Vietnamese Rapid Acceleration Protocol for Intensifying Drug Therapy in Heart Failure With Reduced Ejection Fraction (VN-RAPID)

VN-RAPID is an open-label, multicenter, randomized controlled trial evaluating the safety and efficacy of in-hospital initiation and rapid up-titration of four-pillar therapy for hospitalized Asian patients with acute heart failure (AHF) and reduced ejection fraction (HFrEF). The study compares a standardized protocol of intensified treatment (high-intensity care arm) with usual care in patients with elevated NT-proBNP levels who are not on optimal HFrEF medications. The high-intensity care arm involves initiation of all four pillars of HFrEF therapy (RAS inhibitor, beta-blocker, MRA, and SGLT2i) before discharge, followed by a structured 6-week outpatient up-titration process with frequent follow-ups. The study aims for 75% of target doses for RAS inhibitors and beta-blockers, considering the lower blood pressure tendency in Asian populations. Participants will be followed for 180 days to assess clinical outcomes.

Study Overview

• Status: Recruiting
• Conditions: Acute Heart Failure (AHF); Acute Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Other: Usual care; Other: High intensity care

Detailed Description

VN-RAPID is an open-labeled, multicenter, randomized study modeled after the STRONG-HF trial with the aim to evaluate the safety and efficacy of a standardized protocol of in-hospital initiation and rapid up-titration of all four pillars therapy for hospitalized acute heart failure (AHF) Asian patients with reduced ejection fraction (HFrEF). The study will enroll patients hospitalized with AHF with elevated NT-proBNP levels and not receiving optimal doses of oral HFrEF medications within 48 hours of discharge and are hemodynamically stable. These participants will be randomized in a 1:1 ratio to either usual care (named "usual care" arm) or intensification of treatment with all four pillars including RAS inhibitor (either ACEi or ARB or ARNi), beta-blocker, MRA and SGLT2i (named "high intensity care" arm). In the latter arm, the patients will be prescribed all four pillars before discharge with at least ¼ target dose. To ensure patient safety during the outpatient uptitration process, the high intensity care group will undergo thorough assessments at four follow-up appointments over a six-week period post-discharge, including physical examinations for signs and symptoms of congestion, laboratory tests such as NT-proBNP, serum creatinine, electrolytes. In consideration of the generally lower blood pressure observed in Asian populations, VN-RAPID establishes a target dose for RAS inhibitors and beta-blockers at 75% of the conventional target dose during outpatient uptitration. All participants will be followed through 180 days from randomization with 2 additional visits at 90-day and 180-day to assess clinical endpoints.

Primary objective:

To demonstrate that the VN-RAPID protocol-comprising in-hospital initiation and rapid outpatient uptitration of HFrEF four-pillar medical therapy, with lower target doses (75% of conventional) for RAS inhibitors and beta-blockers-is superior to usual care in reducing 180-day all-cause mortality or heart failure rehospitalization among Vietnamese patients hospitalized with acute heart failure and reduced ejection fraction.

Secondary objectives:

• To demonstrate the superiority of the VN-RAPID protocol, compared to usual HFrEF care, in reducing 180-day all-cause mortality
• To demonstrate the superiority of the VN-RAPID protocol, compared to usual HFrEF care, in reducing 180-day heart failure rehospitalization
• To demonstrate the superiority of the VN-RAPID protocol, compared to usual HFrEF care, in reducing 90-day all-cause mortality or heart failure rehospitalization
• To demonstrate the superiority of the VN-RAPID protocol, compared to usual HFrEF care, in reducing left ventricular remodeling by evaluation of LVEDV, LVEF on echocardiography at 90-day and 180-day
• To demonstrate the superiority of the VN-RAPID protocol, compared to usual HFrEF care, in reducing 90-day and 180-day congestion index score
• To evaluate the safety and tolerability of the VN-RAPID protocol

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vu Hoang Vu, Ph.D M.D; Phone Number: +84908431304‬; Email: vu.vh@umc.edu.vn
• Study Contact Backup: Name: Nam Thanh Hai Phan, M.D; Phone Number: +84937728990; Email: nam.pth2@umc.edu.vn

Study Locations

• Vietnam
  • Ho Chi Minh City, Vietnam, 700000
    • Recruiting
    • University Medical Center Ho Chi Minh City
    • Contact: Nam Thanh Hai Phan, M.D; Phone Number: +84937728990; Email: nam.pth2@umc.edu.vn
    • Contact: Vu Hoang Vu, PhD MD; Phone Number: +84‭908431304‬; Email: vu.vh@umc.edu.vn
  • Ho Chi Minh City, Vietnam, 700000
    • Not yet recruiting
    • Thong Nhat HOSPITAL
    • Contact: Tan Van Nguyen, Ph.D M.D; Phone Number: +84903739273‬; Email: nguyenvtan10@ump.edu.vn
  • An Giang
    • Long Xuyen, An Giang, Vietnam, 880000
      • Not yet recruiting
      • An Giang Heart Hospital
      • Contact: Ut Van Be Nguyen, M.D
  • Quang Tri
    • Dong Ha, Quang Tri, Vietnam, 520000
      • Not yet recruiting
      • Quang Tri Province Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual care; Patients will be managed by their cardiologist according to their usual practice. Follow-up appointments will be scheduled as per the cardiologist's instructions. Participants will return to the recruiting study site for clinical outcome assessment by study investigators at 90 and 180 days post-discharge.	Other: Usual care; Patients will be managed by their cardiologist according to their usual practice. Follow-up appointments will be scheduled as per the cardiologist's instructions. Participants will return to the recruiting study site for clinical outcome assessment by study investigators at 90 and 180 days post-discharge.
Experimental: High intensity care; This arm follows a structured algorithm for initiating and uptitrating all four pillars of HFrEF oral medications post-randomization (pre-discharge) and during at least 4 visits over 6 weeks post-discharge.	Other: High intensity care; This arm follows a structured algorithm for initiating and uptitrating all four pillars of HFrEF oral medications post-randomization (pre-discharge) and during at least 4 visits over 6 weeks post-discharge.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
180-day all-cause death or heart failure rehospitalization	Cumulative risk of either rehospitalization for heart failure or death at 180 days	180 days post-discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day all-cause mortality or heart failure rehospitalization	Cumulative risk of either rehospitalization for heart failure or death at 90 days	90 days post-discharge
180-day all-cause mortality	Cumulative risk of death at 180 days	180 days post discharge
180-day heart failure rehospitalization	Cumulative risk of heart failure rehospitalization at 180 days	180 days post discharge
Change in NT-proBNP at 180-day	Change of NT-proBNP levels from pre-discharge to 180 days post-discharge	180 days post-discharge
Change in left ventricular end-diastolic volume at 180-day	Change of left ventricular end-diastolic volume (LVEDV) from pre-discharge to 180 days post-discharge. LVEDV is measured in mL on echocardiography.	180 days post discharge
Change in left ventricular ejection fraction at 180-day	Change of left ventricular ejection fraction (LVEF) from pre-discharge to 180 days post-discharge. LVEF is measured in % on echocardiography using Simpson biplane method.	180 days post discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in congestion score at 180-day	Change of congestion score from pre discharge to 180 days post discharge. The congestion score was calculated as a sum of points gained for: Presence (1 point)/absence (0 points) of edema; Presence (1 point)/absence (0 points) of pulmonary rales; JVP lower than 6 cm (0 points)/equal to or greater than 6 cm (1 point) A congestion score of 0 was defined as a criterion for successful decongestion.	180 days post discharge
Change on lung ultrasound at 180-day	Change of the number of B lines measured at pre discharge to 180 days post discharge. B lines are measured on lung ultrasound using a 4-zone scanning protocol. 0 B line indicates no congestion.	180 days post discharge

Collaborators and Investigators

• Sponsor: University Medical Center Ho Chi Minh City (UMC)
• Collaborators: University of Medicine and Pharmacy at Ho Chi Minh City; INSERM UMR-942, Paris, France; Momentum Research, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: September 8, 2024
• First Submitted That Met QC Criteria: September 10, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 31, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Acute heart failure; HFrEF; STRONG-HF; Rapid uptitration
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: DHYD-VNRAPID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No