AMBulatory UltraSound for Heart Failure Management

Study Overview
=================
Brief Summary
-----------------
AMBUSH study is a multicenter randomized, controlled, open-label clinical trial (PROBE (Prospective Randomized Open Blinded End-point) type). The main objective of AMBUSH study is to assess the effect of therapeutic management guided by pulmonary ultrasound and the assessment of the inferior vena cava in patients with heart failure seen in an ambulatory (outpatient) setting on a mixed clinical-biological endpoint (including variations of natriuretic peptides - NtProBNP) at 30 days.

Detailed Description
-----------------
Secondary objectives are: A. To assess the effect of therapeutic management guided by pulmonary ultrasound and inferior vena cava assessment on the risk of cardiovascular death and hospitalization for heart failure at 30 days. B. Describe the proportion of ultrasound congestion (pulmonary and inferior vena cava data) in patients free from clinical congestion at baseline in the intervention group and in all patients at D30 visit. C. Evaluate the association of ultrasound congestion (pulmonary and inferior vena cava assessment) with serum concentrations of natriuretic peptides at baseline and D30 visit. D. Evaluate the association of variations in ultrasound congestion (pulmonary and evaluation of the inferior vena cava) and variations in natriuretic peptides between baseline and D30 visit. E. Compare the proportion of ultrasound and clinical congestion in patients in the intervention group and in the control group at baseline and on D30 visit.

Official Title
-----------------
Impact of Ultrasound-guided Therapeutic Management of Ambulatory Patients With Heart Failure : An Open-label Randomized Clinical Trial

Conditions
-----------------
Heart Failure

Intervention / Treatment
-----------------
* Procedure: An ultrasound (lung and inferior vena cava) will be performed and the heart failure treatments will be guided by the results of the lung ultrasound and the evaluation of the inferior vena cava.
* Procedure: Usual care without ultrasound guidance


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female aged 18 and over Heart failure (regardless of left ventricular ejection fraction) Diagnosis of heart failure established more than 3 months ago Absence of significant clinical signs of congestion on clinical examination (absence of crackles and lower limbs oedema greater than perimalleolar oedema) Affiliation to social security Receiving complete information about research organization and signed informed consent. Exclusion Criteria: Natriuretic peptides result, carried out during the previous 30 days, available at the inclusion consultation Pulmonary or pleural pathology preventing reliable acquisition of lung ultrasound images: severe emphysema, chronic pleurisy, pulmonary fibrosis. Suspicion of cardiac amyloidosis or proven amyloidosis, Patient with severe primary heart valve disease Pregnant woman, parturient or nursing mother Adult person subject to a legal protection measure (guardianship, curatorship, safeguard of justice) Person deprived of liberty by a judicial or administrative decision, Person subject to psychiatric care pursuant to Articles L. 3212-1 and L. 3213-1 of the Public Health Code.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional group<br>The heart failure treatments will be guided by the results of the lung ultrasound and the evaluation of the inferior vena cava | Procedure: An ultrasound (lung and inferior vena cava) will be performed and the heart failure treatments will be guided by the results of the lung ultrasound and the evaluation of the inferior vena cava.<br>* An ultrasound (lung and inferior vena cava) will be performed and the heart failure treatments will be guided by the results of the lung ultrasound and the evaluation of the inferior vena cava. The choice of congestion treatment modalities to be implemented is left to the investigators' discretion, in accordance with European practice guidelines.<br>|
| Other: Control group<br>Usual care (i.e. without ultrasound guidance) will be provided. | Procedure: Usual care without ultrasound guidance<br>* Usual care (i.e. without ultrasound guidance)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death within 30 days (composite endpoint) | The primary endpoint will rank patients from worst to most favourable outcome during the trial. It will be a hierarchical composite of events as described by Felker in 2010 (PMID 20841546). | Within 30 days | 
| Hospitalization for heart failure within 30 days (composite endpoint) | The primary endpoint will rank patients from worst to most favourable outcome during the trial. It will be a hierarchical composite of events as described by Felker in 2010 (PMID 20841546). | Within 30 days | 
| Changes in N-terminal pro b-type natriuretic peptide (NtProBNP) between randomization and D30 (composite endpoint) | The primary endpoint will rank patients from worst to most favourable outcome during the trial. It will be a hierarchical composite of events as described by Felker in 2010 (PMID 20841546). | Between randomization and Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular death | Within the combined outcome of CV death or hospitalization for heart failure. Outcomes will be adjudicated blinded from randomization arm | Within 30 days | 
| Ultrasound pulmonary congestion defined ≥3 B-lines on two intercostal spaces bilaterally (8-point method) and systemic congestion defined as an inferior vena cava diameter 21 mm or greater and/or a low variation during the respiratory cycle |  | At baseline in the intervention group and in all patients at Day 30 post inclusion | 
| Circulating levels of natriuretic peptides (NtProBNP) |  | At baseline and Day 30 | 
| Changes in natriuretic peptides (NtProBNP) |  | Between baseline and Day 30. | 
| Ultrasound congestion defined as in B / and clinical congestion evaluated according to the EVEREST and ASCEND scores |  | At baseline in the intervention group and in all patients at the Day 30. |