood sample<br>* Analysis of inflammation and cellular adhesion markers and free radicals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular reactivity measured with dose-response to phenylephrine |  | baseline | 
| Vascular reactivity measured with dose-response to phenylephrine |  | 4 hours | 
| Vascular reactivity measured with dose-response to phenylephrine |  | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vasoreactivity, recombinant activated protein C