Levosimendan in Acute Decompensated Heart Failure

NCT07262723 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 59.127.1557.013.19.PG.2025.364
• Study Type: interventional
• Target: 332
• Locations: 1 country
• Sites: 6

Brief Summary

Acute decompensated heart failure (ADHF) is one of the major causes of hospitalization and mortality worldwide. Despite advances in medical treatments, managing ADHF remains complex, especially in high-risk populations. Levosimendan, a calcium sensitizer that improves myocardial contractility and reduces complications associated with acute decompensated heart failure, has shown potential in improving outcomes in these patients. The present study aims to evaluate the efficacy and safety of levosimendan in patients with ADHF in a real-world clinical setting. This pragmatic, multicenter, randomized, controlled trial will include adult patients diagnosed with ADHF in two groups: one receiving levosimendan infusion, and the other receiving standard care for heart failure management, according to the most up-to-date clinical protocols. The study is designed to assess both the efficacy and safety of levosimendan, comparing it with the current standard of care. The primary endpoint of the study will be a clinical composite outcome measured from the NYHA functional classification of heart failure and patient global assessment. Secondary endpoints will include change in serum pro-BNP levels, clinical outcome of heart failure, changes in dyspnea status, all-cause and cardiac mortality. Safety endpoints, including adverse events, will also be systematically recorded and analyzed. Adverse events will be closely monitored, categorized as either mild, moderate, or severe, and their potential association with the treatment will be assessed. Data collection will occur at baseline and during subsequent follow-up visits at 6 hours, 24 hours, 5 days (or day of discharge), and 90 days post-treatment. Key efficacy measures will be obtained through clinical evaluations and laboratory tests, including blood pressure, electrocardiogram (ECG) findings, and NT-proBNP serum levels. The statistical analysis will follow an intention-to-treat (ITT) and Per protocol (PP) approach to account for all enrolled patients, ensuring robust and generalizable findings. This study will be conducted in accordance with Good Clinical Practice (GCP) guidelines and ethical standards outlined in the Declaration of Helsinki, prioritizing participant safety and scientific rigor throughout the study. 12 The results of this trial will provide critical insights into the potential benefits of levosimendan for treating ADHF, and could potentially inform clinical decision-making, offering a more effective therapeutic option in managing this life-threatening condition.

Conditions

Acute Decompensated Heart Failure (ADHF)

Keywords

Acute decompensated heart failure (ADHF); Levosimendan; Real-world evidence; Efficacy; Safety; NT-proBNP / pro-BNP levels; Randomized controlled trial (RCT); Electrocardiogram (ECG); Good Clinical Practice (GCP); Declaration of Helsinki; Adverse events

Outcome Measures

Primary Outcomes (1)

• Clinical Improvement in Heart Failure Symptoms

  Improvement in heart failure symptoms during the first five days of treatment, categorized as improved (moderate or marked improvement at 6 hours, 24 hours, and 5 days without deterioration), unchanged (neither improved nor worsened), or worse (persistent unresponsive symptoms after 24 hours, need for rescue intervention, or moderate/marked worsening).

  From baseline to 5 days after treatment initiation

Secondary Outcomes (3)

• Safety Outcomes - Adverse Events and Serious Adverse Events

  From baseline to 90 days follow-up

• Changes in Clinical and Functional Status

  From baseline to 90 days follow-up

• Hospitalization and Mortality Outcomes

  During index hospitalization and up to 90 days post-treatment initiation

Study Arms (2)

Intervention Arm

EXPERIMENTAL

Participants will receive standard guideline-directed care for heart failure plus levosimendan infusion. Levosimendan will be administered as a continuous intravenous infusion at 0.1 μg/kg/min for 24 hours, in addition to standard therapy.

Drug: Levosimendan

Standard Care

ACTIVE COMPARATOR

Participants will receive standard guideline-directed care for heart failure according to the 2024 ACC guidelines. This may include diuretics, vasodilators, inotropes, and other evidence-based therapies as clinically indicated.

Other: Standard care

Interventions

Levosimendan DRUG

Levosimendan is a calcium-sensitizing inotrope with vasodilatory effects, enhancing heart contractility without raising oxygen demand and promoting vascular relaxation. In this trial, patients will be randomized to receive either standard care alone or standard care plus levosimendan (0.1 μg/kg/min IV infusion for 24 hours).

Intervention Arm

Standard care OTHER

Participants will receive standard care for acute decompensated heart failure according to the 2024 ACC Guideline for the Management of Heart Failure. This may include intravenous diuretics, vasodilators, inotropes, renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors as clinically indicated.

Standard Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (age \>18 years)
• Both male and female sex
• Having left ventricular dysfunction, evidenced by a left ventricular ejection fraction \<40% within the prior 12 months
• Hospitalized for the treatment of ADHF
• Remained dyspneic at rest despite treatment with intravenous diuretics (NYHA class IV)
• Patients might have received intravenous vasodilators and/or positive inotropic drugs (except amrinone and milrinone), but the infusion rates of these drugs must have remained constant for at least 2 h before entry into the study.

You may not qualify if:

• History of invasive cardiac procedure
• Cardiac surgery during lifetime within 3 months prior to screening
• Cardiac revascularization within 3 months prior to screening
• Left ventricular assist device (LVAD) implantation within 3 months prior to screening
• A cardioversion within 4 h prior to screening, or
• Cardiac re-synchronization procedure within 30 days prior to screening)
• Rhythm disorders (e.g. earlier Torsades de Pointes, increased heart rate)
• Severe ventricular outflow obstruction
• Angina within 6 h prior to screening
• Hypotension (a systolic blood pressure \<90 mmHg) \[Can be included after resuscitation, when SBP will be \>90 mmHg by noradrenaline infusion\]
• Uncorrected hypokalemia
• CNS disease (e.g. stroke, TIA)
• Respiratory (e.g. COPD exacerbation requiring systematic steroids or intubation)
• Renal insufficiency (e.g. increased serum creatinine clearance rate \<15 mL/min)
• Hepatic impairment (e.g. significant increase in liver enzymes, \>5x the upper limit of normal)

Sponsors & Collaborators

• Pi Research and Development Center, Bangladesh: collaborator
• Chittagong Medical College: lead
• Beacon Pharmaceuticals PLC: collaborator

Study Sites (6)

Chittagong Medical College Hospital, Chattogram

Chittagong, 4000, Bangladesh

Location

Chattogram Maa-O-Shishu Hospital Medical College Hospital

Chittagong, 4100, Bangladesh

Location

Apollo Imperial Hospital & Max Hospital

Chittagong, 4202, Bangladesh

Location

Cox's Bazar Medical College

Cox’s Bāzār, 4700, Bangladesh

Location

National Institute of Cardiovascular Diseases

Dhaka, 1207, Bangladesh

Location

United Hospital Limited

Dhaka, 1212, Bangladesh

Location

MeSH Terms

Interventions

Simendan; Standard of Care

Intervention Hierarchy (Ancestors)

Hydrazones; Hydrazines; Organic Chemicals; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Mohammad Jahid Hasan, MBBS, MPH

CONTACT

8801767818973; dr.jahid61@gmail.com

Tamanna Tabassum, MBBS, MPH

CONTACT

+8801755383138; dr.tabassum1991@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Cardiology

Model Details: This study uses a parallel assignment interventional model. Adults with acute decompensated heart failure will be randomized by computer-generated block randomization (block size six) into two groups. The experimental arm will receive standard guideline-directed care plus levosimendan infusion (0.1 μg/kg/min for 24 hours), while the control arm will receive standard care alone following the 2024 ACC guidelines. The trial is open-label, with both investigators and participants aware of treatment assignments. The primary purpose is treatment, evaluating the efficacy and safety of levosimendan in real-world clinical practice. A total of 332 patients (166 per arm) will be enrolled and followed for 90 days, with assessments at baseline, 6h, 24h, 5 days (or discharge), and 90 days.

Study Record Dates

• First Submitted: November 23, 2025
• First Posted: December 4, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: December 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

BA (6)