Administration of Protein C Concentrates in Adult Critically Ill Septic Patients

Study Overview
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Brief Summary
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Severe sepsis and septic shock are life threatening medical emergencies and are among the most significant challenges in critical care. Case reports and case series suggest that plasma-derived protein C concentrate may improve the outcome of patients with acquired protein C deficiency. Evidence has accumulated on the clinical relevance of the PC pathway in modulating overwhelming inflammation and preventing coagulation derangements, two key mediators of organ damage, and thus of mortality and morbidity, in sepsis. The experience collected through these studies shows that PC is safe, in that it is not associated with bleeding or severe allergic complications,and possibly useful, at least to improve the coagulation abnormalities brought about by sepsis. Unfortunately, however, all we know comes from case series or case reports or an underpowered randomized controlled study. A randomized clinical trial, adequately powered for mortality or clinically relevant outcome, is necessary to confirm PC efficacy.The aim of this study is to demonstrate that Protein C zymogen has clinically relevant implications in terms of reduction of thromboembolic events, 30 days mortality, length of intensive care and hospital stay, time on mechanical ventilation, length of ICU and hospital stay. The study will also confirm that there is no bleeding concern with the use of Protein C concentrates.The study drug will be administered in the Intensive Care Unit for 72 hours and the patients observed till ICU discharge. Telephone followup will be performed at 30 days and at one year.

Official Title
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Administration of Protein C Concentrates in Adult Critically Ill Septic Patients

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Protein C concentrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Age > 18 years At least one of the following 3 criteria: venous-venous extra corporeal membrane oxygenation (ECMO) for septic adult respiratory distress syndrome (ARDS) septic disseminated intravascular coagulopathy (DIC) sepsis induced organ dysfunction associated with a clinical assessment of high risk of death Exclusion Criteria: Previous unusual response to PC or any of their components (murine proteins and heparin) PC administration or inclusion in other randomized protocols in the previous 30 days Do not resuscitate orders Refractory cardiogenic shock

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: Protein C concentrate<br> | Drug: Protein C concentrate<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Protein C concentrate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint of number of participant with mortality and/or prolonged ICU stay |  |  |