Dapa Acute Heart Failure Study

Heart Failure Clinical Trial

Official title:

The Effect of Early Inpatient Initiation of Dapagliflozin on the Health-related Quality of Life of Patients With Heart Failure With All Range of Ejection Fraction: a Local Registry

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05759000
• Other study ID #: 2022.501
• Status: Recruiting
• Start date: April 9, 2023
• Est. completion date: December 9, 2025

Study information

• Verified date: February 2024
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Heart failure (HF) is one of the most important reasons for hospital admission and is associated with high mortality and morbidity. After discharge, up to 40% of patients are readmitted within 6 months and 1-year post-discharge mortality is high. The cost burden of treating patients with HF is high and ~80% of healthcare costs are related to hospital admissions.

Sodium-glucose cotransporter-2 (SGLT2) inhibitor is considered one of the four foundational therapies (ACE-I or ARNI, beta-blockers, MRA, and SGLT2 inhibitors) for HFrEF.

This is an investigator-initiated, prospective, single-centre, registry that evaluates the change in HRQL as measured by the KCCQ-TSS after the initiation of Dapagliflozin.

Description:

Heart failure (HF) is one of the most important reasons for hospital admission and is associated with high mortality and morbidity and poor quality of life (1). After discharge, up to 40% of patients are readmitted within 6 months and 1-year post-discharge mortality is high (2-4). The cost burden of treating patients with HF is high and ~80% of healthcare costs are related to hospital admissions (5).

Sodium-glucose cotransporter-2 (SGLT2) inhibitor is considered one of the four foundational therapies (ACE-I or ARNI, beta-blockers, MRA, and SGLT2 inhibitors) for HFrEF (6) However, guidelines do not specify the sequence and the timing of which therapy to be commenced. In particular, dapagliflozin has been shown in randomized controlled trials to reduce the combined risk of cardiovascular death or HF hospitalization and improve quality of life in HF patients with both reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), respectively, regardless of the presence or absence of diabetes in the DAPA-HF and PRESERVED-HF trials (7, 8).

HF patient usually has poor QoL, and health-related quality of life (HRQL) measure has been shown to be associated with all cause death and HF hospitalization in a multinational study (9). There exist a geographical and ethnical variation in patients HRQL and clinical outcomes amongst various countries (9). The Kansas City Cardiomyopathy Questionnaire-total symptom scores (KCCQ-TSS) is a simple, widely available, and inexpensive tool that characterizes a patient's HF-related health status. Showing that it can be used as a marker to predict major clinical outcomes in a wide spectrum of patients with HF across the world would confirm its usefulness in research as well as in clinical practice.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 9, 2025
• Est. primary completion date: September 9, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. Subject age >18 hospitalized for primary diagnosis of acute HF

2. Dyspnoea (exertional or at rest) and 1 of the following signs:

• Congestion on chest X-ray

• Rales on chest auscultation

• Clinically relevant oedema (e.g. =1+ on a 0 to 3+ scale)

• Elevated jugular venous pressure

3. NT-proBNP =300 ng/L (If ongoing atrial fibrillation/flutter at recruitment, NT-pro BNP must be = 600 pg/mL.4. 5).

Exclusion Criteria:

1. Cardiogenic shock

2. Current hospitalization for acute HF primarily triggered by pulmonary embolism or cerebrovascular accident.

3. Interventions in the past 30 days prior or planned during the study: Major cardiac surgery, or TAVI, or PCI, or MitraClip

4. Current or expected heart transplant, LVAD, on IABP or other forms of mechanical support.

5. Haemodynamically severe uncorrected primary cardiac valvular disease planned for surgery or intervention during the course of the study.

6. eGFR <20 mL/min/1.73m2 as measured during index hospitalization (latest measurement before randomization) or patients requiring dialysis

7. Type 1 diabetes mellitus

8. History of ketoacidosis, including diabetic ketoacidosis

9. Prior treatment with SGLT2 inhibitors in 90 days prior to current admission.

10. Documented severe allergy or intolerance to SGLT2 inhibitors.

11. Pregnant subjects

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Dapagliflozin
Sodium-glucose cotransporter-2 (SGLT2) inhibitor is considered one of the four foundational therapies (ACE-I or ARNI, beta-blockers, MRA, and SGLT2 inhibitors) for HFrEF (6). However, guidelines do not specify the sequence and the timing of which therapy to be commenced. In particular, dapagliflozin has been shown in randomized controlled trials to reduce the combined risk of cardiovascular death or HF hospitalization and improve quality of life in HF patients with both reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), respectively, regardless of the presence or absence of diabetes in the DAPA-HF and DELIVER trials (

Locations

Country	Name	City	State
Hong Kong	The Chinese University of Hong Kong	Shatin

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (9)

Braunschweig F, Cowie MR, Auricchio A. What are the costs of heart failure? Europace. 2011 May;13 Suppl 2:ii13-7. doi: 10.1093/europace/eur081. — View Citation

Chun S, Tu JV, Wijeysundera HC, Austin PC, Wang X, Levy D, Lee DS. Lifetime analysis of hospitalizations and survival of patients newly admitted with heart failure. Circ Heart Fail. 2012 Jul 1;5(4):414-21. doi: 10.1161/CIRCHEARTFAILURE.111.964791. Epub 20 — View Citation

Heidenreich PA, Albert NM, Allen LA, Bluemke DA, Butler J, Fonarow GC, Ikonomidis JS, Khavjou O, Konstam MA, Maddox TM, Nichol G, Pham M, Pina IL, Trogdon JG; American Heart Association Advocacy Coordinating Committee; Council on Arteriosclerosis, Thrombo — View Citation

Johansson I, Joseph P, Balasubramanian K, McMurray JJV, Lund LH, Ezekowitz JA, Kamath D, Alhabib K, Bayes-Genis A, Budaj A, Dans ALL, Dzudie A, Probstfield JL, Fox KAA, Karaye KM, Makubi A, Fukakusa B, Teo K, Temizhan A, Wittlinger T, Maggioni AP, Lanas F — View Citation

Joynt KE, Jha AK. Who has higher readmission rates for heart failure, and why? Implications for efforts to improve care using financial incentives. Circ Cardiovasc Qual Outcomes. 2011 Jan 1;4(1):53-9. doi: 10.1161/CIRCOUTCOMES.110.950964. Epub 2010 Dec 14 — View Citation

Krumholz HM, Merrill AR, Schone EM, Schreiner GC, Chen J, Bradley EH, Wang Y, Wang Y, Lin Z, Straube BM, Rapp MT, Normand SL, Drye EE. Patterns of hospital performance in acute myocardial infarction and heart failure 30-day mortality and readmission. Circ — View Citation

McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman C — View Citation

Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CSP, Martinez F, Shah SJ, Desai AS, Jhund PS, Belohlavek J, Chiang CE, Borleffs CJW, Comin-Colet J, Dobreanu D, Drozdz J, Fang JC, Alcocer-Gamba MA, A — View Citation

Writing Committee; Maddox TM, Januzzi JL Jr, Allen LA, Breathett K, Butler J, Davis LL, Fonarow GC, Ibrahim NE, Lindenfeld J, Masoudi FA, Motiwala SR, Oliveros E, Patterson JH, Walsh MN, Wasserman A, Yancy CW, Youmans QR. 2021 Update to the 2017 ACC Exper — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in KCCQ-TSS		Change from baseline in KCCQ-TSS after 90 days of treatment.
Secondary	Change from baseline in log-transformed NT-proBNP level		Change from baseline in log-transformed NT-proBNP level over 90 days of treatment
Secondary	Change in NYHA class		Change in NYHA class over 90 days of treatment
Secondary	Days alive and out of hospital from study drug initiation		90 days
Secondary	Days alive and out of hospital from study drug initiation		Days alive and out of hospital from study drug initiation until 90 days after randomization
Secondary	Time to first occurrence of cardiovascular death or heart Dapa AHF study Ver. 1.4 dated 7Oct2022 2 failure event		90 days
Secondary	Occurrence of HHF		Occurrence of HHF until 90 days after initial hospital discharge
Secondary	Occurrence of Sustained eGFR reduction of =40% eGFR, or - Sustained eGFR <15mL/min/1.73m2 for patients with baseline eGFR =30 mL/min/1.73m2 - Sustained eGFR <10mL/min/1.73m2 for patients with baseline eGFR <30 mL/min/1.73m2.		Occurrence of Sustained eGFR until 90 days after initial hospital discharge
Secondary	Change from baseline in 6MWD		Change from baseline in 6MWD at 90 days
Secondary	Cost effectiveness of early initiation of dapagliflozin for heart failure events avoided		90 days
Secondary	Clinical benefit	a composite of all-cause mortality, number of heart failure events (including hospitalization for HFs, urgent heart failure visits and unplanned outpatient visits)	90 days
Secondary	quality-of-life years (QALY) gained of dapagliflozin for heart failure events avoided		90 days