Trial document





This trial has been registered retrospectively.
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  DRKS00009906

Trial Description

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Title

Effect of beta-blocker therapy on infection rates after acute ischemic stroke: a prospective, multi-center observational study

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

Infections after acute ischemic stroke are frequent and associated with poor stroke outcome and increased risk of death. They can be caused by swallowing-disturbances and immobilisation. Beta-blockers are frequently prescribed drugs for high blood pressure, congestive heart failure and cardiac arrhytmias. They have been shown to also prevent stroke-induced immunodepression in experimental studies. Ischemic strokes in distinct brain regions hereby are associated with depression of the peripheral immune-system mediated by high levels of adrenalin (a hormone secreted in stressful situations). We assume, that beta-blockers can prevent these immunodepressive effects and therefore protect patients with ischemic stroke from developing infections. Aim of our study is to investigate the possible preventive effect of beta-blocker therapy prior to ischemic stroke on post stroke infection rates.

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Brief Summary in Scientific Language

Systemic infections are associated with poor outcome and increased mortality after ischemic
stroke. Post-stroke infection rates have been estimated to be 30%, with pneumonia and urinary tract infections (UTI) accounting
for the majority of cases. Recent experimental studies showed an active interaction between the central nervous system
and the peripheral immune system, which can result in immunosuppression and increased
susceptibility for systemic infections after stroke. This effect is thought to be a compensatory
response to protect the post-ischemic brain from overwhelming and damaging inflammatory
response. One of these immunosuppressive mechanisms after stroke is an activation of the sympathetic nervous system, resulting in an induction of anti-inflammatory phenotype immune cells. In patients with ischemic stroke, increased catecholamine levels and
decreased peripheral immune response have been described previously. Hyperactivity
of the sympathetic nervous system hereby is mainly caused by lesions of the anterior medial
cortex and insular cortex. Wong et al. investigated the mechanism of this inhibitory
pathway in a mice model and detected functional changes of invariant natural killer T (iNKT) cells after medial cerebral artery occlusion (MCAO). After MCAO, the iNKT cells showed an anti-inflammatory phenotype, resulting in a high incidence of infection and increased mortality. The authors demonstrated a complete reversion of the anti-inflammatory phenotype, a complete inhibition of mortality after systemic administration of the nonspecific beta-blocker propranolol. In a recently published retrospective study, we found decreased rates of urinary tract infections, but no difference in rates of post-stroke pneumonia, in patients with beta-blocker therapy prior to the index stroke. The aim of our study is to prospectively investigate the effect of commonly prescribed beta-blockers on the incidence of post-stroke infections and mortality.

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Organizational Data

  •   DRKS00009906
  •   2016/02/03
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  •   yes
  •   Approved
  •   7/7/15, Ethik-Kommission der Medizinischen Fakultät der Georg-August-Universität Göttingen
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Secondary IDs

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Health Condition or Problem studied

  •   I63.0 -  Cerebral infarction due to thrombosis of precerebral arteries
  •   J18.9 -  Pneumonia, unspecified
  •   N39.0 -  Urinary tract infection, site not specified
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Interventions/Observational Groups

  •   Aim of this study is to show a possible protective effect of prior and continued beta-blocker therapy on infection rates after acute ischemic stroke
  •   The control group includes patients without beta-blocker therapy prior to the acute ischemic stroke
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Other
  •   Open (masking not used)
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  •   Other
  •   Prevention
  •   Other
  •   N/A
  •   N/A
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Primary Outcome

Co-primary endpoint consisting of post-stroke pneumonia an urinary tract infection within 7 days after acute ischemic stroke according to diagnostic criteria of current guidelines

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Secondary Outcome

- Stroke outcome (modified Rankin Scale at baseline, after 7- and 30 days, National Institute of Health Stroke Scale at baseline and after 7 days)
- Infection-parameters (C-reactive protein and leukocyte-count after 7 days)
- Death

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • Medical Center 
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Recruitment

  •   Actual
  •   2015/12/01
  •   700
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   80   Years
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Additional Inclusion Criteria

Ischemic stroke in the insular and/or anterior-medial Cortex with an index NIHSS>4
Age >18 and <80 years

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Exclusion Criteria

-Systemic infection at baseline (index stroke) (elevated body temperature, leukocytosis >12*10^3 or C-reactive protein >10 mg/dl)
-Stroke onset >12 prior to admission
-Malignant primary disease
-Primary disease associated with immunodepression
-History of immunodepression (cytostatic-therapy within 1 month prior to index stroke, leukocytes <1000/µl, steroid-therapy (≥20 mg prednisolon-equivalent within 14 days prior to index stroke), immunodepressive therapy after organ transplant, known HIV-infection)
-Pre-stroke modified Rankin Scale >3
-Intracraneal hemorrhage
-Surgery within 30 days prior to index stroke

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Klinik für Neurologie
    • Mr.  PD Dr.  Jan  Liman 
    • Robert-Koch-Str. 40
    • 37075  Göttingen
    • Germany
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    • Klink für Neurologie
    • Mr.  Prof. Dr.  Pawel  Kermer 
    • Am Gut Sanderbusch 1
    • 26452  Sande
    • Germany
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    • Klinik für Neurologie
    • Mr.  Dr.  Ilko  Maier 
    • Robert-Koch-Str. 40
    • 37075  Göttingen
    • Germany
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    • Klinik für Neurologie
    • Mr.  Dr.  Ilko  Maier 
    • Robert-Koch-Str. 40
    • 37075  Göttingen
    • Germany
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Sources of Monetary or Material Support

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    • Klinik für Neurologie
    • Mr.  PD Dr.  Jan  Liman 
    • Robert-Koch-Str. 40
    • 37075  Göttingen
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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