Clinical trial NCT00390962: The "COSMOS"-Study (Copeptin in Osmoregulation and Stress Assessment)
Official title: Copeptin as a Novel Diagnostic and Prognostic Marker in the Management of Neurological and Neurosurgical Patients With Sodium Imbalance The "COSMOS"-Study (Copeptin in Osmoregulation and Stress Assessment)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stroke
Transient Ischemic Attack
Keywords: copeptin
vasopressin
Adh
SIADH
diabetes insipidus
stroke
risk factors
Neurological patients with ischemic and hemorrhagic stroke and patients undergoing intracranial surgery.
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2006-10-23
Enrollment: 469
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All consecutive patients who are admitted to the emergency department with an ischemic or hemorrhagic stroke or transient ischemic attach (TIA) according to the World Health organization criteria \[37\] with symptom onset within the last 3 days.

Brief summary: Sodium imbalance is common and an adverse prognostic factor in hospitalized patients. However, identifying the causes of sodium imbalance is challenging in clinical practice. Levels of antidiuretic hormone (ADH) are elevated in patients with stroke correlating with disease severity and stress level; however, its measurement is cumbersome. ADH is derived from a larger precursor peptide along with Copeptin, which is a more stable peptide directly mirroring the production of ADH. Copeptin can be assayed readily in plasma. Early prognostic factors to predict in-hospital mortality and medium/long-term outcome in critically ill neurological patients, are helpful to guide and tailor early decisions on treatment, discharge from the intensive care unit and application of interventions to prevent deterioration of neurological functions.

We hypothesize that copeptin will improve the diagnostic accuracy to diagnose sodium imbalances as compared to routinely used markers Furthermore, we hypothesize that Copeptin will be a reliable prognostic tool, dependent or independent of sodium imbalance, to predict short-term (i.e. in-hospital) and medium-term (i.e. 3 months) clinical outcome in stroke patients.

Detailed description: Background:

Sodium imbalance is common and an adverse prognostic factor in hospitalized patients. However, identifying the causes of sodium imbalance is challenging in clinical practice. Levels of antidiuretic hormone (ADH) are elevated in patients with stroke correlating with disease severity and stress level; however, its measurement is cumbersome. ADH is derived from a larger precursor peptide along with Copeptin, which is a more stable peptide directly mirroring the production of ADH. Copeptin can be assayed readily in plasma. Early prognostic factors to predict in-hospital mortality and medium/long-term outcome in critically ill neurological patients, are helpful to guide and tailor early decisions on treatment, discharge from the intensive care unit and application of interventions to prevent deterioration of neurological functions.

Aim: To evaluate Copeptin as a diagnostic tool in disturbances of water homeostasis and prognostic tool to predict outcome in a well-defined cohort of stroke patients and patients undergoing intracranial surgery.

Design: Prospective, observational study. Location Setting: Emergency and neurological and neurosurgical clinic of the University Hospital of Basel.

Patients: Neurological patients with ischemic and hemorrhagic stroke and patients undergoing intracranial surgery.

Intervention: After informed consent, all routinely determined baseline data will be assessed including medical history, clinical items (i.e. neurological status, volume status, pulse rate, blood pressure, weight) and laboratory items (i.e. urine / serum osmolality, electrolytes, among others). All patients will have a follow-up with clinical and laboratory assessment until the day of discharge. After 3 months, they will be followed-up by a structured telephone interview to assess outcome (mortality, morbidity, as assessed by the ranking scale and Barthel index). Copeptin will be assessed in a batch analysis upon completion of the plasma asseveration.

Variables and measurements: Baseline data on medical history and clinical items, co-morbidities and treatment procedures will be collected. This exploratory study will be conducted over a 12 month period from November 2006 to November 2007.

Study hypothesis: 1. Copeptin will improve the diagnostic accuracy to diagnose sodium imbalances as compared to routinely used markers 2. Copeptin will be a reliable prognostic tool, dependent or independent of sodium imbalance, to predict short-term (i.e. in-hospital) and medium-term (i.e. 3 months) clinical outcome in stroke patients.

Analysis: Our sample size consideration is based on the second prognostic question to predict the outcome of neurological and neurosurgical patients. To determine an optimal clinical model we will undertake a multivariable regression analysis to assess which variables are independently associated with outcome. Multiple regression models with a minimum of 10 to 15 observations per predictor variable reveal good estimates. We will evaluate 18 predictors in our multivariate analysis. Therefore, we aim to include a minimum sample size of 180 patients (for 10 observations per predictor) to 270 (for 15 observations per predictor) and a maximum sample size of 360 patients (for 20 observations per predictor).

Significance: Despite the frequent occurrence and the poor outcomes of serious disorders of sodium balance, few controlled data are available to guide the clinician. A better diagnostic approach to determine the etiology of hyponatremia should improve patient management. Copeptin as a prognostic marker in neurological and neurosurgical patients could become an innovative tool to guide early treatment decisions, discharge from the stroke unit and application of interventions.

Eligibility criteria: Inclusion Criteria:

1. All consecutive patients who are admitted to the emergency department with an ischemic or hemorrhagic stroke or transient ischemic attach (TIA) according to the World Health organization criteria \[37\] with symptom onset within the last 3 days.
2. All consecutive patients who undergo intracranial surgery due to

   * pituitary tumors
   * intracerebral hemorrhage (ICH)
   * subarachnoidal hemorrhage (SAH)
   * chronic subdural hematoma
   * head trauma with contusion cerebri
   * intracranial abcesses

Exclusion Criteria:

* Patients without informed consent.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: BS
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Beat Mueller, Prof
role: STUDY_CHAIR
References:
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