N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) in Type 2 Diabetes Mellitus

Heart Failure Clinical Trial

— PISCES  

Official title:

Performance of NT-proBNP in Risk Stratification for Cardiovascular Events and Mortality in Patients With Diabetes (PISCES)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05745090
• Other study ID #: PISCES2022
• Status: Active, not recruiting
• Start date: November 10, 2022
• Est. completion date: April 30, 2029

Study information

• Verified date: April 2024
• Source: Singapore General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

More than 400 million people have type 2 diabetes (T2D) globally, and the burden of diabetes-related cardiovascular complications is increasing. Cardiovascular disease (CVD) affects approximately one-third of all individuals with T2D and accounts for half of all deaths in this population despite major advances in the treatment of the disease. Among the different types of CVD, heart failure (HF) is frequently the first CVD manifestation in individuals with T2D. Although the link between T2D and CVD is widely recognised, the absolute risk of cardiovascular events varies among individuals with T2D. As such, effective risk-stratification tool that accurately identify T2D patients at the highest risk of developing incident or recurrent cardiovascular (CV) events is needed. B-type natriuretic peptide (BNP) and its inactive N-terminal precursor NT-proBNP are biomarkers of myocardial stress. They been shown to incrementally improve predictive discrimination of death and CV events in high-risk individuals with T2D. An NT-proBNP-based CVD/HF risk stratification strategy has not been prospectively tested in the multi-ethnic T2D population in Singapore. In this study, we aim to: 1. Evaluate the predictive value of NT-proBNP for death and CV events compared to traditional risk markers [e.g. HbA1c, albuminuria, high sensitivity C-reactive protein (hsCRP), high sensitivity troponin-T (hsTnT)] in a cohort of T2D patients with or without established CVD (defined as ischaemic heart disease, myocardial infarct, unstable angina, prior coronary artery revascularisation, stroke, transient ischaemic attack or PAD) attending a tertiary diabetes care centre. (Patients with history of HF will be excluded.) 2. Compare the performance of NT-proBNP as a single biomarker for CV risk prediction to risk scoring algorithms in T2D patients.

Description:

This is a prospective single-site, observational study to evaluate the predictive value of NT-proBNP for death and CV events compared to traditional CV risk markers (e.g., HbA1c, albuminuria, hsCRP and hsTnT) in T2D patients with or without established CVD (defined as ischaemic heart disease, myocardial infarct, unstable angina, prior coronary artery revascularisation, stroke, transient ischaemic attack or PAD). Patients with history of HF will be excluded. The study will also compare the performance of NT-proBNP as a single biomarker for CV risk prediction to other risk scoring algorithms such as UK Prospective Diabetes Study (UKPDS) risk engine, Risk Equations for Complications Of Type 2 Diabetes (RECODe) and University of Hong Kong-Singapore (HKU-SG) risk scores. The study will prospectively recruit 1200 adults (aged 40 and above) with T2D from Singapore General Hospital (SGH) over a period of 18 months. Informed consent will be obtained from patients before the start of any procedures. There will be 1 baseline visit to collect demographic information, and clinical and laboratory data. Baseline point-of-care echocardiography will also be performed for all patients. All patients will subsequently be observed over 5 years for the occurrence of death or CV events through monitoring of electronic health records (EHR) and telephone contacts.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1200
• Est. completion date: April 30, 2029
• Est. primary completion date: March 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 99 Years

Eligibility

Inclusion Criteria:

1. Type 2 diabetes (T2D) of at least 6 months' duration

2. Age 40 and older

Exclusion Criteria:

1. Known history of heart failure (self-reported and medical records review)

2. Estimated glomerular filtration rate (eGFR) <15 ml/min/1.73m2 [using the CKD-Epidemiology Collaboration (CKD-EPI) 2021 equation for glomerular filtration rate] based on the last known eGFR within 12 months of study recruitment)

3. Renal replacement therapy

4. Systemic treatment with corticosteroids or immunosuppressants

5. Pregnant or nursing women

6. Active cancer disease

7. Serious disease with life expectancy <1 year as judged by the doctor

8. Any condition that, in the investigator's opinion, would interfere with a subject's ability to comply with study protocol or procedures

Related Conditions & MeSH terms

• Cardiovascular Complication
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Heart Failure

Locations

Country	Name	City	State
Singapore	Singapore General Hospital	Singapore

Sponsors (2)

Lead Sponsor	Collaborator
Singapore General Hospital	Roche Diagnostics

Country where clinical trial is conducted

Singapore, 

References & Publications (4)

Birkeland KI, Bodegard J, Eriksson JW, Norhammar A, Haller H, Linssen GCM, Banerjee A, Thuresson M, Okami S, Garal-Pantaler E, Overbeek J, Mamza JB, Zhang R, Yajima T, Komuro I, Kadowaki T. Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes: A large multinational cohort study. Diabetes Obes Metab. 2020 Sep;22(9):1607-1618. doi: 10.1111/dom.14074. Epub 2020 Jun 3. — View Citation

Hobbs FD, Jukema JW, Da Silva PM, McCormack T, Catapano AL. Barriers to cardiovascular disease risk scoring and primary prevention in Europe. QJM. 2010 Oct;103(10):727-39. doi: 10.1093/qjmed/hcq122. Epub 2010 Aug 4. — View Citation

Malachias MVB, Jhund PS, Claggett BL, Wijkman MO, Bentley-Lewis R, Chaturvedi N, Desai AS, Haffner SM, Parving HH, Prescott MF, Solomon SD, De Zeeuw D, McMurray JJV, Pfeffer MA. NT-proBNP by Itself Predicts Death and Cardiovascular Events in High-Risk Patients With Type 2 Diabetes Mellitus. J Am Heart Assoc. 2020 Oct 20;9(19):e017462. doi: 10.1161/JAHA.120.017462. Epub 2020 Sep 23. — View Citation

Matheus AS, Tannus LR, Cobas RA, Palma CC, Negrato CA, Gomes MB. Impact of diabetes on cardiovascular disease: an update. Int J Hypertens. 2013;2013:653789. doi: 10.1155/2013/653789. Epub 2013 Mar 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of study subjects with reduced left ventricular systolic function	Proportion of study subjects with reduced left ventricular systolic function	Baseline
Other	Proportion of study subjects with reduced left ventricular diastolic function	Proportion of study subjects with reduced left ventricular diastolic function	Baseline
Primary	Number of participants with composite endpoint based on first occurrence of all-cause death or cardiovascular events	Composite endpoint based on the first occurrence of all-cause death or CV events consisting of a composite of non-fatal myocardial infarction, non-fatal stroke, unplanned hospitalisation for heart failure (HHF), coronary revascularisation (PCI or CABG), non-traumatic lower limb amputation, or lower limb arterial revascularisation (surgical or endovascular).	5 years
Secondary	Number of participants with cardiovascular (CV) death	Cardiovascular death consists of death due to acute myocardial infarction, sudden cardiac death, death due to heart failure, stroke, CV procedure, CV hemorrhage or other CV cause.	5 years
Secondary	Number of participants with all-cause death	Death due to any cause.	5 years
Secondary	Number of unplanned hospitalization for heart failure (HHF)	Refers to heart failure event that was a cause of hospitalization (primary or contributing) following baseline visit.	5 years
Secondary	Number of participants with 4-point major adverse cardiovascular event (MACE)	Include CV death, non-fatal myocardial infarction, non-fatal stroke, unplanned HHF	5 years
Secondary	Number of participants with all-cause hospitalization	Include emergency, unplanned or non-elective all-cause hospitalizations	5 years