Clinical trial NCT01501981: Impact of Therapy Optimization on the Level of Biomarkers in Patients With Decompensated Heart Failure
Official title: Impact of Therapy Optimization on the Level of Biomarkers in Patients With Acute Decompensated and Decompensated Chronic Heart Failure
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Decompensated Heart Failure
Keywords: heart failure
MR-proANP
MR-proADM
decompensation
Copeptin
CT-proET1
NT-proBNP
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Brahms AG
First posted: 2011-12-30
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients with acute decompensated and decompensated chronic heart failure

Brief summary: In this pilot, investigator-initiated multi-centre, multinational, observational study the investigators would like to examine the impact of therapy optimization on the level of biomarkers in patients with acute decompensated and decompensated chronic heart failure.

The primary objective is to determine the best time point for measuring biomarker levels during therapy optimization in patients with decompensation to predict clinical outcomes such as mortality, hospitalisation, and quality of life.

Secondary objectives are:

1. To evaluate the impact of guideline-recommended medication on biomarker levels during and following recompensation.
2. To evaluate whether the trajectory of relevant biomarkers (MR-proANP, MR-proADM) is of relevance to guide medical therapy following decompensation.
3. To evaluate whether the degree of biomarker change (e.g. slow versus rapid change) is of relevance with regard to hemodynamic stability and cardiovascular events such as hospitalisation.
4. To evaluate whether the trajectory of relevant biomarkers (copeptin, CT-pro-ET1) is of relevance to guide medical therapy following decompensation.


Eligibility criteria: Inclusion Criteria:

1. Male or female patients ≥ 18 years.
2. Hospitalized for ADHF or decompensated chronic heart failure. Patients who develop ADHF while hospitalized for another reason are not eligible.
3. The underlying primary etiology for decompensation should be cardiac rather than pulmonary disease. For this study, all of the following must be observable at the time of screening:

   * Dyspnea at rest (sitting or supine) or with minimal exertion (such as talking, eating, etc.) - NYHA III/IV;
   * Pulmonary congestion on physical examination or chest x-ray;
4. Able to begin study within 24 hours from presentation to the hospital, including time spent in the emergency department.
5. Be adequately informed of the nature and risks of the study and give written informed consent prior to study start.

Exclusion Criteria:

1. Acute or suspected acute myocardial infarction (AMI) or troponin levels \> 3x the upper limit of normal. at the institution's local laboratory.
2. Cardiogenic shock.
3. Temperature \> 38°C (oral or equivalent), sepsis or active infection requiring IV antimicrobial treatment.
4. ADHF due to significant arrhythmias (ventricular tachycardia, bradyarrhythmias with ventricular rate \< 45 bpm or atrial fibrillation/flutter with ventricular response of \> 150 bpm).
5. Current or planned ultrafiltration, hemofiltration, or dialysis.
6. Significant pulmonary disease (history of oral daily steroid dependency, history of CO2 retention or need for intubation for acute exacerbation, or currently receiving IV steroids), or thoracic cage injury which compromises breathing.
7. Any organ transplant recipient or patients currently listed or admitted for transplantation.
8. Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy (not including restrictive mitral valve filling patterns).
9. Women who are pregnant or breastfeeding.
10. Malignant disease with a life expectancy of less than two years.
11. Autoimmune disease.
12. Any condition or treatment of a condition which, in the opinion of the investigator, could interfere with the conduct of the study, or which would unacceptably increase the risk of the patient's participation in the study. This may include, but is not limited to, alcoholism, drug dependency or abuse, other severe mental disorders, epilepsy, or any unexplained episodes of syncope.

Primary outcomes:
measure: Time to first event - all cause death - cardiovascular death - all cause hospitalisation - cardiovascular hospitalisation - hospitalization for heart failure
timeFrame: from study start (day 1) during hosptialisation until second year of follow up
Secondary outcomes:
measure: quality of life
timeFrame: from study start (day 1) during hosptialisation until second year of follow up
measure: Six-minute walk test distance
timeFrame: from study start (day 1) during hosptialisation until second year of follow up
measure: Echocardiographic parameters
timeFrame: from study start (day 1) during hosptialisation until second year of follow up
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Campus Virchow Klinikum-Medizinische Klinik mit Schwerpunkt Kardiologie
Study officials:
References:
citation: Zelenak C, Chavanon ML, Tahirovic E, Trippel TD, Tscholl V, Stroux A, Veskovic J, Apostolovic S, Obradovic D, Zdravkovic M, Loncar G, Stork S, Herrmann-Lingen C, Dungen HD. Early NT-proBNP and MR-proANP associated with QoL 1 year after acutely decompensated heart failure: secondary analysis from the MOLITOR trial. Biomark Med. 2019 Dec;13(17):1493-1507. doi: 10.2217/bmm-2019-0083. Epub 2019 Oct 29.
citation: Dungen HD, Tscholl V, Obradovic D, Radenovic S, Matic D, Musial Bright L, Tahirovic E, Marx A, Inkrot S, Hashemi D, Veskovic J, Apostolovic S, von Haehling S, Doehner W, Cvetinovic N, Lainscak M, Pieske B, Edelmann F, Trippel T, Loncar G. Prognostic performance of serial in-hospital measurements of copeptin and multiple novel biomarkers among patients with worsening heart failure: results from the MOLITOR study. ESC Heart Fail. 2018 Apr;5(2):288-296. doi: 10.1002/ehf2.12231. Epub 2018 Feb 24.