New Biomarkers in Heart- and Renal Failure

Heart Failure Clinical Trial

— IM19 Register  

Official title:

New Biomarkers in Heart- and Renal Failure: Cohort Study for Assessing Prognosis in Acute Coronary Syndrome and Acute/Chronic Cardiovascular and Renal Failure by Means of Fibroblast Growth Factor 23

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02830464
• Other study ID #: 15-151
• Status: Completed
• Start date: August 2016
• Est. completion date: June 2018

Study information

• Verified date: October 2022
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In this study, prognostically relevant biomarkers for cardiovascular / renal insufficiencies will be clinically evaluated, to improve the course of assessment of such disease and to gain new insights into the typical course of congestive heart failure. This is a prerequisite to allow patients to appropriate treatment as soon as possible.

Description:

In recent years advances in diagnosis/ therapy in patients with acute coronary syndromes heart failure / and renal insufficiency patients could be made. However, these diseases still associated with an increased mortality rate. The diseases affecting at the same time as the heart and the kidney contribute to the deterioration in the course of the disease. An acute or chronic functional impairment of an organ, e.g. the heart, is connected to another functional impairment, such as the kidneys. In the past, different scores to the risk and prognosis assessment have been introduced measuring many different diagnostic parameters such as E.g. age, pre-existing conditions, kidney function, heart function, and laboratory values. The scores can be used for risk assessment and treatment. For determining the prognosis of heart and kidney-failure patients, biomarkers are analyzed. Biomarkers in the blood or urine which can provide early information on a specific course of disease are called prognostic biomarkers. In this study, prognostically relevant biomarkers for cardiovascular / renal insufficiencies will be clinically evaluated, to improve the course of assessment of such disease and to gain new insights into the typical course of congestive heart failure. This is a prerequisite to allow patients to appropriate treatment as soon as possible. An important role in heart and vascular disease can be awarded the Fibroblast growth factor 23 (FGF) 23. The height of FGF23 in the blood plasma is linked with the risk of cardiovascular events occur and the beginning of dialysis patients. FGF23 goes hand in hand with the development of heart failure or with a hospitalization as a result of heart failure. The clinical utility of biomarkers will be examined in relation to established risk scores calculated from clinical parameters, to determine whether this biomarker of bone-heart-kidney axis can extend the forecast evaluation of patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: June 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. at least 18 years old

2. signed informed consent

3. persons who are legally competent and mentally able to follow the instructions of study personnel

4. Patient with:

• NSTEMI myocardial infarction = non ST-segment elevation: unstable Angina pectoris (AP) / heart attack with rise of Troponin I or T, but without ST track elevation
• STEMI = ST-segment-elevation myocardial infarction: cardiac troponin T/where to sleep and enzyme changes and attack typical ECG changes (initial ST Elevation)
• Acute heart failure with need of hospitalisation
• Chronic heart failure decompensation and need to the hospitalisation and need for establishing primary > 12 hours on the station IM19 (conservative intermediate care station)

Exclusion Criteria:

1. less than 18 years old

2. pregnant women and breastfeeding women

3. previous recording on an intensive care unit or transfer to an intensive care unit within 12 h after admission the IM19 station

4. death within 12 h after admission

5. persons who are housed on official or judicial order in an institution

6. persons who are in a dependency or employment relationship to the sponsor or investigator

7. chronic dialysis patients

8. persons , who at the same time take part in another study

Related Conditions & MeSH terms

• Heart Failure
• Kidney Failure
• Renal Insufficiency

Locations

Country	Name	City	State
Germany	University Hospital RWTH Aachen	Aachen	NRW

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

References & Publications (22)

Anwaruddin S, Lloyd-Jones DM, Baggish A, Chen A, Krauser D, Tung R, Chae C, Januzzi JL Jr. Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study. J Am Coll Cardiol. 2006 Jan 3;47(1):91-7. Epub 2005 Dec 9. — View Citation

Brandenburg VM, Kleber ME, Vervloet MG, Tomaschitz A, Pilz S, Stojakovic T, Delgado G, Grammer TB, Marx N, März W, Scharnagl H. Fibroblast growth factor 23 (FGF23) and mortality: the Ludwigshafen Risk and Cardiovascular Health Study. Atherosclerosis. 2014 Nov;237(1):53-9. doi: 10.1016/j.atherosclerosis.2014.08.037. Epub 2014 Aug 28. — View Citation

Braunwald E. Biomarkers in heart failure. N Engl J Med. 2008 May 15;358(20):2148-59. doi: 10.1056/NEJMra0800239. Review. — View Citation

Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, Gutiérrez OM, Aguillon-Prada R, Lincoln J, Hare JM, Mundel P, Morales A, Scialla J, Fischer M, Soliman EZ, Chen J, Go AS, Rosas SE, Nessel L, Townsend RR, Feldman HI, St John Sutton M, Ojo A, Gadegbeku C, Di Marco GS, Reuter S, Kentrup D, Tiemann K, Brand M, Hill JA, Moe OW, Kuro-O M, Kusek JW, Keane MG, Wolf M. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011 Nov;121(11):4393-408. doi: 10.1172/JCI46122. Epub 2011 Oct 10. — View Citation

Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004 Sep 23;351(13):1296-305. Erratum in: N Engl J Med. 2008;18(4):4. — View Citation

Grabner A, Amaral AP, Schramm K, Singh S, Sloan A, Yanucil C, Li J, Shehadeh LA, Hare JM, David V, Martin A, Fornoni A, Di Marco GS, Kentrup D, Reuter S, Mayer AB, Pavenstädt H, Stypmann J, Kuhn C, Hille S, Frey N, Leifheit-Nestler M, Richter B, Haffner D, Abraham R, Bange J, Sperl B, Ullrich A, Brand M, Wolf M, Faul C. Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy. Cell Metab. 2015 Dec 1;22(6):1020-32. doi: 10.1016/j.cmet.2015.09.002. Epub 2015 Oct 1. — View Citation

Gutiérrez OM, Januzzi JL, Isakova T, Laliberte K, Smith K, Collerone G, Sarwar A, Hoffmann U, Coglianese E, Christenson R, Wang TJ, deFilippi C, Wolf M. Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation. 2009 May 19;119(19):2545-52. doi: 10.1161/CIRCULATIONAHA.108.844506. Epub 2009 May 4. — View Citation

Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol. 2013;75:503-33. doi: 10.1146/annurev-physiol-030212-183727. Review. — View Citation

Ix JH, Katz R, Kestenbaum BR, de Boer IH, Chonchol M, Mukamal KJ, Rifkin D, Siscovick DS, Sarnak MJ, Shlipak MG. Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study). J Am Coll Cardiol. 2012 Jul 17;60(3):200-7. doi: 10.1016/j.jacc.2012.03.040. Epub 2012 Jun 13. — View Citation

Kestenbaum B, Sachs MC, Hoofnagle AN, Siscovick DS, Ix JH, Robinson-Cohen C, Lima JA, Polak JF, Blondon M, Ruzinski J, Rock D, de Boer IH. Fibroblast growth factor-23 and cardiovascular disease in the general population: the Multi-Ethnic Study of Atherosclerosis. Circ Heart Fail. 2014 May;7(3):409-17. doi: 10.1161/CIRCHEARTFAILURE.113.000952. Epub 2014 Mar 25. — View Citation

Koller L, Kleber ME, Brandenburg VM, Goliasch G, Richter B, Sulzgruber P, Scharnagl H, Silbernagel G, Grammer TB, Delgado G, Tomaschitz A, Pilz S, Berger R, Mörtl D, Hülsmann M, Pacher R, März W, Niessner A. Fibroblast Growth Factor 23 Is an Independent and Specific Predictor of Mortality in Patients With Heart Failure and Reduced Ejection Fraction. Circ Heart Fail. 2015 Nov;8(6):1059-67. doi: 10.1161/CIRCHEARTFAILURE.115.002341. Epub 2015 Aug 13. — View Citation

Ky B, Shults J, Keane MG, Sutton MS, Wolf M, Feldman HI, Reese PP, Anderson CA, Townsend RR, Deo R, Lo J, Gadegbeku C, Carlow D, Sulik MJ, Leonard MB; CRIC Study Investigators. FGF23 modifies the relationship between vitamin D and cardiac remodeling. Circ Heart Fail. 2013 Jul;6(4):817-24. doi: 10.1161/CIRCHEARTFAILURE.112.000105. Epub 2013 Jun 7. — View Citation

Levy WC, Mozaffarian D, Linker DT, Sutradhar SC, Anker SD, Cropp AB, Anand I, Maggioni A, Burton P, Sullivan MD, Pitt B, Poole-Wilson PA, Mann DL, Packer M. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation. 2006 Mar 21;113(11):1424-33. Epub 2006 Mar 13. — View Citation

Lutsey PL, Alonso A, Selvin E, Pankow JS, Michos ED, Agarwal SK, Loehr LR, Eckfeldt JH, Coresh J. Fibroblast growth factor-23 and incident coronary heart disease, heart failure, and cardiovascular mortality: the Atherosclerosis Risk in Communities study. J Am Heart Assoc. 2014 Jun 10;3(3):e000936. doi: 10.1161/JAHA.114.000936. — View Citation

O'Connor CM, Hasselblad V, Mehta RH, Tasissa G, Califf RM, Fiuzat M, Rogers JG, Leier CV, Stevenson LW. Triage after hospitalization with advanced heart failure: the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) risk model and discharge score. J Am Coll Cardiol. 2010 Mar 2;55(9):872-8. doi: 10.1016/j.jacc.2009.08.083. — View Citation

Olauson H, Vervloet MG, Cozzolino M, Massy ZA, Ureña Torres P, Larsson TE. New insights into the FGF23-Klotho axis. Semin Nephrol. 2014 Nov;34(6):586-97. doi: 10.1016/j.semnephrol.2014.09.005. Review. — View Citation

Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP, Jacobsen SJ. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004 Jul 21;292(3):344-50. — View Citation

Sabatine MS, Antman EM. The thrombolysis in myocardial infarction risk score in unstable angina/non-ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2003 Feb 19;41(4 Suppl S):89S-95S. Review. — View Citation

Scialla JJ, Wolf M. Roles of phosphate and fibroblast growth factor 23 in cardiovascular disease. Nat Rev Nephrol. 2014 May;10(5):268-78. doi: 10.1038/nrneph.2014.49. Epub 2014 Apr 1. Review. — View Citation

Scialla JJ, Xie H, Rahman M, Anderson AH, Isakova T, Ojo A, Zhang X, Nessel L, Hamano T, Grunwald JE, Raj DS, Yang W, He J, Lash JP, Go AS, Kusek JW, Feldman H, Wolf M; Chronic Renal Insufficiency Cohort (CRIC) Study Investigators. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol. 2014 Feb;25(2):349-60. doi: 10.1681/ASN.2013050465. Epub 2013 Oct 24. — View Citation

Sitara D, Kim S, Razzaque MS, Bergwitz C, Taguchi T, Schüler C, Erben RG, Lanske B. Genetic evidence of serum phosphate-independent functions of FGF-23 on bone. PLoS Genet. 2008 Aug 8;4(8):e1000154. doi: 10.1371/journal.pgen.1000154. — View Citation

Tang WH, Francis GS, Morrow DA, Newby LK, Cannon CP, Jesse RL, Storrow AB, Christenson RH, Apple FS, Ravkilde J, Wu AH; National Academy of Clinical Biochemistry Laboratory Medicine. National Academy of Clinical Biochemistry Laboratory Medicine practice guidelines: Clinical utilization of cardiac biomarker testing in heart failure. Circulation. 2007 Jul 31;116(5):e99-109. Epub 2007 Jul 14. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival after recording on the intermediate care station		35 days
Secondary	Survival after recording on the intermediate care station		12 months
Secondary	Major adverse cardiac events		12 months
Secondary	Rehospitalisation due to cardiovascular cause		12 months