Modulation of Vasoreactivity in Septic Shock: Impact of Recombinant Protein C (PCA)

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Recombinant Activated Protein C; Device: Near-infrared spectroscopy (NIRS); Drug: Phenylephrine; Biological: Blood sample

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

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:

- 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Shock + Treatment; Patients treated with activated protein C	Drug: Recombinant Activated Protein C; 24 μg/kg/h during 96 hours - intravenous injection; Other Names: Xigris; Device: Near-infrared spectroscopy (NIRS); 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.; Drug: Phenylephrine; 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.; Biological: Blood sample; Analysis of inflammation and cellular adhesion markers and free radicals
Other: Shock; Patients not treated with activated protein C	Device: Near-infrared spectroscopy (NIRS); 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.; Drug: Phenylephrine; 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.; Biological: Blood sample; Analysis of inflammation and cellular adhesion markers and free radicals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Bruno LEVY, Réanimation Médicale - Hôpital de Brabois - CHRU Nancy

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: August 26, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (Estimate): August 31, 2016

Study Record Updates

• Last Update Posted (Estimate): August 31, 2016
• Last Update Submitted That Met QC Criteria: August 26, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: vasoreactivity; recombinant activated protein C
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Anticoagulants; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Phenylephrine; Oxymetazoline; Protein C; Drotrecogin alfa activated
• Other Study ID Numbers: 2007-002319-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO