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

NCT02310061 | Completed DMC

• 1 other identifier: ERA-EDTA-01062012
• Study Type: interventional
• Target: 383
• Locations: 9 countries
• Sites: 19

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).

Conditions

Kidney Failure, Chronic

Keywords

Dialysis; ESRD; lung congestion; heart failure; LW-US

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of the composite outcome "death, myocardial infarction, 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%

  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.

Secondary Outcomes (6)

• All-cause hospitalizations

  First occurrence of all-cause hospitalization over a follow-up period of 24 months

• Cardiovascular hospitalizations

  First occurrence of cardiovascular hospitalization over a follow-up period of 24 months

• Left ventricular mass index (LVMI)

  LVMI will be measured by cardiologists at baseline, 6, 12 and 24 months

• Left ventricular ejection fraction (LVEF)

  LVEF will be measured by cardiologists at baseline, 6, 12 and 24 months

• Diastolic function.

  Diastolic function (E/E') will be measured by cardiologists at baseline, 6, 12 and 24 months

Other Outcomes (23)

• Patients who die of any cause during the follow-up

  All deaths occuring over a follow-up period of 24 months

• Patients who develop myocardial infarction during the follow-up

  First myocardial infarction occuring over a follow-up period of 24 months

• Patients who develop episodes of decompensated heart failure during the follow-up

  First heart failure occuring over a follow-up period of 24 months

Study Arms (2)

Control arm

PLACEBO COMPARATOR

Standard protocol of fluid management in hemodialysis

Other: Standard protocol of fluid management in hemodialysis

Active arm

EXPERIMENTAL

Extra-vascular lung water measurements by ultrasound (LW-US)

Procedure: Extra-vascular lung water measurements by ultrasound (LW-US)

Interventions

Extra-vascular lung water measurements by ultrasound (LW-US) PROCEDURE

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.

Also known as: LW-US

Active arm

Standard protocol of fluid management in hemodialysis OTHER

The intervention consists in applying a standard clinical approach for monitoring/tailoring fluid excess in HD patients.

Control arm

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy: lead
• Azienda Ospedaliera Bianchi-Melacrino-Morelli: collaborator
• Universität des Saarlandes: collaborator
• Dr. C.I. Parhon Hospital, Iasi: collaborator
• Medical University of Silesia: collaborator
• Hospital Universitari de Bellvitge: collaborator
• Central Hospital, Nancy, France: collaborator
• University Hospital, Strasbourg: collaborator
• Shaare Zedek Medical Center: collaborator
• University Medical Centre Maribor: collaborator
• IASIO Hospital - General Clinic of Kallithea: collaborator
• ASL Parma: collaborator
• University Hospital, Ioannina: collaborator
• Wroclaw Medical University: collaborator
• C.T.M.R. Saint-Augustin: collaborator
• Hospital Ambroise Paré Paris: collaborator
• Centre Hospitalier FH Manhes: collaborator
• Aristotle University Of Thessaloniki: collaborator
• Università degli Studi di Ferrara: collaborator
• Istituto di Fisiologia Clinica CNR: collaborator

Study Sites (19)

C.T.M.R. Saint Augustin

Bordeaux, France

Location

Hôpital Ambroise Paré (Assistance-Publique Hôpitaux de Paris)

Boulogne-Billancourt, France

Location

Hôpital F.H. Manhès

Fleury-Mérogis, France

Location

ALTIR - INSERM CHU de Nancy

Nancy, France

Location

University Hospital Strasbourg

Strasbourg, France

Location

Saarland University Medical Centre

Homburg/Saar, Germany

Location

IASIO Hospital - General Clinic of Kallithea

Athens, Greece

Location

University Hospital of Ioannina

Ioannina, Greece

Location

Aristotle University

Thessaloniki, Greece

Location

Shaare Zedek Medical Center

Jerusalem, Israel

Location

CNR Institute of Clinical Physiology

Pisa, PI, 56100, Italy

Location

CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension Unit

Reggio Calabria, RC, 89100, Italy

Location

University of Ferrara

Ferrara, Italy

Location

ASL Parma

Parma, Italy

Location

Medical University of Silesia in Katowice

Katowice, Poland

Location

Medical University

Wroclaw, Poland

Location

University Hospital 'Dr C.I. Parhon'

Iași, Romania

Location

University Clinical Centre

Maribor, Slovenia

Location

Bellvitge's University Hispital

Barcelona, Spain

Location

Related Publications (11)

• Kramer A, Stel V, Zoccali C, Heaf J, Ansell D, Gronhagen-Riska C, Leivestad T, Simpson K, Palsson R, Postorino M, Jager K; ERA-EDTA Registry. An update on renal replacement therapy in Europe: ERA-EDTA Registry data from 1997 to 2006. Nephrol Dial Transplant. 2009 Dec;24(12):3557-66. doi: 10.1093/ndt/gfp519. Epub 2009 Oct 9.

  PMID: 19820003 BACKGROUND

• Charra B, Calemard E, Ruffet M, Chazot C, Terrat JC, Vanel T, Laurent G. Survival as an index of adequacy of dialysis. Kidney Int. 1992 May;41(5):1286-91. doi: 10.1038/ki.1992.191.

  PMID: 1614043 BACKGROUND

• Sinha AD, Agarwal R. Can chronic volume overload be recognized and prevented in hemodialysis patients? The pitfalls of the clinical examination in assessing volume status. Semin Dial. 2009 Sep-Oct;22(5):480-2. doi: 10.1111/j.1525-139X.2009.00641.x. Epub 2009 Sep 9. No abstract available.

  PMID: 19744155 BACKGROUND

• Staub NC. Pulmonary edema. Physiol Rev. 1974 Jul;54(3):678-811. doi: 10.1152/physrev.1974.54.3.678. No abstract available.

  PMID: 4601625 BACKGROUND

• Crandall ED, Staub NC, Goldberg HS, Effros RM. Recent developments in pulmonary edema. Ann Intern Med. 1983 Dec;99(6):808-22. doi: 10.7326/0003-4819-99-6-808.

  PMID: 6360001 BACKGROUND

• Jambrik Z, Monti S, Coppola V, Agricola E, Mottola G, Miniati M, Picano E. Usefulness of ultrasound lung comets as a nonradiologic sign of extravascular lung water. Am J Cardiol. 2004 May 15;93(10):1265-70. doi: 10.1016/j.amjcard.2004.02.012.

  PMID: 15135701 BACKGROUND

• Picano E, Gargani L, Gheorghiade M. Why, when, and how to assess pulmonary congestion in heart failure: pathophysiological, clinical, and methodological implications. Heart Fail Rev. 2010 Jan;15(1):63-72. doi: 10.1007/s10741-009-9148-8.

  PMID: 19504345 BACKGROUND

• Picano E, Frassi F, Agricola E, Gligorova S, Gargani L, Mottola G. Ultrasound lung comets: a clinically useful sign of extravascular lung water. J Am Soc Echocardiogr. 2006 Mar;19(3):356-63. doi: 10.1016/j.echo.2005.05.019.

  PMID: 16500505 BACKGROUND

• Agricola E, Bove T, Oppizzi M, Marino G, Zangrillo A, Margonato A, Picano E. "Ultrasound comet-tail images": a marker of pulmonary edema: a comparative study with wedge pressure and extravascular lung water. Chest. 2005 May;127(5):1690-5. doi: 10.1378/chest.127.5.1690.

  PMID: 15888847 BACKGROUND

• Mallamaci F, Benedetto FA, Tripepi R, Rastelli S, Castellino P, Tripepi G, Picano E, Zoccali C. Detection of pulmonary congestion by chest ultrasound in dialysis patients. JACC Cardiovasc Imaging. 2010 Jun;3(6):586-94. doi: 10.1016/j.jcmg.2010.02.005.

  PMID: 20541714 BACKGROUND

• Cice G, Ferrara L, Di Benedetto A, Russo PE, Marinelli G, Pavese F, Iacono A. Dilated cardiomyopathy in dialysis patients--beneficial effects of carvedilol: a double-blind, placebo-controlled trial. J Am Coll Cardiol. 2001 Feb;37(2):407-11. doi: 10.1016/s0735-1097(00)01158-x.

  PMID: 11216954 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic; Heart Failure

Interventions

Renal Dialysis

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Sorption Detoxification

Study Officials

• Carmine Zoccali, Prof

  CNR-IBIM and Nephrology Unit, Reggio Calabria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FASN, Professor of Nephrology (PG)

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: December 5, 2014
• Study Start: March 1, 2013
• Primary Completion: December 1, 2019
• Study Completion: July 1, 2020
• Last Updated: March 14, 2023

Record last verified: 2023-03

Locations

DE (1); IT (4); PL (2); ES (1); IL (1); SL (1); GR (3); FR (5); RO (1)