Vietnamese rapid protocol to speed up the four main heart-failure medicines for people with reduced ejection fraction

Vietnamese Rapid Acceleration Protocol for Intensifying Drug Therapy in Heart Failure With Reduced Ejection Fraction

This program tests whether starting and quickly increasing the four key heart-failure medicines before discharge and during early outpatient follow-up helps adults hospitalized with reduced ejection fraction and high NT‑proBNP.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 500 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: University Medical Center Ho Chi Minh City (UMC) (Academic / other)
• Locations: 4 sites (Long Xuyen, An Giang and 3 other locations)
• Trial ID: NCT06595290 on ClinicalTrials.gov

What this trial studies

VN-RAPID is an open-label, multicenter, randomized 1:1 trial comparing a standardized intensified-treatment protocol with usual care in hospitalized Asian patients with acute HFrEF and elevated NT‑proBNP. The intensified arm starts all four guideline HFrEF drug classes (RAS inhibitor, beta-blocker, MRA, SGLT2i) before discharge at a minimum dose and follows a structured six-week outpatient uptitration with four close follow-up visits including exams and labs. Dose targets for RAS inhibitors and beta-blockers are set at 75% of conventional targets to account for lower baseline blood pressure in many Asian patients. Participants are followed for 180 days for clinical outcomes including readmissions and mortality.

Who should consider this trial

Good fit: Adults hospitalized with acute HFrEF (LVEF ≤40%), elevated NT‑proBNP, hemodynamically stable, not on optimal HFrEF therapy, and meeting BP (>90 mmHg), heart rate (≥60 bpm), and potassium (≤5.0 mmol/L) criteria are ideal candidates.

Not a fit: Patients with preserved ejection fraction, unstable blood pressure or heart rate, significant renal dysfunction or hyperkalemia, or those already receiving optimized HFrEF therapy are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could reduce early hospital readmissions and deaths and improve symptoms by getting patients on effective medicine doses sooner.

How similar studies have performed: The protocol is modeled after the STRONG-HF approach, which demonstrated benefits from rapid initiation and uptitration of guideline therapies in a non-Asian population.

Eligibility criteria

Inclusion Criteria:

1. Hospital admission with diagnosis of acute heart failure assessed by clinical signs and symptoms of congestion and radiographic, biological tests (if admitted with acute coronary syndrome, required at least Killip class II or clear evidence of congestion on admission assessed by chest x-ray or lung ultrasound and/or pulmonary congestion requiring intravenous treatment)
2. Female or male patients ≥ 18 years old
3. At randomization:

   1. Systolic blood pressure \> 90 mmHg (at least 2 measurements on 2 different occasions) and
   2. Heart rate ≥ 60 bpm (at least 2 measurements on 2 different occasions) and
   3. Serum potassium ≤ 5.0 mmol/L
4. Left ventricular ejection fraction (LVEF) ≤ 40% assessed locally by Simpson's Biplane method via echocardiography (if multiple LVEF measurements, the last one performed prior to randomization should be considered as the qualifying measurement)
5. Persistent congestion at the time of randomization with pre-discharge NT-proBNP ≥ 1500 ng/L
6. HFrEF medications at randomization:

   1. ≤ ¼ RASi/ARNi target dose and
   2. ≤ ¼ beta-blocker target dose and
   3. ≤ ½ MRA dose
7. Obtained written informed consent form

Exclusion Criteria:

1. Clearly documented intolerance to high doses of RASi/ARNi or beta-blockers
2. Absolute contraindication to usage of RASi/ARNi or beta-blocker or MRA or SGLT2i as per ESC 2021/ACC 2022 Heart failure guideline
3. LVEF \>40% assessed by echocardiography on the latest measurement prior to discharge
4. Renal disease or eGFR \< 30 mL/min/1.73m2 (as estimated by the CKD-EPI 2021 or the simplified MDRD) at Screening or history of dialysis.
5. Significant pulmonary disease contributing substantially to the patients' dyspnea such as FEV1\< 1 liter or need for chronic systemic or nonsystemic steroid therapy, or any kind of primary right heart failure such as primary pulmonary hypertension or recurrent pulmonary embolism.
6. Implantation of cardiac resynchronization device or underwent coronary artery bypass graft surgery within 3 months
7. Myocardial infarction, unstable angina or cardiac surgery within 3 months, or cardiac resynchronization therapy (CRT) device implantation within 3 months, or percutaneous coronary intervention (PCI), within 1 month prior to Screening.
8. AHF triggered primarily by a correctable etiology such as significant arrhythmia (e.g., sustained ventricular tachycardia, or atrial fibrillation/flutter with sustained ventricular response \>130 beats per minute, or bradycardia with sustained ventricular arrhythmia \<45 beats per minute), infection, severe anemia, pulmonary embolism, exacerbation of COPD, planned admission for device implantation or severe non-adherence leading to very significant fluid accumulation prior to admission and brisk diuresis after admission. Troponin elevations without other evidence of an acute coronary syndrome are not an exclusion.
9. Uncorrected thyroid disease, active myocarditis, or known amyloid or hypertrophic obstructive cardiomyopathy.
10. History of heart transplant or on a transplant list, or using or planned to be implanted with a ventricular assist device.
11. Sustained ventricular arrhythmia with syncopal episodes within the 3 months prior to screening that is untreated.
12. Presence at Screening of any hemodynamically significant valvular stenosis or regurgitation, except mitral or tricuspid regurgitation secondary to left ventricular dilatation, or the presence of any hemodynamically significant obstructive lesion of the left ventricular outflow tract.
13. Active infection at any time during the AHF hospitalization prior to Randomization based on abnormal temperature and elevated WBC or need for intravenous antibiotics.
14. Stroke or TIA within the 3 months prior to Screening.
15. Primary liver disease considered to be life threatening.
16. Psychiatric or neurological disorder, cirrhosis, or active malignancy leading to a life expectancy \< 6 months.
17. Prior (defined as less than 30 days from screening) or current enrollment in a CHF trial or participation in an investigational drug or device study within the 30 days prior to screening
18. Discharge for the AHF hospitalization anticipated to be \> 14 days from admission, or to a long-term care facility. Randomization must occur within 12 days following admission and at within 2 days prior to anticipated discharge.
19. Inability to comply with all study requirements, due to major comorbidities, social or financial issues, or a history of noncompliance with medical regimens, that might compromise the patient's ability to understand and/or comply with the protocol instructions or follow-up procedures
20. Pregnant or nursing (lactating) women.

Where this trial is running

Long Xuyen, An Giang and 3 other locations

• An Giang Heart Hospital — Long Xuyen, An Giang, Vietnam (Not_yet_recruiting)
• Thong Nhat Hospital — Ho Chi Minh City, Ho Chi Minh City, Vietnam (Not_yet_recruiting)
• University Medical Center Ho Chi Minh City — Ho Chi Minh City, Ho Chi Minh City, Vietnam (Recruiting)
• Quang Tri Province Hospital — Đông Hà, Quang Tri, Vietnam (Not_yet_recruiting)

Study contacts

• Study coordinator: Vu Hoang Vu, Ph.D M.D

Conditions Acute Heart Failure; Acute Heart Failure With Reduced Ejection Fraction; HFrEF; STRONG-HF; Acute heart failure; Rapid uptitration