Administration of Protein C Concentrates in Adult Critically Ill Septic Patients

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.

Study Overview

• Status: Terminated
• Conditions: Sepsis
• Intervention / Treatment: Drug: Protein C concentrate

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20132
    • Ospedale San Raffaele di Milano, Italy

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Protein C concentrate
Experimental: Protein C concentrate	Drug: Protein C concentrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Composite endpoint of number of participant with mortality and/or prolonged ICU stay

Collaborators and Investigators

• Sponsor: Università Vita-Salute San Raffaele

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: July 25, 2012
• First Submitted That Met QC Criteria: October 11, 2012
• First Posted (Estimate): October 12, 2012

Study Record Updates

• Last Update Posted (Estimate): December 15, 2015
• Last Update Submitted That Met QC Criteria: December 14, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Protein C
• Other Study ID Numbers: OSR/40/04/12