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Critical IllnessDYNAMICNCT04584203

Diastolic dYsfunctioN AssessMent in critICally Ill Patients

An observational study of Critical Illness and Diastolic Dysfunction, run by Humanitas Clinical and Research Center at 8 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The role of the left ventricular diastolic function (LVDD) in the weaning failure from mechanical ventilation in unclear. Specifically, is unclear whether the outcome of the weaning process could be affected by a pre-existing LVDD (before ICU admission), or by the worsening of a chronic pattern, or by a de-novo LVDD… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bedside Echocardiography, Spontaneuos breathing trial and Bedside Echocardiography_1
Type of treatment
Surgery or procedure
How many people
297 participants
Where
8 sitesItaly
Study dates
1 Jun 2021to 1 Jun 2022
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Critically ill patients admitted to General ICU

Who may be able to join

  • Expected to be ventilated for >48 hours
  • Age > 50

Who cannot join

  • Atrial fibrillation (at the admission or during ICU stay);
  • Neuromuscular disorders
  • •. Severe neurological events (traumatic or not) with GCS < 8 at admission
  • Home ventilation prior to admission;
  • Palliative intubation;
  • Intubation for an indication to tracheostomy;
  • Poor acoustic window (after the first assessment);
  • Severe mitral and/or aortic valve stenosis or regurgitation.

Trial locations and contacts

8 sites in 1 country.

Antonio Messina, PhD contact

+390282241

antonio.messina@humanitas.it

8 sites in 1 country

Italy8 sites, 8 recruiting
  • Ospedale Ss. Trinità

    Borgomanero, Novara, 28100

    DAvide Colombo

    Not yet recruiting
  • "Policlinico-San Marco"

    Catania

    Filippo Sanfilippo

    Not yet recruiting
  • Careggi University Hospital

    Florence, Tuscany, 50134

    Stefano Romagnoli, MD, +39 055 794111, stefano-romagnoli@hotmail.com

    Not yet recruiting
  • Azienda Ospedaliera di Perugia

    Perugia

    Gianmaria Cammarota

    Not yet recruiting
  • Grande Ospedale Metropolitano

    Reggio Calabria

    Marco Tescione

    Not yet recruiting
  • Policlinico Universitario A. Gemelli

    Roma

    Antonio Dell'anna

    Not yet recruiting
  • Humanitas Research Hospital

    Rozzano, Milano, 20089

    Antonio Messina, MD, +390282241, antonio.messina@humanitas.it

    Antonio Messina, MD, +3902822414131, mess81rc@gmail.com

    Recruiting
  • Azienda Sanitaria Universitaria Integrata di Udine

    Udine

    Luigi Vetrugno

    Not yet recruiting

Other trials in Italy

About this study

Official title: Diastolic dYsfunctioN AssessMent in critICally Ill Patients: an Observational Prospective Multicentric Study.

The role of the left ventricular diastolic function (LVDD) in the weaning failure from mechanical ventilation in unclear. Specifically, is unclear whether the outcome of the weaning process could be affected by a pre-existing LVDD (before ICU admission), or by the worsening of a chronic pattern, or by a de-novo LVDD presentation.

Read the detailed description

Bedside echocardiography plays a critical diagnostic role in patients with heart failure, being other examinations (i.e., physical examination, electrocardiogram, and chest radiograph) unable to provide key information to discriminate between diastolic and systolic heart failure. Transthoracic echocardiography (TTE) can assess diastolic function by means of the doppler filling pattern, and can non-invasively measure intracardiac pressure at the bedside.

During sinus rhythm, diastolic flow shows the E and A waves, which reflects early diastolic filling and atrial contraction in the late diastole, respectively. Velocity of blood flow across the mitral valve depends on the trans-mitral pressure gradient; then, E-wave velocity is influenced both by the rate of early diastolic relaxation and by the left atrial pressure. Changes of the velocity pattern can suggest left ventricular diastolic function (LVDD) and prognosis, although mitral inflow patterns are highly susceptible to loading conditions (mainly left atrial pressure). LVDD is quite is a condition quite common in the population. A cross-sectional survey of over 2000 randomly selected Minnesota residents aged 45 years or older found an incidence of LVDD almost five times higher than LV systolic dysfunction (28% vs. 6%, respectively), which was a strong predictor of mortality (hazard ratio ranging from 8.3 for mild LVDD to 10.2 for at-least-moderate LVDD).

In a randomly recruited population sample (n = 539; 50.5% women; mean age, 52.5 years), the prevalence of the LVDD in those patients older than 50 y.o. was of about 50%5.

Doppler echocardiography could be a noninvasive tool for the detection of weaning-induced left ventricular filling pressure elevation. Transmitral flow can help measure peak Doppler velocities of E and A waves. E/A ratio has been proposed to estimate the left ventricular filling pressure. Tissue Doppler imaging can measure early diastolic mitral annular velocity (E'), which is a load-independent indicator of myocardial relaxation. The combination of tissue Doppler imaging and pulsed Doppler transmitral flow can allow the computation of the E/E' ratio, which is one of the best echocardiographic estimate of left ventricular filling pressure.

The role of LVDD in critically ill patients is probably greatly underestimated by intensivists, probably because in the past diastolic function was difficult to evaluate at the bedside6. The LVDD in intensive care unit (ICU) patients can affect the outcome of weaning from mechanical ventilation, especially in septic patients. In fact, cardiogenic pulmonary edema has been recognized as a highly incident cause of weaning failure. Unsuccessful weaning from mechanical ventilation occurs in approximately 20% of patients and is related to prolonged mechanical ventilation, length of stay in the intensive care unit, and increased morbidity and mortality. It has been proved that a spontaneous breathing trial (SBT) increases the left ventricular filling pressure, leading to cardiogenic pulmonary edema and impaired gas exchange.

However, studies focused on the impact of that medical condition on weaning showed conflicting results. Moreover, heterogeneous definitions and measurements of LVDD have been provided, associated to different form of SBTs. Furthermore, the majority carried out a cross-sectional assessment of the LVDD before and after the SBT, not including changes in the diastolic function during the ICU stay. All these variables limit the comparability and the clinical applications of these studies.

Moreover, LV diastolic function depends on myocardial relaxation, LV stiffness, and filling pressures, which are frequently impaired during the ICU stay (e.g., progression of the disease, volume resuscitation, positive end-expiratory pressure, administration of inotropes, vasopressors, etc). It is still uncertain whether the SBT failure could be affected by pre-existing conditions (i.e. a LVDD present at the ICU admission) or by a worsening of the cardiac function after the ICU admission.

As a matter of fact, the assessment of LVDD at the bedside is not routinely performed before the SBT and the role of the degree of the LVDD in still not defined. Moreover, it unclear whether the outcome of the weaning process could be affected by a pre-existing LVDD (before ICU admission), or by the worsening of a chronic pattern, or by a de-novo LVDD presentation.

Being tested
Bedside Echocardiography, Spontaneuos breathing trial, Bedside Echocardiography_1, Bedside Echocardiography_2, Bedside Echocardiography_3
Medical subject headings
Critical Illness, Heart Failure, Diastolic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bedside EchocardiographyDiagnostic test

    All the intensivists performing the TTE in the involved centers fulfill the criteria of the American Society of Echocardiography and of the European Society of Intensive Care.

    Medicine to be considered as experts in critical care echocardiography. Each center performs the TTE evaluation by means of the ultrasound device available in the unit equipped with the tissue Doppler imaging program and a phased array transducer of 2.5 MHz and doppler signals is recorded along with the electrocardiogram.

    For the purpose of this study, the following TTE parameters are recorded from the apical 4-chamber view during each set of measurements:

  • Spontaneuos breathing trialProcedure or surgery

    The Spontaneous Breathing Trial will be performed accordingly to the clinical practice of the involved centers (a total support - including positive end-expiratory pressure plus pressure support equal or lower to 8 cmH20)

  • Bedside Echocardiography_1Diagnostic test

    Also called Baseline Echo_1

    Echocardiography performed within 24h from patient's admission - not optional

  • Bedside Echocardiography_2Diagnostic test

    Also called Echo_2

    Echocardiography performed within 12h from patient's spontaneous breathing trial - not optional

  • Bedside Echocardiography_3Diagnostic test

    Also called Echo_3

    Echocardiography performed at 60 +/- 12h from patient's admission - optional

  • Bedside Echocardiography_4Diagnostic test

    Also called Echo_4

    Echocardiography performed 24h after patient's estubation - optional

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Spontaneous breathing trial failure

    Patients admitted with LVDD

    Measured: 6 hour after Spontaneous breathing trial end

  2. Spontaneous breathing trial failure

    Patients worsening a pre-existing LVDD or developing a LVDD during the ICU stay.

    Measured: 6 hour after Spontaneous breathing trial end

Secondary outcomes (3)
  1. Prevalence of LVDD in critically ill patients

    Echocardiography measurements

    Measured: up to 3 weeks

  2. To assess the degree of the LVDD in critically ill patients

    Echocardiography measurements

    Measured: up to 3 weeks

  3. To correlate LVDD with clinical outcomes

    Echocardiography measurements

    Measured: up to 3 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Oct 2020
  2. Study start1 Jun 2021
  3. Primary completion1 Jun 2022 (estimated)
  4. Study completion1 Jun 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
297 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04584203
Sponsor's protocol ID
DYNAMIC
Acronym
DYNAMIC
Status last verified
Dec 2021
First submitted
24 Jul 2020
Last updated
3 Jan 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Raw data available from the PI, under reasonable reason

Publications

  • Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Popescu BA, Waggoner AD. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016 Apr;29(4):277-314. doi: 10.1016/j.echo.2016.01.011. No abstract available.

    PubMed 27037982
  • Schmidt GA, Girard TD, Kress JP, Morris PE, Ouellette DR, Alhazzani W, Burns SM, Epstein SK, Esteban A, Fan E, Ferrer M, Fraser GL, Gong MN, Hough CL, Mehta S, Nanchal R, Patel S, Pawlik AJ, Schweickert WD, Sessler CN, Strom T, Wilson KC, Truwit JD. Liberation From Mechanical Ventilation in Critically Ill Adults: Executive Summary of an Official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline. Chest. 2017 Jan;151(1):160-165. doi: 10.1016/j.chest.2016.10.037. Epub 2016 Nov 3.

    PubMed 27818329
  • Subira C, Hernandez G, Vazquez A, Rodriguez-Garcia R, Gonzalez-Castro A, Garcia C, Rubio O, Ventura L, Lopez A, de la Torre MC, Keough E, Arauzo V, Hermosa C, Sanchez C, Tizon A, Tenza E, Laborda C, Cabanes S, Lacueva V, Del Mar Fernandez M, Arnau A, Fernandez R. Effect of Pressure Support vs T-Piece Ventilation Strategies During Spontaneous Breathing Trials on Successful Extubation Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA. 2019 Jun 11;321(22):2175-2182. doi: 10.1001/jama.2019.7234.

    PubMed 31184740
  • de Meirelles Almeida CA, Nedel WL, Morais VD, Boniatti MM, de Almeida-Filho OC. Diastolic dysfunction as a predictor of weaning failure: A systematic review and meta-analysis. J Crit Care. 2016 Aug;34:135-41. doi: 10.1016/j.jcrc.2016.03.007. Epub 2016 Mar 16.

    PubMed 27067288
  • Vignon P. Ventricular diastolic abnormalities in the critically ill. Curr Opin Crit Care. 2013 Jun;19(3):242-9. doi: 10.1097/MCC.0b013e32836091c3.

    PubMed 23624639

Questions about this trial

What is this clinical trial studying?

An observational study of Critical Illness and Diastolic Dysfunction, run by Humanitas Clinical and Research Center at 8 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 3 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Antonio Messina, PhD (+390282241, antonio.messina@humanitas.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Spontaneous breathing trial failure (time frame: 6 hour after Spontaneous breathing trial end). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04584203, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2022.

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DYNAMIC Clinical Trial NCT04584203 | AzTrials