Trial document





This trial has been registered retrospectively.
drksid header

  DRKS00016852

Trial Description

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Title

Berlin Longterm Observation of Vascular Events - Pilot study

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Trial Acronym

BeLOVE - Pilot study

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URL of the Trial

http://www.bihealth.org/belove

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Brief Summary in Lay Language

BeLOVE stands for „Berlin Longterm Observation of Vascular Events“ and is a so called cohort study. Within the scope of BeLOVE diseases affecting metabolism or heart and vascular system will be studied. Cardiovascular diseases belong to the worldwide most common diseases and contribute fundamentally to the disease burden of our society. The analysis of as much as possible study and patient data, investigations of many different biomaterials combined with the execution of medical examinations may help to improve our understanding for the development of those diseases. This may contribute in future to a quicker identification of cardiovascular diseases, to an improved treatment of patients and to the development of more effective preventive measures and therapies.
Patients with acute myocardial infarction, after acute decompensated heart failure, after acute stroke, with acute kidney failure or with type 2 diabetes mellitus will be enrolled in this study. The objectives of BeLOVE are: to investigate the relationship of the different disease entities (metabolic and cardiovascular) in a comprehensive way. For this purpose, the establishment of a large study cohort is essential. Based on this, predictive models for the progression of metabolic and cardiovascular diseases will be developed and biomarkers will be identified, that play an important role in the development and course of these diseases. The aim of the pilot phase is to evaluate the overall feasibility of the project and to create the conditions for further refinement of the study in the main phase.

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Brief Summary in Scientific Language

Cardiovascular disease (CVD) is the leading cause of premature death worldwide with multiple forms of organ dysfunction, comorbidities, impaired health-related quality of life as well as frailty and dependency in the elderly. The greatest contribution to increased life expectancy between 1980 and 2002 is a reduction in age-specific mortality from cardiovascular diseases. Therefore, it is still necessary to collect and analyze data on development and progression of cardiovascular diseases in order to find new predictors for vascular events. The Berlin Longterm Observation of Vascular Events (BeLOVE) study is designed as a patient-based cohort study to provide a unique scientific structure and high quality data/biomaterial resource for a variety of studies on risk factors, interactions and causal mechanisms of different forms of CVD manifestations in a high-risk population.
The objective of BeLOVE is to identify novel pathophysiological cross-disease mechanisms and treatment targets that determine both short and long-term outcome of high-risk patients with acute vascular disease. In the pilot phase of the study we intend the inclusion of 1300 patients with an acute index events due to acute cerebrovascular disorder, acute coronary syndrome, acute heart failure, and acute kidney injury together with patients with type 2 diabetes mellitus, also known to be at high risk to develop a cardiovascular event (one cohort – five disease entities). The aim of the pilot phase is to evaluate the overall feasibility of the project and to create the conditions for further refinement of the study in the main phases, in particular 1.) establishing liaisons with the trial teams of the Charité clinics as well as with core units, e.g. for imaging or biobanking, 2.) consolidating the procedures necessary to characterize the patients and 3.) evaluating the necessary steps required to perform the study with a substantially higher number of participants.

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Organizational Data

  •   DRKS00016852
  •   2019/04/05
  •   [---]*
  •   yes
  •   Approved
  •   EA1/066/17, Ethik-Kommission der Charité -Universitätsmedizin Berlin-
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   I21 -  Acute myocardial infarction
  •   I61 -  Intracerebral haemorrhage
  •   I63 -  Cerebral infarction
  •   E11 -  Type 2 diabetes mellitus
  •   N17 -  Acute renal failure
  •   I67.6 -  Nonpyogenic thrombosis of intracranial venous system
  •   H34.1 -  Central retinal artery occlusion
  •   H47.0 -  Disorders of optic nerve, not elsewhere classified
  •   G45.0 -  Vertebro-basilar artery syndrome
  •   G45.1 -  Carotid artery syndrome (hemispheric)
  •   G45.2 -  Multiple and bilateral precerebral artery syndromes
  •   G45.3 -  Amaurosis fugax
  •   G45.9 -  Transient cerebral ischaemic attack, unspecified
  •   I11.0 -  Hypertensive heart disease with (congestive) heart failure
  •   I13.0 -  Hypertensive heart and renal disease with (congestive) heart failure
  •   I13.2 -  Hypertensive heart and renal disease with both (congestive) heart failure and renal failure
  •   I13.9 -  Hypertensive heart and renal disease, unspecified
  •   I42 -  Cardiomyopathy
  •   I50.0 -  Congestive heart failure
  •   I50.13 -  [generalization I50.1: Left ventricular failure]
  •   I50.14 -  [generalization I50.1: Left ventricular failure]
  •   I50.19 -  [generalization I50.1: Left ventricular failure]
  •   I50.9 -  Heart failure, unspecified
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Interventions/Observational Groups

  •   Patients with acute myocardial infarction, after acute decompensated heart failure, after acute stroke, with acute kidney failure or with type 2 diabetes mellitus will be followed up over 10 years. There will be yearly telephone visits, as well as an acute phenotyping at the time of enrollment and 3 deep phenotyping visits after 90 days, 2 years and 5 years.
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Prognosis
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Composite endpoint consisting of: cardiovascular mortality, non-fatal stroke, non-fatal myoracial infarction, rehospitalization due to heart failure

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Secondary Outcome

1. Cardiovascular morbidity (cardiac insufficiency, coronary heart disease, revascularization, TIA. Myocardial infarction or stroke are appraised as secondary instead of primary endpoints when the composite primary endpoint has already been reached beforehand).

2. overall mortality.

3. course / manifestation of cardiovascular risk factors (glucose, lipids, blood pressure, renal insufficiency, etc.).

4. the importance of the physical condition (for example, dexterity) on health-related quality of life, tendency to fall, age dependency and on new cardiovascular Events.

5. Significance of cognitive (e.g., memory) and mental (e.g., depressive) condition related to health-related quality of life, tendency to fall, retirement, and new cardiovascular events,

6. manifestation of atrial fibrillation.

7. Independency in everyday life (by degree of nursing).

8. intra-abdominal, intra-myocellular and intra-hepatic fat.

9. Significance of glucose variability (inter-day and intra-day) with respect to cardiovascular outcomes (event / re-event).

10. the importance of body fat distribution and the intra-abdominal hepatic and intramuscular fat distribution pattern for cardiovascular risk.

11. the importance of stress-induced (test meal versus physical stress) metabolic (lipids, glucometabolites, amino acids, etc.) changes related to the new Event.

12. Changes of kidney function during follow-up
- Incident chronic kidney disease (CKD)
- Progression of CKD
- New onset of end stage renal disease (ESRD)

13. Major adverse kidney events (MAKE), defined as a 25% reduction of eGFR or new onset of ESRD or death.

14. New onset of ESRD or 25% reduction of eGFR.

15. New or recurrent AKI episodes.

16. Relevance of peripheral neuropathy (measured by questionnaires, clinical as well as neurophysiological examination), neuropathic pain and autonomic neuropathy (measured by questionnaire and heart rate variability) in predicting microangiopathy (fundus photography, optical coherence tomography), macroangiopathy (pw-velocity, echocardiography, carotid IMD) and clinical vascular events in patients with diabetes, prediabetes and subgroups of patients with AKI, stroke or cardiovascular disease

17. Pathomechanisms (e.g. hyperglycemia, dyslipidemia etc.) linking peripheral diabetic neuropathy and vascular disease.

18. Significance of neural connectivity patterns (measured by resting state EEG) with respect to brain-morphology (MRI), stroke outcome (quality of life, physical performance) and stroke risk

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2017/07/18
  •   1300
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

provision of signed and dated informed consent form
2) declared willingness to take part in study procedures and to be contacted again for further
follow-up examinations
3) persons of any sex and gender, aged 18 years or above at the time of acute event or study
inclusion
4) general health status is acceptable for participation in a study
5) clinical diagnosis of one or more of the following diseases:
A) acute heart failure (trigger event), defined by:
i) dyspnoe NYHA IIIb or IV and NTproBNP ≥ 300 pg/nl OR
MRproANP ≥ 120 pmol/l, AND

ii) evidence of pitting peripheral edema or radiological or clinical signs of
of pulmonary congestion, AND
iii) Need for i.v.-administration or dose escalation of diuretic therapie
equivalent to furosemid 40 mg or torasemid of 10 mg.

B) acute coronary syndrome (trigger event), defined by:
i) acute cardiac chest pain, or angina equivalent consistent with moderate to high-
risk unstable angina or myocardial infarction, lasting more than 10 minutes
duration during72 hours before invasive examination, AND
ii) evidence for ACS requiring catheterization documented by
(1) elevated enzymes (CK-MB or hs-troponin i/T >99th percentile or in-
/decrease) AND/OR
(2) ECG with ST-depression >1mm in 2 or more contiguous leads after the
J-point AND/OR
(3) transient ST-elevation >1mm in 2 or more contiguous leads lasting
<30 min OR
(4) STE-ACS with onset <24 hours previously and chest pain > 30 min
ST-elevation > 1mm in 2 or more contiguous leads or new left bundle block

C) acute cerebrovascular disorders (trigger event), defined by:
i) a transient ischemic attack (TIA) with clinical restitution within 24h AND
initial neurological deficit verified by a neurologist OR ABCD2-Score >= 3 OR
visibleDWI-lesion (MRI) OR the main hospital diagnosis of Amaurosis fugax
ii) Ischemic stroke including retinal central artery occlusion
iii) stroke caused by non-traumatic intracerebral hemorrhage
iv) stroke caused by cerebral venous thrombosis

D) acute kidney injury while hospitalized, that occurred 3-8 days before study inclusion
(trigger event), defined by:
i) >= 2fold increase in creatinine compared to a respective value during a presumed
or documented time period (stage 2 or 3 acute kidney injury according to KDIGO)
ii) persistence of the increased value for at least 72 hrs

E) diabetes mellitus type 2 (at day 60)
i) known diabetes mellitus type 2 characterized by
(1) pathological findings in oral glucose tolerance test, OR
(2) documented HbA1c >= 6.5%, OR
(3) Intake of any antidiabetic medication
ii) prediabetes with high cardiovascular risk, characterized by
(1) HbA1c >5.7% and <6.5% AND an ESC score >= 5

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Exclusion Criteria

1) lack of capacity to give informed consent
2) pregnancy or lactation
3) life expectancy < 6 months due to non‐cardio‐/cerebrovascular diseases or conditions
4) organ transplanted
5) Lack of health insurance

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Addresses

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    • Charité Universitätsmedizin Berlin
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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    • Experimental and Clinical Research Center & Max-Delbrück Center
    • Mr.  Prof. Dr.   Dominik  Müller 
    • Lindenberger Weg 80
    • 13125  Berlin
    • Germany
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    • Berlin Institute of Health (BIH)
    • Ms.  Dr.  Kathrin  Haubold 
    • Anna-Louisa-Karsch-Str. 2
    • 10178   Berlin
    • Germany
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Sources of Monetary or Material Support

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    • Berlin Institute of Health (BIH)
    • Anna-Lousia-Karsch-Str. 2
    • 10178  Berlin
    • Germany
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Status

  •   Recruiting ongoing
  •   [---]*
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.