Study on Starting Valsartan, Sacubitril, and Empagliflozin for Patients with Heart Failure with Reduced Ejection Fraction

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What is this study about?

This clinical trial is focused on studying treatments for heart failure with reduced ejection fraction, a condition where the heart muscle does not pump blood as well as it should. The study will use two types of medications: Entresto and Jardiance. Entresto contains two active substances, valsartan and sacubitril (also known as AHU377), and is used to help the heart work better. Jardiance contains empagliflozin, which helps the body remove excess sugar through urine and can also benefit heart health. Another medication being studied is Forxiga, which contains dapagliflozin and works similarly to Jardiance.

The purpose of the study is to compare the safety of two different ways to start these treatments. One method involves starting both Entresto and Jardiance at the same time, while the other method involves starting Jardiance first and adding Entresto later. Participants will be randomly assigned to one of these two groups. The study will last for about six months, during which participants will be monitored for any side effects or changes in their condition.

Throughout the study, researchers will keep track of various health indicators, such as blood pressure, kidney function, and heart health. They will also monitor for any serious events like hospitalization due to heart failure or changes in medication needs. The goal is to determine which treatment approach is safer and more effective for managing heart failure with reduced ejection fraction.

1 initial visit

Upon joining the study, an initial visit is conducted. During this visit, eligibility is confirmed based on specific criteria such as age, heart failure symptoms, and blood pressure levels.

A blood test is performed to check kidney function and potassium levels. If female, a pregnancy test is conducted if applicable.

2 randomization

Participants are randomly assigned to one of two groups. One group will start taking both Entresto and Jardiance or Forxiga at the same time, while the other group will start with Jardiance or Forxiga first, followed by Entresto between weeks 4 and 12.

3 medication administration

For those starting both medications simultaneously, Entresto is taken orally in doses of 24 mg/26 mg, 49 mg/51 mg, or 97 mg/103 mg, twice daily. Jardiance or Forxiga is taken orally at a dose of 10 mg once daily.

For those starting sequentially, Jardiance or Forxiga is taken first at a dose of 10 mg once daily. Entresto is added later, with the same dosing options as the simultaneous group.

4 follow-up visits

Regular follow-up visits are scheduled to monitor health and adjust medication dosages if necessary. These visits include checking blood pressure, kidney function, and potassium levels.

Participants are observed for any side effects such as low blood pressure, changes in kidney function, or electrolyte imbalances.

5 end of study

The study concludes after a follow-up period of 6 months. Final assessments are conducted to evaluate the safety and effectiveness of the medication initiation strategies.

Participants are provided with information about their health status and any necessary follow-up care.

Who Can Join the Study?

Must be 18 years or older.
Must have symptoms of heart failure that are classified as NYHA class II, III, or IV. (NYHA is a way to classify the severity of heart failure symptoms.)
Must have a left ventricle ejection fraction of 49% or less. (This is a measure of how well the heart is pumping blood, assessed by an ultrasound of the heart called a transthoracic echocardiogram.)
Must have a glomerular filtration rate of 25 ml/min/1.73m² or higher. (This is a measure of kidney function.)
Must have a serum potassium level of 5.4 mmol/L or less. (Potassium is a mineral in the blood that needs to be at a certain level for the heart to function properly.)
Must have a systolic blood pressure of 100 mmHg or higher. (Systolic blood pressure is the top number in a blood pressure reading, indicating the pressure in the arteries when the heart beats.)
Must not have been treated with ARNi or SGLT2i medications in the past month, except if started 5 days before joining the study. (ARNi and SGLT2i are types of medications used to treat heart failure.)
If female and not able to have children, must meet specific criteria detailed in the full protocol.
If female and able to have children, must have a negative pregnancy test at the start of the study and agree to use one highly effective method of birth control as detailed in the full protocol.

Who Cannot Join the Study?

Patients with a history of severe allergic reactions to the study medications cannot participate.
Patients who are currently pregnant or breastfeeding are not eligible.
Individuals with severe kidney disease, which means their kidneys are not working well, are excluded.
Patients with severe liver disease, meaning their liver is not functioning properly, cannot join the study.
Anyone who has had a heart attack in the last 3 months is not eligible.
Patients with uncontrolled high blood pressure, which means their blood pressure is too high despite treatment, are excluded.
Individuals with a history of drug or alcohol abuse in the past year cannot participate.
Patients who are currently participating in another clinical trial are not eligible.
Anyone with a serious mental health condition that might affect their ability to follow the study procedures is excluded.
Patients with any other medical condition that the study doctors think would make it unsafe for them to participate are not eligible.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Centro Hospitalar Universitario Sao Joao E.P.E.	Porto	Portugal

Other Sites

Site Name	City	Country
Unidade Local De Saude De Gaia/Espinho E.P.E.	Vila Nova De Gaia	Portugal
Hospital Pedro Hispano	Matosinhos	Portugal
Cekkvp Hrfgzoomtj Uqtwqjqgfqvax Dm Pqbhy Ecfbae	Porto	Portugal

Trial status

Country	Status	Recruitment Start
Portugal	Not recruiting	01.05.2023

Trial locations

Investigated drugs:

Angiotensin Receptor-Neprilysin Inhibitor (ARNi) is a type of medication used to treat heart failure. It works by blocking certain enzymes in the body that can cause blood vessels to tighten. By doing this, it helps to relax the blood vessels, making it easier for the heart to pump blood. This can help improve symptoms of heart failure and reduce the risk of hospitalization.

Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) is a medication that helps manage heart failure by affecting how the kidneys process sugar. It works by preventing the kidneys from reabsorbing sugar back into the blood, which helps lower blood sugar levels. This can also lead to a reduction in the amount of fluid in the body, which can help ease the workload on the heart and improve heart failure symptoms.

Heart failure with reduced ejection fraction – Heart failure with reduced ejection fraction (HFrEF) is a condition where the heart muscle is weakened and cannot pump blood efficiently. This leads to a decrease in the amount of blood ejected from the heart with each beat. Over time, the heart’s ability to supply the body with adequate blood diminishes, causing symptoms like fatigue, shortness of breath, and fluid retention. As the condition progresses, the heart may become enlarged, and the walls of the heart chambers may thicken. This can result in further reduction of the heart’s pumping ability and worsening of symptoms. The progression of HFrEF can lead to increased hospitalizations and a decline in quality of life.

Trial ID:

2022-502409-14-00

Protocol code:

INITIATE-HFrEF

NCT ID:

NCT05989503

Trial Phase:

Human Pharmacology (Phase I) – Other

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Study on Starting Valsartan, Sacubitril, and Empagliflozin for Patients with Heart Failure with Reduced Ejection Fraction

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?