Clinical Outcomes of Levosimendan Versus Dobutamine Versus Milrinone in Cases With Acute Decompensated Heart Failure With Impaired Renal Function

This study aimed to assess and compare the cardiac, renal, and clinical efficacy of Levosimendan (LEV), Dobutamine (DOB), and milrinone (MIL) in cases with acute decompensated heart failure (ADHF) complicated by renal impairment, with a focus on their role in the management of cardiorenal syndrome (CRS).

Study Overview

• Status: Completed
• Conditions: Acute Decompensated Heart Failure (ADHF); Cardiorenal Syndrome (CRS)
• Intervention / Treatment: Drug: Levosimendan; Drug: Dobutamine; Drug: Milrinone

Detailed Description

Methods Upon ICU admission and once the clinical decision to initiate inotropic therapy was made, all enrolled patients underwent a standardized evaluation protocol that included: Comprehensive medical history and clinical examination. Laboratory assessments, including Complete blood count (CBC), Arterial blood gases (ABG), Liver and kidney function tests, Serum electrolytes, Random blood glucose, Estimated glomerular filtration rate (eGFR). Cardiac parameters were recorded by EV1000 clinical platform device to assess the cardiac index (CI), stroke volume variations (SVV), and systemic vascular resistance index (SVRI). at baseline, 24 hours after inotropic therapy initiation, and again on day 7 or prior to ICU discharge whichever occurred first. Renal function indicators _including serum creatinine, blood urea nitrogen (BUN), eGFR, and urinary output_ were measured before the start of infusion and monitored daily until ICU discharge or death.

Medications were routinely administered as part of standard institutional practice. Where trial-specific medications were used, we have provided a clear distinction between these and routine medications. omission of medications not routinely used in our protocol did not cause harm to patients, and all treatments provided were in accordance with current safety standards and ethical guidelines.

Inotropic agents titrated to response to keep mean arterial blood pressure above 55 mmHg :

• Levosimendan: loading dose 6-12 microgram/ kg then continuous infusion of 0.05-0.2 µg/kg/min.
• Dobutamine: continuous infusion starting at 2.5 µg/kg/min, titrated up to 20 µg/kg/min as needed.
• Milrinone: 50 mcg/kg loading dose, then 0.375-0.75 mcg/kg/min IV according to patient response.

Primary outcomes included changes in cardiac and renal function parameters. Pre- and post-infusion values were compared to assess treatment response.

Secondary outcomes encompassed length of ICU stay, total hospital stay, ICU readmission, and all-cause in-hospital mortality.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Faculty of Medicine Ain Shams University

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Adult (>18 years old) patients with ADHF (LVEF ≤ 40% documented prior to enrollment) admitted to the ICU with renal impairment (estimated GFR between 30 and 60 mL/min/1.73 m², calculated using the Modification of Diet in Renal Disease Study equation (MDRD equation) [10] and require inotropic support.

Description

Inclusion Criteria:

• Adult (>18 years old) patients with ADHF (LVEF ≤ 40% documented prior to enrollment) admitted to the ICU with renal impairment (estimated GFR between 30 and 60 mL/min/1.73 m², calculated using the Modification of Diet in Renal Disease Study equation (MDRD equation)) and require inotropic support.

Exclusion Criteria:

Cases were excluded from the study if they met any of the following criteria:

• Age younger than 18 years
• Untreated acute HF
• Resting heart rate exceeding 120 beats per minute
• Recent MI or acute coronary syndrome within the previous two months
• Diagnosed pulmonary embolism
• Structural cardiac conditions
• Known history of kidney disease diagnosed prior to HF
• Administration of contrast agents or nephrotoxic drugs within the previous seven days
• Severe liver dysfunction (Child C)
• Active acute inflammatory or infectious diseases.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Levosimendan group	Drug: Levosimendan; Inotropic agents titrated to response to keep mean arterial blood pressure above 55 mmHg : •Levosimendan: loading dose 6-12 microgram/ kg then continuous infusion of 0.05-0.2 µg/kg/min.
Dobutamine group	Drug: Dobutamine; Inotropic agents titrated to response to keep mean arterial blood pressure above 55 mmHg : • Dobutamine: continuous infusion starting at 2.5 µg/kg/min, titrated up to 20 µg/kg/min as needed.
Milrinone group	Drug: Milrinone; Inotropic agents titrated to response to keep mean arterial blood pressure above 55 mmHg : • Milrinone: 50 mcg/kg loading dose, then 0.375-0.75 mcg/kg/min IV according to patient response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
renal function parameters.	Changes in serum creatinine (mg/dl). Pre- and post-infusion values were compared to assess treatment response.	7 days
renal function	Changes in serum BUN (mg/dl). Pre- and post-infusion values were compared to assess treatment response.	7 days
renal function	Changes in eGFR (mL/min/1.73 m²). Pre- and post-infusion values were compared to assess treatment response.	7 days
renal function	Changes in urine output (mL/day). Pre- and post-infusion values were compared to assess treatment response.	7 days
cardiac function	changes in ejection fraction % by transthoracic echocardiography. Pre- and post-infusion values were compared to assess treatment response.	7 days
cardiac function	Changes in cardiac index (L/min/m²) measured by EV1000 clinical platform device. Pre- and post-infusion values were compared to assess treatment response.	7 days
cardiac function	changes in stroke volume variations (SVV) measured by EV1000 clinical platform. Pre- and post-infusion values were compared to assess treatment response.	7 days
cardiac function	changes in systemic vascular resistance index (SVRI) using EV1000 clinical platform device. Pre- and post-infusion values were compared to assess treatment response.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
morbidity	length of ICU stay (days).	28 day
morbidity	Total hospital stay (days)	28 day
morbidity	ICU readmission	28 day
mortality	In-hospital mortality.	28 day

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): June 1, 2024
• Study Completion (Actual): June 1, 2024

Study Registration Dates

• First Submitted: September 10, 2025
• First Submitted That Met QC Criteria: September 15, 2025
• First Posted (Actual): September 22, 2025

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Levosimendan; Milrinone; dobutamine; Acute Decompensated Heart Failure (ADHF); Cardiorenal Syndrome (CRS)
• Additional Relevant MeSH Terms: Urogenital Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Renal Insufficiency; Heart Failure; Cardio-Renal Syndrome; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Catechols; Phenols; Benzene Derivatives; Phenethylamines; Ethylamines; Aminopyridines; Catecholamines; Amrinone; Hydrazines; Hydrazones; Pyridazines; Simendan; Milrinone; Dobutamine
• Other Study ID Numbers: FMASU MD 185a/2022/2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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