The Natural History of Procalcitonin in Hemorrhagic Stroke

Sponsor

CAMC Health System (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01498705

Collaborator

(none)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Approximately 12% of strokes in the United States are hemorrhagic.1 Hemorrhagic stroke can lead to multiple complications including fever that is not infectious. Identifying the cause of fever can help physicians choose the best care for the patient to try and prevent further damage to the already injured brain. Bacterial infection is one possible cause of fever in the stroke patient; however an incorrect diagnosis of infection can lead to unnecessary antibiotic use. Better screening tools for infection are being developed to help fight the problem of antibiotic resistance and unnecessary antibiotic use. Unnecessary use of antibiotics in patients increases the risk of adverse events and overall healthcare costs. Procalcitonin (PCT) is one such screening tool which has been used previously to help tell apart bacterial and nonbacterial causes of infection in other disease states; however, PCT has not been studied in hemorrhagic stroke patients. The purpose of this study is to understand the progress of PCT in hemorrhagic stroke patients in order to see whether PCT can be a useful marker for infection in these patients.

Condition or Disease	Intervention/Treatment	Phase
Intraventricular Hemorrhage Intracerebral Hemorrhage	Other: Procalcitonin level

Detailed Description

Stroke is the second leading killer worldwide and the third leading cause of death in the United States. The two major mechanisms causing brain damage in stroke are, ischemia and hemorrhage. Several complications can arise from these cerebral insults ranging from minor neurologic dysfunction, complete immobility, or death. In the intensive care setting, clinicians combat the pathophysiologic processes that lead to the aforementioned sequelae of stroke and contest other acute issues which may or may not be secondary to the stroke itself, with one such issue being hyperthermia. Hyperthermia is defined by the Society of Critical Care Medicine as a temperature greater than 38.3°C. In one prospective study, hyperthermia was reported to occur in 43% of patients during the first week of hospitalization following an ischemic or hemorrhagic (excluding subarachnoid hemorrhage) stroke. Hyperthermia in the stroke patient can be detrimental leading to increased infarct size and worsened neurological outcomes. The etiology of the hyperthermia may not be clear upon initial evaluation but cessation of fever is essential to prevent further damage.

One possible cause of hyperthermia in the stroke patient is bacterial infection. Infection complicating cerebral insult can lead to poor functional outcome and increased mortality. Kilpatrick and colleagues found that fever occurred in 47% of patients who were admitted with either a traumatic or ischemic brain injury and 70% of these patients received at least one antibiotic within 24 hours of their febrile episode, however the antibiotics had no effect on controlling the fevers. With bacterial resistance ever increasing, it is vital that clinicians reserve antibiotics for patients in whom the source of fever is believed to be secondary to an infectious process. It has been estimated that the United States health care system spends more than $20 billion annually on antibiotic-resistant infections and these infections result in more than eight million additional hospital days. Antibiotic use across health care disciplines has been estimated to be administered either inappropriately or unnecessarily 50% of the time. Considering clinical symptoms of infection can mirror other disease processes, reliable diagnostic biomarkers would be useful in helping determine the appropriate diagnosis.

PCT is a 116 amino acid peptide with a sequence identical to calcitonin but lacking hormonal activity. PCT was first utilized by Assicot et al in the setting of sepsis to help determine whether the inflammatory response from the patient was secondary to bacterial infection. Since this finding, PCT has been shown in several studies to have a high sensitivity and specificity for indicating systemic bacterial infections. During infection PCT is secreted into the bloodstream without increasing calcitonin. PCT has been shown prospectively to only be elevated in patients with bacterial infections while remaining consistently low in patients infected with viruses or other inflammatory processes. Often when insulted, the body utilizes proteins and metabolic products, and the changes noted in these substances are often used as markers of inflammation. Unlike erythryocyte sedimentation rate (ESR) and C-reactive protein (CRP), PCT remains low during these inflammatory states. Furthermore, it has been shown that PCT levels increase earlier after stimulation (3-6hrs) compared to C-reactive protein (12-24hrs), indicating PCT can be utilized to rapidly detect bacterial infections. Normal PCT levels in adults are less than 0.1 ng/mL while PCT values greater than 0.5ng/mL have been determined to be predictive of bacterial infection. PCT has been evaluated in several clinical scenarios to help determine a bacterial versus a non-bacterial source of infection, however, to our knowledge, the effects of hemorrhagic stroke on PCT are not yet known. Determining the natural history of PCT in a hemorrhagic stroke patient would provide beneficial information as to whether PCT can be used as a biomarker in this population to help differentiate a bacterial from a non-bacterial cause of hyperthermia.

Study Design

Study Type:

Observational

Actual Enrollment :

0 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

The Natural History of Procalcitonin in Hemorrhagic Stroke

Study Start Date :

Dec 1, 2011

Anticipated Primary Completion Date :

Jun 1, 2012

Anticipated Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Hemmorhagic Stroke Hospitalization for an admitting diagnosis of hemorrhagic stroke admitted to the neurosurgical intensive care unit Age greater than 18 years No evidence of ischemic cerebrovascular injury	Other: Procalcitonin level PCT level upon admission and on days 1, 3, and 5 following baseline level

Arm

Intervention/Treatment

Hemmorhagic Stroke

Hospitalization for an admitting diagnosis of hemorrhagic stroke admitted to the neurosurgical intensive care unit Age greater than 18 years No evidence of ischemic cerebrovascular injury

Other: Procalcitonin level

PCT level upon admission and on days 1, 3, and 5 following baseline level

Outcome Measures

Primary Outcome Measures

Natural progression of PCT following hemorrhagic stroke [Change in serum PCT level on day 0 (baseline) from serum PCT level day 1, 3, and 5.]

Secondary Outcome Measures

Markers of infection (if obtained by treating medical team) using SIRS criteria well as cultures. [From date of enrollment to 28 days or until death or discharge, whichever comes first.]
Sirs criteria: temperature < 36°C or > 38°C, heart rate > 90 beats/min, respiratory rate > 20 breaths/min, white blood cell count < 4000/mm² or > 12,000/mm² or ≥ 10% bands Cultures: blood, urine and sputum obtained by the treating medical team during study period and followed until final culture results are determined

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Hospitalization for an admitting diagnosis of hemorrhagic stroke admitted to the neurosurgical intensive care unit
Age greater than 18 years
No evidence of ischemic cerebrovascular injury

Exclusion Criteria:

Concomitant traumatic brain injury
Antibiotics on admission to the NICU
Immunocompromised by chemotherapy or HIV positive or patient with neutropenia (ANC <1000)
Women who are pregnant and/or of childbearing age where a pregnancy test has not already occurred