Clinical trial NCT03323216: BIO-2-HEART: Identification of Biomarkers in T2DM and Heart Failure
Official title: BIO-2-HEART Study (Identifying New BIOmarkers in Patients With Type 2 Diabetes Mellitus and HEArt Failure Receiving Cardiac Resynchronization Therapy Device Implantation)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Failure
Diabetes Mellitus, Type 2
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2017-10-26
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with and without heart failure (HFrEF, HFmrEF, HFpEF) plus known status of type 2 diabetes (yes/no)

Brief summary: The primary aim of the current study is a better understanding of the role of Type 2 Diabetes Mellitus (T2DM) in heart failure and, in particular, changes in cardiac metabolism, which may contribute to heart failure. Various biomarkers in the coronary artery blood, as well as in the arterial and peripheral venous blood, are to be identified for this purpose. Included are patients with and without T2DM and with or without heart failure (HFpEF, HFmrEF, HFrEF), who have a clinically indicated and guidance-appropriate Cardiac Resynchronisation Therapy (CRT) implantation or pulmonary vein ablation/electrophysiological examination.

Not all patients currently benefit from the implantation of a CRT system (so-called non-responder). Despite narrow inclusion criteria, these "non-responders" cannot be unmasked in advance of the implantation. A further aim of this study is to identify biomarkers, which can be determined in advance of implantation to differentiate between responders and non-responders.

Detailed description: The primary aim of the current study is a better understanding of the role of Type 2 Diabetes Mellitus (T2DM) in heart failure and, in particular, changes in cardiac metabolism, which may contribute to heart failure. Various biomarkers in the coronary artery blood, as well as in the arterial and peripheral venous blood, are to be identified for this purpose. Included are patients with and without T2DM, who have a clinically indicated and guidance-appropriate Cardiac Resynchronisation Therapy (CRT) implantation due to their cardiac insufficiency and patients who have a clinically indicated electrophysiological examination (EPU) or pulmonary vein ablation (PVI).

Not all patients currently benefit from the implantation of a CRT system (so-called non-responder). Despite narrow inclusion criteria, these "non-responders" cannot be unmasked in advance of the implantation. Thus, a further aim of this study is to identify biomarkers, which can be determined in advance of implantation to differentiate between responders and non-responders.

Patient selection is based on the previously defined inclusion and exclusion criteria. The patient is informed by the physician and gives written consent to participate in the study. Prior to the implantation of the CRT system/the electrophysiological examination(EPU)/pulmonary vein ablation(PVI), the patient first responds to a study-related questionnaire and performs a 6-minute walk test.

Afterwards the clinically indicated, elective CRT implantation/EPU/PVI is performed by experienced physicians of the Medical Clinic I. Routinely, an arterial pressure catheter for invasive blood pressure monitoring (usually arteria radialis) is inserted. In addition, 2 peripheral venous accesses are established. The system of the CRT system is carried out via a small pectoral section. The cardiac probes are inserted into the heart via the subclavian vein. First, the probe is implanted in the right ventricle and, if necessary, a probe is placed in the right atrium. For EPU/PVI a femoral vein acsess is established.

To establish the coronary sinus (CS) probe, the intubation of the coronary sinus is performed by means of a guide catheter, which can be used to take blood samples. After intubation of the coronary sinus, the coronary artery blood is taken from the guide catheter for the study as well as arterially via the underlying pressure catheter as well as peripheral venous over a horizontal venous catheter. During EPU/PVI the coronary sinus has also to be intubated due to the ablation protocol. The blood sampling does not take more than 1-2 minutes.

The surgery is then terminated as planned and postoperative care is performed according to the standard operation procedure (SOP) of the Medical Clinic I. Within the framework of a control visit routinely performed in the Medical Clinic I , an echocardiographic follow-up of heart failure, a history assessment and a laboratory-based blood analysis are performed 6 months after CRT implantation. In the context of this visit peripheral venous blood is collected again for the study. In addition, the 6-minute walk test is performed once more and the patient receives the same questionnaire again.

Laboratory routine blood analysis is performed in the central laboratory of the University Hospital of Aachen and is independent of the study. The analysis measures standard parameters such as electrolytes, blood count, retention parameters, glucose, HbA1c, liver values, N-terminal Brain Natriuretic Peptide (NT-pro-BNP) etc. .

A blood gas analysis of the study blood is performed out first. The remaining blood is processed and stored at -80 ° C, so-called "biobank", for further biomarker analysis, e.g. metabolite analysis, peptides/proteins and RNA.

Eligibility criteria: Inclusion Criteria:

1. guideline-appropriate clinical indication for CRT implantation/electrophysiologial examination/pulmonary vein ablation
2. age of majority
3. written declaration of consent
4. persons who are able to work and mentally able to follow the instructions of the study staff
5. free access routes

Exclusion Criteria:

1. anemia Hb \<8 mg / dl
2. patients with acute infectious disease (e.g. pneumonia)
3. non-intubatable coronary sinus
4. patients who do not have access to the subclavian vein (e.g. thrombosis of the subclavian vein or superior vena cava)
5. patients with idiopathic hypertrophic, restrictive or constrictive cardiomyopathy, or heart failure due to a known inflammatory or infiltrating disease (e.g. amyloidosis, sarcoidosis) or a constrictive disease
6. patients with heart failure by sepsis
7. persons with acute myocardial ischaemia, e.g. by angina pectoris or ECG changes under load
8. patients with acute coronary syndrome are not implanted in the past 3 months
9. patients who were hospitalized during the last month due to heart failure and who had to be treated intravenously with diuretics or inotropic substances
10. patients with mechanical aortic valve or tricuspid valve
11. patients with heart transplant.
12. patients with acute liver or renal failure
13. pregnant and lactating women
14. patients placed under an official or judicial order in an institution
15. patients who are in a dependency or employment relationship with the sponsor or auditor
16. taking an investigational medicinal product 30 days before the start of the study

Primary outcomes:
measure: Oxygen partial pressure (pO2) [mmHg]
timeFrame: Directly prior to the CRT-implantation
measure: Oxygen partial pressure (pO2) [mmHg]
timeFrame: 6 months after CRT-implantation
measure: Carbon dioxide partial pressure (pCO2) [mmHg]
timeFrame: Directly prior to the CRT-implantation
measure: Carbon dioxide partial pressure (pCO2) [mmHg]
timeFrame: 6 months after CRT-implantation
measure: potential of hydrogen (pH) value [-]
timeFrame: Directly prior to the CRT-implantation
measure: potential of hydrogen (pH) value [-]
timeFrame: 6 months after CRT-implantation
measure: Base excess [mmol]
timeFrame: Directly prior to the CRT-implantation
measure: Base excess [mmol]
timeFrame: 6 months after CRT-implantation
measure: Lactate [mmol/l]
timeFrame: Directly prior to the CRT-implantation
measure: Lactate [mmol/l]
timeFrame: 6 months after CRT-implantation
measure: Glucose [mg/dl]
timeFrame: Directly prior to the CRT-implantation
measure: Glucose [mg/dl]
timeFrame: 6 months after CRT-implantation
measure: Electrolytes (K+, Na2+, Ca2+) [mmol/l]
timeFrame: Directly prior to the CRT-implantation
measure: Electrolytes (K+, Na2+, Ca2+) [mmol/l]
timeFrame: 6 months after CRT-implantation
measure: High-sensitive troponin T [µg/L]
timeFrame: Directly prior to the CRT-implantation
measure: High-sensitive troponin T [µg/L]
timeFrame: 6 months after CRT-implantation
measure: Total creatine kinase [µg/L]
timeFrame: Directly prior to the CRT-implantation
measure: Total creatine kinase [µg/L]
timeFrame: 6 months after CRT-implantation
measure: Creatinine kinase-myocardial band (CK-MB) [µg/L]
timeFrame: Directly prior to the CRT-implantation
measure: Creatinine kinase-myocardial band (CK-MB) [µg/L]
timeFrame: 6 months after CRT-implantation
measure: Aspartate aminotransferase [µg/L]
timeFrame: Directly prior to the CRT-implantation
measure: Aspartate aminotransferase [µg/L]
timeFrame: 6 months after CRT-implantation
measure: Lactate dehydrogenase [µg/L]
timeFrame: Directly prior to the CRT-implantation
measure: Lactate dehydrogenase [µg/L]
timeFrame: 6 months after CRT-implantation
measure: N-terminal pro-B-type natriuretic peptide (NT-proBNP) [µg/L]
timeFrame: Directly prior to the CRT-implantation
measure: N-terminal pro-B-type natriuretic peptide (NT-proBNP) [µg/L]
timeFrame: 6 months after CRT-implantation
measure: High-sensitive C-reactive protein (CRP) [µg/L]
timeFrame: Directly prior to the CRT-implantation
measure: High-sensitive C-reactive protein (CRP) [µg/L]
timeFrame: 6 months after CRT-implantation
measure: Procalcitonin (PCT) [µg/L]
timeFrame: Directly prior to the CRT-implantation
measure: Procalcitonin (PCT) [µg/L]
timeFrame: 6 months after CRT-implantation
measure: Interleukin 6 (IL-6) [µg/L]
timeFrame: Directly prior to the CRT-implantation
measure: Interleukin 6 (IL-6) [µg/L]
timeFrame: 6 months after CRT-implantation
Secondary outcomes:
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: University Hospital RWTH Aachen
state: NRW
Study officials:
affiliation: Uniklinik RWTH Aachen
name: Ben Kappel, MD PhD
role: PRINCIPAL_INVESTIGATOR
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