Evaluation of the Heparin Binding Protein Levels in Sepsis (HBP)

September 22, 2017 updated by: Christiana Care Health Services

Heparin Binding Protein (HBP) in Sepsis for the Prediction of Disease Progression

Present criteria used to define sepsis are non-specific, making it difficult to both distinguish sepsis from other diseases and to predict which patients are likely to become more severely ill. In standard care, patients at risk of becoming more severely ill are neither identified nor indicated for resuscitative efforts until they develop hemodynamic insufficiency or organ failure; after progression to severe disease, mortality increases significantly. The identification of risk patients can lead to earlier initiation of resuscitation therapies and potentially lead to reduced morbidity and mortality. This study aims to determine whether Heparin-binding protein (HBP), which is secreted from neutrophils during infection and a mediator of vascular leakage, can act as a biomarker for the progression to severe sepsis with circulatory failure.

The objective of this study is to validate the utility of HBP to predict the development of delayed onset organ dysfunction in sepsis in patients and to compare the performance of HBP relative to currently used prognostic biomarkers in sepsis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Sepsis is a heterogeneous disorder caused by an invasive infection that results in host inflammatory response. The underlying pathogenesis is complex and dependent on the etiologic microorganism, site of infection, and host factors. Present criteria defining sepsis (including change of body temperature, increased heart and respiration rates, and leukocytosis/leukopenia) are non-specific making it difficult to distinguish sepsis from other diseases and in particular to predict which patients are likely to become more severely ill. The consensus definition of sepsis has been debated over the past years and one suggested approach is to focus more on the presence of organ dysfunction. In standard care, patients at risk of becoming more seriously ill are not identified nor indicated for resuscitative efforts until they develop hemodynamic insufficiency or organ failure. However, after progression to severe disease mortality increases significantly. A recent study showed that almost a quarter of patients presenting with uncomplicated sepsis in an Emergency Department (ED) developed severe sepsis or septic shock within 72 hours. Delayed in-hospital progression to increased organ dysfunction was associated with increased transfer to the intensive care unit (ICU) and increased hospital length of stay. The identification of risk patients can lead to earlier initiation of resuscitation therapies and potentially lead to reduced morbidity and mortality. There are also increasing evidence that a single episode of severe sepsis has negative impact on quality of life and mortality several years after the actual incident. Also, recent studies indicate that less severe organ dysfunction, such as small increases in serum creatinine, are associated with increased long-term mortality among sepsis survivors.

Mechanisms that trigger the release of heparin-binding protein (HBP) from neutrophils in the presence of bacteria have previously been reported. HBP has several functions such as a chemo-attractant and as an activator of monocytes and macrophages. Also, it induces vascular leakage by interacting with the capillary endothelium and breaking cell barriers. In vivo studies have demonstrated that HBP released by the complex formed by the group A streptococcal M1 protein and fibrinogen induces a massive tissue edema contributing to severe organ damage. In clinical investigations, the release of HBP has been demonstrated in various infectious diseases caused by a wide array of bacteria. A recent single-center study of patients admitted for suspected infection and fever showed that plasma levels of HBP were significantly higher among patients who presented with or developed severe sepsis with circulatory failure.

A prospective observational study in a tertiary care Emergency Department. Patients must be identified and enrolled within 72 hours of qualifying inclusion criteria. At this time, unused blood samples collected for routine testing will be examined and the plasma level of HBP will be recorded; only blood samples processed by the lab within 3 hours of collection will be used. In addition, physiologic variables detailed in the data elements section, including mental status, metabolic, renal, heme, hepatic, respiratory, cardiovascular, resuscitation, and vasopressor use will be recorded. Patients who meet the inclusion criteria will be identified. Researchers will collect and record a resuscitation summary for a span of 4 hours; this data, outlined in the data elements section, will be linked to the quality improvement (QI) database of Sepsis Research. Additionally, the patient's HBP plasma levels will be measured from unused blood samples collected for routine lab testing time (T) 24, 48, and 72-hours (T24, T48, T72) after meeting the inclusion criteria (T0); resuscitation summaries will also be collected at T24, T48, T72. For patients meeting sepsis alert criteria, T0 will be defined as the time that the patient qualified; those enrolled based on Predisposition, Injury, Response, Organ dysfunction (PIRO) score will have T0 defined as the time hospital admission was ordered. Patients will be followed throughout their time in the hospital and their outcomes will be recorded.

Study Type

Observational

Enrollment (Actual)

1055

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Delaware
      • Newark, Delaware, United States, 19718
        • Christiana Care Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients admitted through the emergency department with infection.

Description

Inclusion Criteria:

  • Clinical diagnosis of a bacterial or viral infection
  • 18 years or older
  • Meet the sepsis alert criterion (Hypotension (BP < 90 after 2 L of fluids or lactate ≥ 4) OR
  • PIRO (Predispose, Infection, Response, Organ dysfunction ) score ≥ 15 .

Exclusion Criteria:

  • Minors (less than 18 years of age)
  • Patients who do not meet sepsis criteria as described above

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
24 Hours
HBP lab test performed 24 hours after meeting sepsis inclusion criteria.
Other: HBP lab test
Plasma level of Heparin Binding Protein will be evaluated on extra blood specimens already collected as part of standard of care.
Other Names:
  • Plasma level of heparin binding protein
48 Hours
HBP lab test performed 48 hours after meeting sepsis inclusion criteria.
Other: HBP lab test
Plasma level of Heparin Binding Protein will be evaluated on extra blood specimens already collected as part of standard of care.
Other Names:
  • Plasma level of heparin binding protein
72 Hours
HBP lab test performed 72 hours after meeting sepsis inclusion criteria.
Other: HBP lab test
Plasma level of Heparin Binding Protein will be evaluated on extra blood specimens already collected as part of standard of care.
Other Names:
  • Plasma level of heparin binding protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infection with organ dysfunction, defined as PIRO (Predisposition, Insult, Response, Organ Dysfunction) Score greater than 5
Time Frame: 72 hours after meeting sepsis criteria
Patients with septic shock or severe sepsis
72 hours after meeting sepsis criteria

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Christiana Care Health Services

Investigators

  • Principal Investigator: Ryan C. Arnold, MD, Christiana Care Health Services

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

July 1, 2017

Study Registration Dates

First Submitted

July 16, 2015

First Submitted That Met QC Criteria

August 24, 2015

First Posted (Estimate)

August 26, 2015

Study Record Updates

Last Update Posted (Actual)

September 25, 2017

Last Update Submitted That Met QC Criteria

September 22, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 602986

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sepsis

Clinical Trials on HBP lab test

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Portugal

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe