The Natural History of Procalcitonin in Hemorrhagic Stroke

This study has been withdrawn prior to enrollment.
(Anticipated grant was withdrawn and additional funding was unable to be obtained)
Sponsor:
Information provided by (Responsible Party):
Carol Morreale, CAMC Health System
ClinicalTrials.gov Identifier:
NCT01498705
First received: December 20, 2011
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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 Intervention
Intraventricular Hemorrhage
Intracerebral Hemorrhage
Other: Procalcitonin level

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Natural History of Procalcitonin in Hemorrhagic Stroke

Resource links provided by NLM:


Further study details as provided by CAMC Health System:

Primary Outcome Measures:
  • Natural progression of PCT following hemorrhagic stroke [ Time Frame: Change in serum PCT level on day 0 (baseline) from serum PCT level day 1, 3, and 5. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Markers of infection (if obtained by treating medical team) using SIRS criteria well as cultures. [ Time Frame: From date of enrollment to 28 days or until death or discharge, whichever comes first. ] [ Designated as safety issue: No ]
    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


Biospecimen Retention:   Samples Without DNA

3 mL of blood will be obtained for each PCT sample and will be sent to the Virology lab at CAMC Memorial hospital where the serum will be frozen until all samples are collected. After all samples from each of the 30 patients are obtained, the specimens will be analyzed for the PCT value and then discarded.


Enrollment: 0
Study Start Date: December 2011
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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
Other Name: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients admitted to the Neurosurgical ICU with a diagnosis of intraventricular or intracerebral hemorrhage

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01498705

Locations
United States, West Virginia
Charleston Area Medical Center
Charleston, West Virginia, United States, 25301
Sponsors and Collaborators
CAMC Health System
Investigators
Principal Investigator: Douglas W Haden, MD WVU School of Medicine/Charleston Division
  More Information

Publications:
Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EF; American Heart Association; American Stroke Association Stroke Council; Clinical Cardiology Council; Cardiovascular Radiology and Intervention Council; Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007 May;38(5):1655-711. Epub 2007 Apr 12. Erratum in: Stroke. 2007 Jun;38(6):e38. Stroke. 2007 Sep;38(9):e96.

Responsible Party: Carol Morreale, Clinical Pharmacist Specialist, CAMC Health System
ClinicalTrials.gov Identifier: NCT01498705     History of Changes
Other Study ID Numbers: 1997096
Study First Received: December 20, 2011
Last Updated: January 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by CAMC Health System:
Intraventricular Hemorrhage
Intracerebral Hemorrhage
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Procalcitonin Level

Additional relevant MeSH terms:
Hemorrhage
Cerebral Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 02, 2014