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Lung Water by Ultrasound Guided Treatment in Hemodialysis Patients (The Lust Study). (LUST)

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ClinicalTrials.gov Identifier: NCT02310061
Recruitment Status : Completed
First Posted : December 5, 2014
Last Update Posted : May 7, 2021
Sponsor:
Collaborators:
Azienda Ospedaliera Bianchi-Melacrino-Morelli
Universität des Saarlandes
Dr. C.I. Parhon Hospital, Iasi
Medical University of Silesia
Hospital Universitari de Bellvitge
INSERM CHU de Nancy
University Hospital, Strasbourg
Shaare Zedek Medical Center
University Medical Centre Maribor
IASIO Hospital - General Clinic of Kallithea
ASL Parma
University Hospital, Ioannina
Wroclaw Medical University
C.T.M.R. Saint-Augustin
Hospital Ambroise Paré Paris
Centre Hospitalier F.H. Manhès
Aristotle University Of Thessaloniki
Università degli Studi di Ferrara
Istituto di Fisiologia Clinica CNR
Information provided by (Responsible Party):
Carmine Zoccali, Istituto di Fisiologia Clinica CNR

Brief Summary:

Volume overload is a leading risk factor for death and cardiovascular events in end stage renal disease patients maintained on chronic dialysis, particularly in those with myocardial ischemia and heart failure which represent a substantial fraction of this population. Early identification of volume overload may prevent cardiovascular sequel in these patients but clinical signs of volume expansion are unsatisfactory to reliably identify patients at risk and to monitor them over time. On the other hand, however reliable, standard techniques for measuring extracellular or circulating (blood) volume do not convey information on fundamental heart function parameters that determine the individual haemodynamic tolerance to volume excess and the response to ultrafiltration, i.e. left ventricular (LV) filling pressure and LV function.

Extra-vascular lung water is critically dependent on these parameters and represents a proxy of both, circulating volume and LV filling pressure and function, and may therefore be a better criterion to identify patients at a higher risk of volume-dependent adverse clinical outcomes and to monitor the effect of therapy aimed at preventing these outcomes. A fast (< 5 min.), easy to learn, simple and non-expensive technique which measures extra-vascular lung water by using standard ultrasound (US) machines has been validated in dialysis patients. Whether systematic measurement of lung water by this technique may translate into better clinical outcomes in End Stage Renal Disease (ESRD) patients has never been tested.

The aim of this randomized clinical trial is that of testing a treatment policy guided by extra-vascular lung water measurements by ultrasound to prevent all-cause death, decompensated heart failure and non-fatal myocardial infarction in high risk dialysis patients with myocardial ischemia (a history of myocardial infarction with or without ST elevation or unstable angina, acute coronary syndrome documented by ECG recordings and cardiac troponins or stable angina pectoris with documented coronary artery disease by prior coronary angiography or ECG) or overt heart failure (NYHA class III-IV).


Condition or disease Intervention/treatment Phase
Kidney Failure, Chronic Procedure: Extra-vascular lung water measurements by ultrasound (LW-US) Other: Standard protocol of fluid management in hemodialysis Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 383 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Lung Water By Ultra-Sound Guided Treatment To Prevent Death and Cardiovascular Complications in High Risk End Stage Renal Disease Patients With Cardiomyopathy (Lust Study)
Actual Study Start Date : March 2013
Actual Primary Completion Date : December 2019
Actual Study Completion Date : July 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Control arm
Standard protocol of fluid management in hemodialysis
Other: Standard protocol of fluid management in hemodialysis
The intervention consists in applying a standard clinical approach for monitoring/tailoring fluid excess in HD patients.

Experimental: Active arm
Extra-vascular lung water measurements by ultrasound (LW-US)
Procedure: Extra-vascular lung water measurements by ultrasound (LW-US)
It is widely agreed that the high prevalence of patients with LV dysfunction and heart failure and the lack of simple, non-expensive, bedside techniques that may serve to estimate and monitor parameters of central hemodynamics for guiding the prescription of ultrafiltration (UF) and drug treatment is a factor of major clinical relevance. So,in patients allocated to the active arm, nephrologists register pre- and post-dialysis US-B lines whenever considered useful for volume monitoring.
Other Name: LW-US




Primary Outcome Measures :
  1. Cumulative incidence of the composite outcome "death, myocardial infarction, heart failure". [ Time Frame: All events occurred during 24 months of follow up will be assessed at 2 years after the start of the study. For Time-to-Event analyses, we will consider the time from the first visit to the first occurrence of death, or MI or heart failure. ]

    Myocardial infarction and heart failure will be defined on the basis of international standard protocols.

    - The following figures we expect to occur in the two study arms:

    Active arm: 30% Control arm: 45%



Secondary Outcome Measures :
  1. All-cause hospitalizations [ Time Frame: First occurrence of all-cause hospitalization over a follow-up period of 24 months ]
    Hospitalizations due to any cause

  2. Cardiovascular hospitalizations [ Time Frame: First occurrence of cardiovascular hospitalization over a follow-up period of 24 months ]
    All cardiovascular events requiring hospitalization

  3. Left ventricular mass index (LVMI) [ Time Frame: LVMI will be measured by cardiologists at baseline, 6, 12 and 24 months ]

    LVMI will be measured by Echocardiography.

    We expect the following changes in LVMI between the two study arms:

    Active arm: - 2±11 Control arm: 3±11


  4. Left ventricular ejection fraction (LVEF) [ Time Frame: LVEF will be measured by cardiologists at baseline, 6, 12 and 24 months ]

    Left ventricular ejection fraction will be measured by Echocardiography.

    We expect the following changes in LVEF between the two study arms:

    Active arm: 3±9% Control arm: 0±9%


  5. Diastolic function. [ Time Frame: Diastolic function (E/E') will be measured by cardiologists at baseline, 6, 12 and 24 months ]

    Diastolic function will be assessed by Echocardiography.

    We expect the following changes in E/E' between the two study arms:

    Active arm: -2±6 Control arm: 0±6


  6. Left atrial volume [ Time Frame: Left atrial volume (LAV) will be measured by cardiologists at baseline, 6, 12 and 24 months ]

    Left atrial volume will be measured by Echocardiography.

    We expect the following changes in LAV between the two study arms:

    Active arm: -2±17 Control arm: 4±17



Other Outcome Measures:
  1. Patients who die of any cause during the follow-up [ Time Frame: All deaths occuring over a follow-up period of 24 months ]
    Death due to any cause

  2. Patients who develop myocardial infarction during the follow-up [ Time Frame: First myocardial infarction occuring over a follow-up period of 24 months ]
    Myocardial infarction as defined according to international standard.

  3. Patients who develop episodes of decompensated heart failure during the follow-up [ Time Frame: First heart failure occuring over a follow-up period of 24 months ]
    Heart failure as defined according to international standard.

  4. Total number of recurrent episodes of decompensated heart failure [ Time Frame: All heart failure episodes occuring over a follow-up period of 24 months ]
    Heart failure as defined according to international standard.

  5. Total number of recurrent cardiovascular events [ Time Frame: All cardiovascular events events occuring over a follow-up period of 24 months ]
    All cardiovascular events as defined according to international standard.

  6. Analysis of hypotension episodes [ Time Frame: All hypotension episodes occuring over a follow-up period of 24 months ]
    All hypotension episodes

  7. Correlation between repeated measurements of lung comets (by US-B lines) and the combined outcome [ Time Frame: All combined outcomes (death, myocardial infarction, decompensated heart failure) occuring over a follow-up period of 24 months ]
    Analysis by joint models combining linear mixed models and survival analysis

  8. Correlation between repeated measurements of lung comets (by US-B lines) and all cause mortality [ Time Frame: All deaths occuring over a follow-up period of 24 months ]
    Analysis by joint models combining linear mixed models and survival analysis

  9. Correlation between repeated measurements of lung comets (by US-B lines) and myocardial infarction [ Time Frame: First myocardial infarction occuring over a follow-up period of 24 months ]
    Analysis by joint models combining linear mixed models and survival analysis

  10. Correlation between repeated measurements of lung comets (by US-B lines) and decompensated heart failure [ Time Frame: First episode of heart failure occuring over a follow-up period of 24 months ]
    Analysis by joint models combining linear mixed models and survival analysis

  11. Correlation between repeated measurements of lung comets (by US-B lines) and Left Ventricular Mass Index (LVMI) [ Time Frame: LVMI will be measured by cardiologists at baseline, 6, 12 and 24 months ]
    Analysis by linear mixed models

  12. Correlation between repeated measurements of lung comets (by US-B lines) and Left Ventricular Ejection Fraction (LVEF) [ Time Frame: LVEF will be measured by cardiologists at baseline, 6, 12 and 24 months ]
    Analysis by linear mixed models

  13. Correlation between repeated measurements of lung comets (by US-B lines) and Diastolic Function (E/E') [ Time Frame: E/E' will be measured by cardiologists at baseline, 6, 12 and 24 months ]
    Analysis by linear mixed models

  14. Correlation between repeated measurements of lung comets (by US-B lines) and Left Atrial Volume (LAV) [ Time Frame: LAV will be measured by cardiologists at baseline, 6, 12 and 24 months ]
    Analysis by linear mixed models

  15. Effect of allocation arm on Sleep Quality [ Time Frame: Sleep quality will be assessed at baseline, 6, 12 and 24 months ]
    Analysis by linear mixed models of the effect of allocation arm on Sleep Quality assessed by Berlin Questionnaire

  16. Effect of allocation arm on Quality of Life [ Time Frame: Quality of life will be assessed at baseline, 6, 12 and 24 months ]
    Analysis by linear mixed models of the effect of allocation arm on Quality of life assessed by by Short Form health survey (SF36)

  17. Effect of allocation arm on Depression [ Time Frame: Depression will be assessed at baseline, 6, 12 and 24 months ]
    Analysis by linear mixed models of the effect of allocation arm on Depression assessed by Center for Epidemiologic Studies - Depression Scale (CES-D)

  18. Effect of allocation arm on overall performance [ Time Frame: Performance will be assessed at baseline, 6, 12 and 24 months ]
    Analysis by linear mixed models of the effect of allocation arm on overall performance assessed by Karnofsky performance score

  19. Effect of allocation arm on Nutritional Status [ Time Frame: Nutritional Status will be assessed by at baseline, 6, 12 and 24 months ]
    Analysis by linear mixed models of the effect of allocation arm on nutritional status assessed by Subjective Global Assessment (SGA)

  20. Analysis of repeated measurements of lung comets (by US-B lines) over time assessed pre-dialysis [ Time Frame: All lung comets measured pre-dialysis over a follow-up period of 24 months ]
    Pre-dialysis lung comets changes and study outcomes

  21. Analysis of repeated measurements of lung comets (by US-B lines) over time assessed post-dialysis [ Time Frame: All lung comets measured post-dialysis over a follow-up period of 24 months ]
    Post-dialysis lung comets changes and study outcomes



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 18 years
  • Dialysis vintage > 3 months
  • A history of myocardial infarction with or without ST elevation or unstable angina, acute coronary syndrome, documented by ECG recordings and cardiac troponins, or stable angina pectoris with documented coronary artery disease by prior coronary angiography or ECG or dyspnoea class III-IV NYHA
  • Written consent to take part in the study

Exclusion Criteria:

  • Cancer or other advanced non cardiac disease or comorbidity (e.g. end-stage liver failure) imposing a very poor short-term prognosis
  • Active infections or relevant inter-current disease
  • Inadequate lung scanning and echocardiographic studies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02310061


Locations
Show Show 19 study locations
Sponsors and Collaborators
Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy
Azienda Ospedaliera Bianchi-Melacrino-Morelli
Universität des Saarlandes
Dr. C.I. Parhon Hospital, Iasi
Medical University of Silesia
Hospital Universitari de Bellvitge
INSERM CHU de Nancy
University Hospital, Strasbourg
Shaare Zedek Medical Center
University Medical Centre Maribor
IASIO Hospital - General Clinic of Kallithea
ASL Parma
University Hospital, Ioannina
Wroclaw Medical University
C.T.M.R. Saint-Augustin
Hospital Ambroise Paré Paris
Centre Hospitalier F.H. Manhès
Aristotle University Of Thessaloniki
Università degli Studi di Ferrara
Istituto di Fisiologia Clinica CNR
Investigators
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Principal Investigator: Carmine Zoccali, Prof CNR-IBIM and Nephrology Unit, Reggio Calabria
Publications:

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Responsible Party: Carmine Zoccali, MD, FASN, Professor of Nephrology (PG), Istituto di Fisiologia Clinica CNR
ClinicalTrials.gov Identifier: NCT02310061    
Other Study ID Numbers: ERA-EDTA-01062012
First Posted: December 5, 2014    Key Record Dates
Last Update Posted: May 7, 2021
Last Verified: May 2021
Keywords provided by Carmine Zoccali, Istituto di Fisiologia Clinica CNR:
Dialysis
ESRD
lung congestion
heart failure
LW-US
Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Failure, Chronic
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic